← Product Code MER · P250007 # Zenflow Spring® Implant and Delivery System (P250007) _Zenflow, Inc. · MER · Dec 11, 2025 · Gastroenterology, Urology · APPR_ **Canonical URL:** https://fda.innolitics.com/device/P250007 ## Device Facts - **Applicant:** Zenflow, Inc. - **Product Code:** MER - **Decision Date:** Dec 11, 2025 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Gastroenterology, Urology - **Attributes:** Therapeutic ## Indications for Use The Zenflow Spring Implant and Delivery System is indicated for the treatment of obstructive lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) in men with prostatic urethral lengths between 25 and 45 mm and prostate volumes between 25 and 80 cc. ## Device Story Zenflow Spring Implant is a permanent, removable nitinol wire-strand implant designed to treat BPH-related LUTS. The system includes a delivery catheter with a compliant balloon anchor and a handle with a trigger mechanism for implant deployment/retraction. Used in a clinic or hospital setting by a urologist under fluoroscopic guidance. The implant is placed in the prostatic urethra to provide mechanical support, relieving obstruction. The physician uses the delivery system to position the implant; the balloon anchors the device at the bladder neck during deployment. The implant is designed to be retrieved if necessary. The device benefits patients by improving urinary flow and reducing symptoms without the need for permanent tissue ablation or resection, preserving sexual function. ## Clinical Evidence Pivotal BREEZE study (IDE G210096) was a prospective, multi-center, 2:1 randomized, sham-controlled trial (n=231). Primary endpoints were 30% IPSS improvement at 3 months and mean percent change in IPSS at 12 months. In the mITT/IU population (n=109 treatment, n=57 sham), the treatment arm showed statistically significant improvement in IPSS responder rates at 3 months (59.6% vs 33.3%) and a mean IPSS reduction of 37.2% at 12 months. No device-related SAEs reported through 12 months. Common AEs included dysuria and painful ejaculation. Bench testing and animal studies supported biocompatibility and mechanical integrity. ## Technological Characteristics Implant: Electropolished, passivated nitinol (nickel-titanium alloy) wire strand, ring elements with spine sections, 15-21 mm length. Delivery System: 11.5 Fr catheter, compliant balloon anchor, trigger-actuated deployment. Sterilization: Ethylene Oxide (SAL 10^-6). Connectivity: None. Software: None (mechanical device). Standards: ISO 10993-1, ISO 14971, ASTM F2182-19, ASTM F2119-24, ASTM F2052-21, ISO 25539-2, ASTM F2477, ASTM F2129. ## Reference Devices - Spring Scope ([K251140](/device/K251140.md)) - Camera Control Unit ([K251140](/device/K251140.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name Stent, Urethral, Prostatic, Permanent Or Semi-Permanent Device Trade Name Zenflow Spring® Implant and Delivery System Device Product Code MER Company Name and Address Zenflow, Inc. 395 Oyster Point Blvd., Suite 501 South San Francisco, CA 94080 Date of Panel Recommendation None PMA Number P250007 Date of FDA Notice of Approval December 11, 2025 II. INDICATIONS FOR USE The Zenflow Spring Implant and Delivery System is indicated for the treatment of obstructive lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) in men with prostatic urethral lengths between 25 and 45 mm and prostate volumes between 25 and 80 cc. III. CONTRAINDICATIONS - Patients with a previous laser prostatectomy, hyperthermia, brachytherapy, or invasive treatment to the prostate or pelvis area - Patients with acute urethral stricture disease, meatal stenosis, or bladder neck stricture – either current or recurrent - Patients with active urolithiasis - Prostate cancer or previous external or internal gamma radiation therapy for prostate or proximal urethral cancer - Known allergy to nickel, titanium, or stainless steel - Patients with urinary tract infections (UTIs) - Patients with acute infection (acute urethritis, acute prostatitis, acute epididymitis) - Patients with hematuria with an undiagnosed cause - Patients with an existing prostatic foreign body - Urinary incontinence due to an incompetent external sphincter PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {1} PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 2 of 47 # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Zenflow Spring® Implant and Delivery System labeling. # V. DEVICE DESCRIPTION The Zenflow Spring® System consists of the Spring Implant and Delivery System, Spring Scope, Camera Control Unit (CCU), and Implant Retrieval Device (IRD). The Spring Implant and Delivery System, Spring Scope, and Implant Retrieval Device, are packaged separately, supplied sterile, and indicated for single use only. The CCU is intended to be used outside the sterile field, supplied non-sterile, and can be reused for multiple procedures. Only the Spring Implant and Delivery System are the subject devices of this PMA. The Spring Scope and Camera Control Unit were cleared under K251140. ## Spring Implant The Spring Implant is an electropolished and passivated nickel titanium alloy (nitinol) implant. The implant is constructed from a single wire strand formed into ring elements connected by spine sections. Implant sizes range between 15 mm – 21 mm in length (as shown in Figure 1) to accommodate prostate lengths between 25 mm – 45 mm. The ends of the implant have rounded balls to assist in grasping the device. The device is designed to be removable and retrieved at any time after deployment. ![img-0.jpeg](img-0.jpeg) Figure 1. Zenflow Spring Implant Sizes (left to right 15/18/21 mm, not to scale) ## Delivery System As shown in Figure 2, the Zenflow Delivery System consists of a handle and a catheter shaft. The Spring Implant is designed to be straightened and to reside within a lumen of the 11.5 Fr Delivery System catheter for insertion. When inflated, a compliant balloon at the distal end of the catheter is designed to anchor and position the Delivery System during Implant delivery. {2} ![img-1.jpeg](img-1.jpeg) Figure 2. Labeled Zenflow Delivery System with Spring Implant | No. | Part | Function | | --- | --- | --- | | 1 | Balloon Inflation Port | Allows user to inflate balloon anchor. | | 2 | Trigger | Allows the user to deploy or retract the Implant. | | 3 | Handle | Allows user to grip and control the device. | | 4 | Directional Switch | Chooses whether Implant is deployed or retracted with each trigger pull. | | 5 | Unlock Knob | Allows the Implant to be released. | | 6 | Spring Implant (pre-attached but not loaded) | Implantable device | | 7 | Balloon (shown inflated) | Provides anchor on bladder neck during Implant delivery. | | 8 | Delivery System Shaft | Houses Implant during delivery and connects to handle. | | 9 | Abort Key | Pushes the recessed Abort Button. | | 10 | Abort Button (recessed) | Used if Delivery System is unable to advance or retract, leaving the implant partially deployed. | # VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the treatment of lower urinary tract symptoms (LUTS) attributed to BPH. According to the American Urological Association's (AUA) guidelines (1), these alternatives include: # Medical Therapy Medical therapy is typically the first treatment approach for BPH. Drug classes used to treat BPH include alpha blockers, 5-alpha reductase inhibitors, or a combination thereof, and phosphodiesterase-5 inhibitors. # Surgical Therapy Surgical interventions for BPH include transurethral resection of the prostate (TURP), prostatectomy, transurethral incision of the prostate (TUIP), transurethral vaporization of the prostate (TUVP), photoselective vaporization of the prostate (PVP), prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), laser enucleation, robotic waterjet PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {3} treatment (RWT), prostate artery embolization (PAE), and temporary and permanently implanted prostatic devices (TIPD). Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with their physician to select the method that best meets expectations and lifestyle. ## VII. MARKETING HISTORY The Zenflow Spring® Implant and Delivery System has not been marketed in the United States or any foreign country. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the Zenflow Spring Implant: - Dysuria - Hematuria - Urgency - Incontinence - Retention - Constipation - Nocturia - Bladder spasms - Back pain - Infection - Lower urinary tract system pain - Ejaculatory/sexual dysfunction or pain - Urethral stricture - Obstruction secondary to tissue in-growth For the specific adverse events that occurred in the clinical study, please see Section X below. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {4} IX. SUMMARY OF NON-CLINICAL STUDIES # A. Laboratory Studies # Biocompatibility The applicant completed a biological risk assessment for the Zenflow Spring® Implant and Delivery System per ISO 10993-1:2018 Biological Evaluation of Medical Devices – Part 1: Biological Evaluation and Testing Within a Risk Management Process, the FDA guidance document “Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" issued in September 2023, and ISO 14971:2019 Medical Devices - Application of Risk Management to Medical Devices. The Spring Implant is categorized as an implant device with long-term duration tissue contact, and the Delivery System is categorized as an external communicating device for a limited contact duration. Table 1 lists the biocompatibility testing completed on the Spring Implant and the Delivery System. | Test Name | Spring Implant | Delivery System | | --- | --- | --- | | Cytotoxicity (MEM Elution) | X | X | | ISO 10993-5 2009 | | | | Sensitization (Magnusson-Kligman) | X | X | | ISO 10993-10 2021 | | | | Irritation or Intracutaneous Reactivity | X | X | | ISO 10993-10 2021 | | | | Acute Systemic Toxicity | X | X | | ISO 10993-11 2017 | | | | Material Mediated Pyrogenicity | X | X | | USP-NF M98900_01_01 2021 <151> | | | | Subchronic Toxicity | X | n/a | | ISO 10993-11 2017 | | | | Genotoxicity | X | n/a | | ISO 10993-3 2014 | | | | Implantation | X | n/a | | ISO 10993-6 2016 | | | | Chronic Toxicity | Rationale based on TRA | n/a | | ISO 10993-11 2017 | | | | Carcinogenicity | Rationale based on TRA | n/a | | ISO 10993-3 2014 | | | Table 1. Biocompatibility Testing for the Zenflow Spring® Implant and Delivery System PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {5} Nickel elution was evaluated in accordance with the FDA guidance document, Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol, issued in July 2021. The amount detected did not exceed $35~\mu \mathrm{g / day}$ (0.5 $\mu \mathrm{g / kg / day}$ for a $70~\mathrm{kg}$ adult), the recommended tolerable intake (TI) limit cited in the guidance. The chemical characterization study was performed based on the requirements of ISO 10993-18:2005 and an updated toxicological risk assessment (TRA) was conducted in conformance with ISO 10993-17 2023. The results of biocompatibility testing demonstrated that all patient-contacting components of the Zenflow Spring® Implant and Delivery System are biocompatible. # Zenflow Spring Implant - Magnetic Resonance (MR) Compatibility The Spring Implant was subjected to a series of tests to characterize its behavior while encountering potential hazards in the MR environment, including RF-induced heating at 1.5T and 3T, magnetically induced force, torque, and image distortion (FTID). Analyses and testing demonstrated that the Spring Implant conforms with the FDA guidance document, Testing and Labeling Medical Devices for Safety in the Magnetic Resonance (MR) Environment issued on October 10, 2023 as well as standards ASTM F2182-19, ASTM F2119-24, ASTM F2052-21. # Zenflow Spring Implant Mechanical Testing As described in Table 2, design verification testing was conducted to demonstrate that the system met all design inputs. The results of design verification testing demonstrated that all design input requirements for the Zenflow Spring® Implant and Delivery System were met. | Test | Method | Acceptance Criteria | Results | | --- | --- | --- | --- | | Implant Mechanical Testing | | | | | Spring Implant mechanical testing – fatigue | ISO 25539-2 (2017), ISO 25539-2 (2012) and ASTM F2477 (2013) | The implant must withstand radial fatigue associated with a 30-year lifecycle, or 1 million fatigue cycles and 1560 ejaculation cycles. Assessed via visual inspection of ring, spine, or tail fractures, lumen collapse, and wall apposition throughout test. | Pass | | Spring Implant Corrosion | ASTM F2129-17b (2017) and ASTM F2129-19a (2019) | The breakdown potential (Eb) must be larger than or equal to 300 mV. (Eb ≥ 300 mV). | Pass | | Spring Delivery System Design Verification Testing | | | | | Unlock Knob Actuation Force | Applicant internal method | Force required to unlock delivery system prior to deployment shall not exceed 9.3 lbf. | Pass | PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {6} PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 7 of 47 | Test | Method | Acceptance Criteria | Results | | --- | --- | --- | --- | | Instant Release Actuation Force [Unlock Knob Connection] | Applicant internal method | The Instant Release Mechanism shall require no more than 5.91lbf to actuate. | Pass | | Unlock Knob connection to the Record Player housing during actuation of the Unlock Knob | Applicant internal method | The Unlock Knob shall remain connected to the Record Player Housing during actuation of the Unlock Knob. | Pass | | Push Wire to Reel Tensile Strength | Applicant internal method | The Push Wire to Reel connection withstands a tensile load of at least 4.45lbf without failure. | Pass | | Balloon to Tether Shaft Bond | Applicant internal method | The distal end of the Tether Shaft resists a load of at least 5.10 lbf without failure. | Pass | | Trigger Deployment Force | Applicant internal method | Force applied to the trigger during deployment of the Implant shall not exceed 15.0 lbf. | Pass | | Delivery System Insertion | Simulated procedure | The Delivery System must pass through the Scope working channel | Pass | | Implant Deployment/Unsheathing | Simulated procedure | System must enable 3 deployments of the implant in an untangled, axial configuration before release. | Pass | | Average Trigger Retraction Force | Applicant internal method | Average force applied to the trigger during any full deployment or retraction of the Implant shall not exceed 4.67 lbf. | Pass | | Balloon Seal | Simulated procedure | When inflated to 40cc of air, the balloon remains inflated throughout the procedure. | Pass | | Balloon Deflation | Simulated procedure | When inflated with 40cc of air, the balloon must deflate in less than 15 seconds when pulling full vacuum on a 60cc syringe. | Pass | {7} PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 8 of 47 | Test | Method | Acceptance Criteria | Results | | --- | --- | --- | --- | | Balloon Diameter | Simulated procedure | When inflated with 40cc, the balloon must measure at least 3 cm in diameter. | Pass | | Balloon Burst Volume | Simulated procedure | The balloon must be able to withstand inflation with 44cc of air (equal to 1.1x an inflation volume of 40cc). | Pass | | Tether Hold | Simulated procedure | The Tether must retain the proximal Implant tail until it is manually released by the user. | Pass | | Implant Release | Simulated procedure | The system must release the Implant when manually actuated by the user, without significantly affecting Implant position. | Pass | | Delivery System / Scope Rotation Detent | Simulated procedure | The Scope groove with the Delivery System plunger must ensure that the scope handle does not passively (inadvertently) rotate during implant delivery. In addition, the scope should be able to be rotatable (actively) from the delivery system if or when desired by the user. | Pass | | Inflation Tube to Inflation Manifold Tensile Strength | EN1618 (1997). | The Inflation Tube to Inflation Manifold joint resists a load of at least 9.83 lbf without failure. | Pass | | Tether Balloon Subassembly to Inflation Tube Tensile Strength | EN1618(1997) | The distal end of the Tether Shaft resists a load of at least 9.83 lbf without failure. | Pass | | Actuation Sheath Subassembly Tensile Strength | EN1618(1997) | The Square Tether Cover to Actuation Sheath weld resists a load of at least 4.42 lbf without failure. | Pass | | Actuation Sheath to Tether Collar Tensile Strength | EN1618 (1997) | The Actuation Sheath to Tether Collar joint resists a tensile load of at least 4.42 lbf without fail. | Pass | {8} | Test | Method | Acceptance Criteria | Results | | --- | --- | --- | --- | | Tygon Tube to Inflation Manifold Tensile Strength | EN1618 (1997) | The Inflation Manifold to Tygon Tube bond joint resists a tensile load of at least 2.88 lbf without failure. | Pass | | Square Tether Body to Inflation Tube Weld Tensile Strength | EN1618 (1997) | The Square Tether Body to Inflation Tube weld resists a load of at least 2.84 lbf without failure. | Pass | | Implant and Pocket Coupling | EN1618 (1997) | Implant and pocket coupling must be able to withstand a tensile load of at least 4.45 lbf without failure. | Pass | | Inner Shaft Subassembly Tensile Strength | EN1618 (1997) | The Inner Shaft (from the tip of the shaft to the square tube) must withstand a tensile force of at least 4.45 lbf. | Pass | | Lock Force | Applicant internal method | In the locked condition, the delivery device drivetrain should withstand a grip force of at least 44.6 lbf applied to the trigger of the device without moving past the lock position. | Pass | | Pocket Body to Push Wire Tensile Test | Applicant internal method | The Pocket Body to Pocket Wire connection withstands a tensile load of at least 4.45 lbf. | Pass | | Inner Shaft Nut Subassembly Tensile Test | Applicant internal method | The Inner Shaft Nut Subassembly (which includes the bond to the Square Tube) must withstand a tensile force of at least 4.45 lbf. | Pass | | Simulated Use Testing | | | | | Design Validation | Simulated use | Performance rating ≥ 2 (minimally suitable for clinical use) for any requirement. | Pass | Table 2. Bench testing conducted to support the performance of the Zenflow Spring Implant and Delivery System # Sterilization The Zenflow Spring® Implant and Delivery System is provided sterile and intended for single use. Sterilization information according to the FDA guidance document, PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {9} Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile (2024) is provided in Table 3. | Sterilization Method | Ethylene Oxide | | --- | --- | | Sterilization Site | Steris Applied Sterilization Technologies 43425 Business Park Drive Temecula, California 92590 | | Sterilization Validation Standards | ISO 11135:2014, Sterilization of health-care products - Ethylene oxide - Requirements for the development, validation and routine control of a sterilization process for medical devices. ISO 10993-7:2008, Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals. ISO 11138-1:2017, Sterilization of Healthcare Products - Biological Indicators - Part I: General Requirements. ISO 11138-2:2017, Sterilization of Healthcare Products - Biological Indicators - Part 2: Biological Indicators for Ethylene Oxide Sterilization Processes. ISO 11737-1:2018, Sterilization of medical devices - Microbiological methods - Part I: Determination of population of microorganisms on products. ISO 11737-2:2019, Sterilization of medical devices - Microbiological methods - Part 2: Tests of sterility in the definition. validation and maintenance of a sterilization process. ISO 11139:2018,Sterilization of health care products - Vocabulary - Terms used in sterilization and related equipment and process standards. AAMI TIRI4:2016, Contract sterilization using ethylene oxide. AAMI TIR15:2016/(R)2024, Physical aspects of ethylene oxide sterilization. AAMI TIRI6:2023, Microbiological aspects of ethylene oxide sterilization. AAMI TIR28:2016/(R)2024, Product adoption and process equivalence for ethylene oxide sterilization. | | Sterility Assurance Level (SAL) | 10-6 | | Sterile Packaging | The device is packaged in a thermoformed tray, which is placed in a Tyvek/Mylar pouch. Packaging validation demonstrated that the sterile barrier is not compromised under simulated transit conditions. | | Bacterial Endotoxin | Pyrogen testing is performed on a lot-by-lot basis. | | Shelf-Life | Shelf-life testing, including testing the sterile barrier after preconditioning and transit simulation (visual inspection, bubble leak, and seal strength tests) and functional testing as described in Table 2, was performed with results supporting a 30-month shelf life. | Table 3. Sterilization Information for the Zenflow Spring® Implant and Delivery System ## B. Animal Studies Preclinical animal studies included three pilot studies and one additional study conducted over a 1.5-year period and including 13 dogs (2 beagles and 11 hounds) with duration of implantation ranging from 7 to 269 days. The purpose of animal studies for the Zenflow Spring System was to demonstrate the overall in vivo safety of the device for the PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {10} following acceptance criteria: ability to deploy the device in the urethra; absence of migration when sized and placed appropriately; absence of encrustation or other adverse biologic response; absence of excessive "ingrowth" of urethral tissue; overall systemic biologic tolerance; presence of device integration into the urethral mucosa; ability of a living subject to void when the Spring Implant is in place; and visibility of the Spring Implant under fluoroscopy. The results and conclusions, particularly of the final animal study, supported the safety and effectiveness of the Zenflow Spring Implant. Due to the limitations of the animal model, the Zenflow Delivery System was not used; and therefore, delivery accuracy was a noted limitation of the model. Proper sizing and placement were attained in the final four animals, and no migration was observed. Implants in place for greater than 240 days showed minimal to no mucosal hyperplasia, and gross necropsy was unremarkable. The long-term histopathological images did not raise concern for significant edema or permanent tissue trauma. ## X. SUMMARY OF PRIMARY CLINICAL STUDIES The applicant conducted one First-In-Man (FIM) and three pilot studies, treating a total of 85 patients in the pilot studies, prior to initiating the BREEZE pivotal study. These initial studies supported the conceptual design, initial safety and effectiveness of the Spring Implant, and its viability as a treatment method for men with LUTS due to BPH. The pilot studies were used as evidence to support the initiation of the BREEZE pivotal study. ## ZEST First-In-Man (FIM) Study This FIH study evaluated the Zenflow Spring® Implant and Delivery System for treating LUTS due to BPH in men up to 50 years of age. The study was conducted at four sites with 13 participants enrolled and was extended from 12 months to three years of follow-up. ## Deployment Success: - 85% successful deployment rate (11 of 13 subjects received implants under fluoroscopic guidance). - 69% device success rate (defined as proper placement without serious/unanticipated adverse events for study duration). ## Long-term Outcomes: - 7 of 11 originally implanted subjects retained their implants at 3-year follow-up. - 4 subjects required implant removal due to various complications, including migration, inadequate symptom relief, and possible displacement during non-urological surgery. All explanted patients were successfully treated with alternative BPH surgeries (TURP, laser) without complications. Three serious adverse events (SAEs) occurred within the first year, including device migration requiring removal/replacement, infection with hematuria and retention, and urinary retention requiring suprapubic catheter and device PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {11} removal. All SAEs were transient and resolved quickly. No unanticipated device-related serious adverse events were reported. The primary effectiveness endpoint was met, with greater than or equal to 3-point IPSS improvement maintained at all follow-up visits. The FIH study identified key areas for improvement in future trials, particularly the need for enhanced Zenflow Spring Implant placement under direct visualization and refined patient selection criteria. ## ZEST 1 Pilot Study The ZEST 1 Pilot Study was a multi-center, prospective, single-arm clinical trial evaluating the Zenflow Spring® Implant and Delivery System for treating symptomatic LUTS associated with BPH conducted at four sites (Mexico-3, Australia-1). It involved men 45 years and older with symptomatic LUTS/BPH, prostate volume 25-80g, prostatic urethral length 25-45 mm, and baseline IPSS score ≥13. Thirty seven subjects consented, with 8 Roll-In subjects, and 22 Intent-to-Treat (ITT) subjects. Follow-up was originally planned for 24 months, extended to 60 months with assessments at 2 weeks, 1, 3, 6, 12, 24, 36, 48, and 60 months. - There was a 95.5% success rate (21/22 ITT subjects) for procedural success. - Improvements in IPSS Total Score at all timepoints through 36 months. - Improvements in IPSS-QoL scores maintained through 36 months. - Peak flow rate (Qmax) improved from 9.9 mL/s at baseline to 14.8 mL/s at 48 months, with improvements through 24 months. - 66.7% of subjects (20/30) reported at least one adverse event, with 42 total events recorded. - 16 device-related AEs in 8 subjects (26.7%), with urinary retention being the most common (n=11). - 8 SAEs in 4 subjects, with 3 related to device/procedure (1 procedure-related acute urinary retention, 2 device-related testicular abscesses in same subject). - No deterioration in erectile or ejaculatory function as measured by Sexual Health Inventory for Men (SHIM) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD) questionnaires. - 7 removals occurred (primarily due to patient choice/lack of effectiveness), all performed without adverse events The results informed design modifications for the subsequent ZEST 2 study to enhance visualization, delivery precision, and overall usability. ## ZEST 2 Pilot Study The ZEST 2 Pilot Study was a multi-center, prospective, single-arm safety, performance and effectiveness trial conducted across 7 sites in New Zealand and Australia, evaluating the Zenflow Spring® Implant and Delivery System for treating LUTS secondary to BPH with ongoing long-term follow-up through 5 years in 47 men aged 45 years and older with symptomatic LUTS associated with BPH who had failed, were intolerant to, or chose not to take medication. - There was a 97.9% (46 of 47) procedural success rate. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {12} - IPSS Total Score showed improvements at all timepoints through 36 months, above the validated minimum clinically important difference. - IPSS-QoL scores showed improvements through 60 months of follow-up. - Peak flow rates (Qmax) improved from 9.0 mL/s at baseline to 21.3 mL/s at 60 months. - No device-related deaths or unanticipated adverse device effects. - One procedure-related SAE (acute urinary retention, resolved). - No deterioration in erectile or ejaculatory function. - 17 device removals performed without adverse events. The results supported progression to pivotal IDE studies for regulatory approval. ## ZEST 3 Pilot Study The ZEST 3 Pilot Study was a multi-center, prospective, single-arm safety, performance, and effectiveness trial clinical trial evaluating the Zenflow Spring® Implant and Delivery System for treating LUTS secondary to BPH at 3 investigational sites in Canada in men ≥45 years with symptomatic LUTS associated with BPH. Fifty-eight subjects were consented, with 9 in Intent-to-Treat (ITT) subjects and 8 in Per Protocol (PP) subjects. Those treated were followed 2 weeks through 5 years. Safety endpoints including catheterization rates and serious adverse events; performance endpoints including procedural success and IPSS improvement. - There was a procedural success rate of 91% (10 of 11 subjects). - Improvement in IPSS Total Scores at all timepoints through 36 months. - Improvements in QoL scores and urinary flow metrics. - No device or procedure-related deaths or serious adverse events. - No extended post-operative catheterization incidents. - Three SAEs reported in 2 subjects, all unrelated to device/procedure. - Sexual health maintained throughout follow-up. - One device removal due to lack of effectiveness (no adverse events). ## BREEZE Pivotal Clinical Trial The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the Zenflow Spring® Implant and Delivery System in the treatment of symptoms due to urinary outflow obstruction secondary to BPH in the US and Canada under IDE G210096. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ## A. Study Design Patients were treated between September 2021 and March 2023. The database for this PMA reflected data collected through October 2024 and included 231 patients. There were 28 investigational sites. The study was a prospective, multi-center, multinational, 2:1 randomized treatment:sham), single-blinded, controlled clinical study. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {13} The trial execution and safety results were reviewed by both a Clinical Events Committee (CEC) and Data Safety Monitoring Board (DSMB). The control group included patients randomized to the sham arm following cystoscopic visualization. A catheter was inserted into the urethra of the sham arm patients, a balloon was deployed and inflated and tugged slightly to simulate a procedure, and no implant was deployed. ## 1. Clinical Inclusion and Exclusion Criteria Enrollment in the BREEZE study was limited to patients who met the following inclusion criteria: 1. Subject is able and willing to comply with all the assessments of the study 2. Subject or subject’s legal representative has been informed of the nature of the study, agrees to participate and has signed the informed consent form, 3. ≥ 45 years of age, 4. Baseline IPSS score ≥ 13; ≥ 1 in the IPSS voiding to storage sub-score ratio (IPSS-V/S) Sub Score ratio is (Q1+Q3+Q5+Q6)/(Q2+Q4+Q7) 5. Prostate volume 25 - 80 cc by transrectal ultrasound (TRUS) 6. Prostatic urethral length between 25 and 45 mm, as measured by cystoscopic pull-back and evaluation from the bladder neck to the verumontanum using the Spring Scope, 7. Failed, intolerant, or subject choice to not take a medication regimen for the treatment of LUTS. Patients were not permitted to enroll in the BREEZE study if they met any of the following exclusion criteria: 1. Subjects who met any of the following exclusion criteria were not eligible for the study: Obstructive intravesical median prostatic lobe as determined by ultrasound (i.e., more than 10 mm intravesical prostatic protrusion on sagittal mid-prostate plane via ultrasound), 2. High bladder neck with the absence of lateral lobe encroachment indicating a high likelihood of primary bladder neck obstruction as determined by the Investigator, 3. Urethral stricture, meatal stenosis, or bladder neck stricture - either current or recurrent, 4. Anatomical anomalies that will not accommodate the Implant, as determined by cystoscopy (e.g., prostatic urethral length to height geometry), 5. Requires indwelling catheter or intermittent catheterization to void, 6. Baseline prostate serum antigen (PSA) > 10 ng/mL or confirmed or suspected prostate cancer (Subjects with a PSA level above 2.5 ng/mL, or age specific, or local reference ranges should have prostate cancer excluded to the Investigator’s satisfaction), PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {14} 7. One of the following baseline test results, taken from a single uroflowmetry reading: a. Urinary volume void < 125 mL (pre-bladder urinary volume of ≥ 150 mL required), b. Peak urinary flow rate (Qmax) of < 5 mL/second and > 15 mL/second, c. Post-void residual volume (PVR) > 250 mL 8. History of other diseases causing voiding dysfunction including urinary retention (e.g., uncontrolled diabetes, diagnosis of neurogenic bladder, Parkinson's disease, multiple sclerosis, etc.), 9. Subjects with overactive bladder in the absence of benign prostatic obstruction, 10. Acute urinary tract infection (UTI) or finding of asymptomatic bacteriuria (Note: subject can be enrolled if the UTI is treated and followed with a negative urine test result), or subjects with history of recurrent UTIs (defined as > 3 UTIs in the past 12 months), 11. Concomitant bladder stones, 12. Previous pelvic irradiation or radical pelvic surgery, 13. Previous prostate surgery, including: enucleation, resection, vaporization, thermotherapy, ablation, stenting or prostatic urethral lift, 14. Chronic prostatitis, recurrent prostatitis, chronic pelvic pain syndrome (CPPS), or painful bladder syndrome within the past 12 months, 15. Known allergy to nickel, 16. Life expectancy less than 60 months, 17. Inability to stop taking anticoagulants and/or antiplatelets for at least 3 days prior to the procedure or coumadin for at least 5 days prior to the procedure (Note: low dose aspirin therapy (81 mg) is permitted), 18. Use of Type II 5-alpha reductase inhibitor such as finasteride (Proscar, Propecia) within 3 months of baseline assessment, 19. Use of Type I 5-alpha reductase inhibitor such as dutasteride (Avodart) within 6 months of baseline assessment, 20. Taking one of the following within 2 weeks of baseline evaluation: a. alpha-blockers, b. tricyclic anti-depressants (e.g., imipramine), c. anticholinergics, d. cholinergic gonadotropin releasing hormonal analogues, e. Phosphodiesterase-5 Enzyme Inhibitors (Tadalafil) in doses for BPH, f. Beta-3 adrenergic receptor agonist (Mirabegron), 21. Taking androgens, unless eugonadal state for at least 3 months or greater as documented by the Investigator, 22. Taking one of the following within 24 hours of pre-treatment (baseline) evaluation: a. phenylephrine, or, b. pseudoephedrine, 23. Future fertility concerns, or, 24. In the Investigator's opinion, the subject has a physical, psychological, or medical impairment that might prevent study completion or would confound study results (including subject questionnaires). PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 15 of 47 {15} PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 16 of 47 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at 2 weeks, 1 month, 3 months, 6 months, and 12 months. Preoperatively, the following assessments were performed: - Uroflowmetry - PVR - IPSS - QoL Questionnaire - MSHQ + EjD Questionnaire - SHIM Questionnaire - concomitant medications Postoperatively, the objective parameters measured during the study included the following: - Uroflowmetry - PVR - IPSS - QoL Questionnaire - MSHQ + EjD Questionnaire - SHIM Questionnaire - concomitant medications Adverse events and complications were recorded at all visits. The key timepoints are shown below in the tables summarizing safety and effectiveness. 3. Clinical Endpoints With regards to safety, the co-primary safety outcomes were the rate of extended post-operative urinary catheterization (> 7 days from treatment) for inability to void among subjects treated with the Zenflow Spring System and the rate of device or procedure related serious adverse events, at discharge through the 12-month follow-up visit. The secondary safety endpoints were: - Rate of device or procedure related adverse events at all time points, - Comparison of pain at discharge to 2-week, 1- and, 3-month follow-up visits per Visual Analogue Scale (VAS) questionnaire, - Change in sexual health characterized by change in SHIM and MSHQ-EjD at 3-, 6-, 12-, and 24- month post treatment, - Assessment of adverse events outcomes related to a Spring Implant removal procedure, and - Proportion of subjects with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability evidenced through 3-month follow-up visit. {16} With regards to effectiveness, the co-primary efficacy outcomes were: - the percent of subjects who experience at least a 30 percent improvement in IPSS from their baseline pre-treatment score at the 3-month follow-up visit and - the mean percent change in IPSS for the Spring Treatment Arm being at least 30% improved over baseline at 12 months. The secondary effectiveness endpoints were: - the mean change from baseline in IPSS at all timepoints through 12 Months, - the percent of subjects in the Spring Implant arm who experience at least a 30% improvement in IPSS from their baseline pre-treatment score at 6-, and 12-month follow-up visits, - the mean percent change in the IPSS Total Score in the treatment arm compared to baseline at all timepoints other than the primary endpoints, - the mean change from baseline in uroflowmetry measures of peak flow rate (Qmax) at follow-up visits, - the post-procedure incidence of secondary reintervention using an alternate surgical procedure for LUTS therapy, and - the post-procedure incidence of secondary reintervention using standard pharmacological agents for LUTS therapy. With regard to success/failure criteria, the study is considered a success when the following conditions are met: - The percentage of subjects who experience at least a 30 percent improvement in IPSS from their baseline pre-treatment score at the 3-month follow-up visit is greater in the treatment arm than in the sham arm. - At 12 months, the mean percent improvement in IPSS for the Spring Implant group is at least 30%. Since a decrease in IPSS is consistent with improvement, this equates to showing that the mean percent change from baseline in IPSS for the Spring Implant group is less than -30%. - The device demonstrates an acceptable safety profile. ## B. Accountability of PMA Cohort At the time of database lock, of 231 patients enrolled in the PMA study and who received an index procedure, 163 subjects received an implant (roll-in cohort, n=26, treatment arm, n=137). There were 68 subjects in the control arm who were not implanted. One hundred and forty-nine implanted subjects (149/163, 91.4%) were available for analysis at the 12-month post-operative visit. Patients were considered enrolled after signing the informed consent form. Subject disposition flowcharts are provided in Figures 3 and 4. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {17} ![img-2.jpeg](img-2.jpeg) Figure 3. Subject Disposition Flowchart (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {18} ![img-3.jpeg](img-3.jpeg) Figure 4. Subject Disposition Flowchart (Crossover Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {19} PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 20 of 47 # Analysis Population ## Intent-to-Treat (ITT) and Safety The ITT/Safety cohort includes all subjects who were randomized and started the treatment procedure (insertion of the Zenflow Delivery System into the Spring Scope) or sham procedure (catheter insertion and balloon inflation). Where there is an attempt to treat, the subject was considered enrolled in the ITT/Safety cohort, regardless of the procedural outcome. The ITT/Safety cohort was used to analyze all primary and secondary efficacy endpoints and all safety endpoints. For efficacy endpoints, outcomes were evaluated according to the subjects' randomized treatment assignment. For safety endpoints, outcomes were evaluated according to the actual treatment subjects received. ## Crossover The crossover cohort includes the sham arm subjects who elected after the 3-month follow-up visit to undergo the Spring Implant procedure. Data from the crossover cohort were descriptively summarized, separately from the subjects who are randomized to the Spring Implant arm. They were not included with randomized subjects in the endpoint evaluations of the study. ## C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a BPH study performed in the US. Demographic and baseline characteristics responses were summarized with descriptive statistics by treatment group and for all subjects for the ITT population. Demographics of study subjects and study subject baseline IPSS are summarized in Table 4 and Table 5. Treatment and control arms were similar at baseline. {20} | | Spring System (N=137) | Sham Device (N=68) | | --- | --- | --- | | Age (years) | | | | n | 137 | 68 | | Mean (SD) | 66.5 (8.17) | 66.9 (7.17) | | Median | 67.0 | 67.0 | | Min, Max | 45, 85 | 52, 83 | | Ethnicity - n/N (%) | | | | Hispanic or Latino | 14/137 (10.2%) | 6/68 (8.8%) | | Not Hispanic or Latino | 122/137 (89.1%) | 62/68 (91.2%) | | Not Reported | 1/137 (0.7%) | 0/68 (0.0%) | | Race - n/N (%) | | | | White | 126/137 (92.0%) | 63/68 (92.6%) | | Asian | 2/137 (1.5%) | 4/68 (5.9%) | | Middle Eastern | 1/137 (0.7%) | 1/68 (1.5%) | | Black | 4/137 (2.9%) | 0/68 (0.0%) | | Other | 4/137 (2.9%) | 0/68 (0.0%) | | Height (cm) | | | | n | 137 | 68 | | Mean (SD) | 176.3 (8.42) | 175.7 (7.52) | | Median | 175.3 | 177.7 | | Min, Max | 155, 201 | 155, 191 | | Weight (kg) | | | | n | 135 | 68 | | Mean (SD) | 91.0 (17.86) | 91.4 (16.64) | | Median | 89.8 | 88.2 | | Min, Max | 58, 184 | 67, 154 | | BMI (kg/m2) | | | | n | 135 | 68 | | Mean (SD) | 29.35 (5.945) | 29.67 (5.428) | | Median | 28.12 | 28.25 | | Min, Max | 20.5, 62.3 | 21.1, 45.8 | | History of smoking - n/N (%) | | | | Non-smoker | 78/137 (56.9%) | 39/68 (57.4%) | | Current/recently quit | 14/137 (10.2%) | 2/68 (2.9%) | | Former smoker | 45/137 (32.8%) | 27/68 (39.7%) | Table 4. Summary of Demographic and Baseline Characteristics by Treatment Arm (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {21} | | Spring System (N=137) | Sham Device (N=68) | | --- | --- | --- | | IPSS | | | | Total Score | | | | n | 137 | 68 | | Mean (SD) | 23.7 (5.35) | 22.7 (4.56) | | Median | 24.0 | 22.5 | | Min, Max | 13, 34 | 14, 31 | | 95% CI of Mean | 22.8, 24.6 | 21.6, 23.8 | | QoL Score | | | | n | 137 | 68 | | Mean (SD) | 4.5 (1.12) | 4.6 (1.01) | | Median | 5.0 | 5.0 | | Min, Max | 2, 6 | 2, 6 | | 95% CI of Mean | 4.3, 4.7 | 4.3, 4.8 | Table 5. Summary of Baseline IPSS by Treatment Arm (ITT Population) ## D. Safety and Effectiveness Results ### 1. Safety Results The analysis of safety was based on the ITT/safety cohort of 205 patients (Spring Implant, n=137; sham, n=68) available for the 12-month evaluation. The key safety outcomes for this study are presented below in Tables 6 to 9. Adverse effects are reported in Tables 10 to 13. #### Primary Safety Endpoints There were no reports of any extended post-operative urinary catheterization and there were no device or procedure related serious adverse events reported in the Spring Implant arm subjects through 12 months of follow-up. #### Secondary Safety Endpoints The first secondary safety endpoint was the rate of device or procedure related adverse events at all time points (Table 6). Because the sham arm subjects were only followed for 3 months before crossover, events are reported for procedure through the 3-month timepoint only for those subjects. Within the 3-month follow-up period, there were 4 device related AEs reported for the Spring Implant arm subjects (2.9%) and none for the sham arm. After 3 months, two additional subjects had device-related AEs reported in the Spring Implant arm through 12 months of follow-up. The cumulative by subject rate of all device-related adverse events reported from procedure through 12 months of follow-up was 4.4% (6/137). The rate of procedure-related events in the 3-month period was 9.5% (n=13) in the Spring Implant arm and 4.4% (n=3) in the sham arm. Two additional procedure-related events were reported in the Spring Implant arm subjects between 3 and 12 months of follow-up. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {22} | | Spring System (N=137) | Sham Device (N=68) | Difference (Treatment - Control, 95% CI) | | --- | --- | --- | --- | | Rate of Device Related Adverse Events - n/N (%) | | | | | Within 3 Months | 4/137 (2.9%) (1.1%, 7.3%) | 0/68 (0.0%) (0.0%, 5.3%) | 2.9% (-2.7%, 7.3%) | | Within 12 Months* | 6/137 (4.4%) (2.0%, 9.2%) | | | | Rate of Procedure Related Adverse Events - n/N (%) | | | | | Within 3 Months | 13/137 (9.5%) (5.6%, 15.6%) | 3/68 (4.4%) (1.5%, 12.2%) | 5.1% (-3.6%, 11.8%) | | Within 12 Months | 15/137 (10.9%) (6.7%, 17.3%) | | | *Cumulative – includes all events reported from procedure through 12 months The 95% CIs are derived using the score-based method (Wilson approach for individual proportions and Newcombe approach for proportion difference). Table 6. Secondary Safety Endpoint: Rate of Device or Procedure Related Adverse Events (ITT Population) The second secondary safety endpoint was the comparison of pain at discharge to 2- week, 1- and, 3-month follow-up visits per a Visual Analogue Scale (VAS) questionnaire (Table 7). The mean improvement in VAS from discharge was summarized by treatment group and descriptive statistics for the ITT population. The analysis of the mean change from discharge to 2-weeks, 1 and 3-months in VAS in the Spring Implant arm found that the mean scores decreased with time, such that by one month after the procedure VAS scores were comparable to those observed in the sham control arm. At discharge, the mean VAS score in the Spring Implant subjects was 2.4 (on a scale of 0-10). PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {23} | | Baseline | Discharge | 2 Weeks | 1 Month | 3 Months | | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=137) | | | | | | | VAS (cm) | | | | | | | n | 136 | 137 | 134 | 135 | 133 | | Mean (SD) | 0.6 (1.11) | 2.4 (2.39) | 1.1 (1.96) | 0.7 (1.38) | 0.4 (0.75) | | Median | 0.0 | 1.6 | 0.1 | 0.1 | 0.0 | | Min, Max | 0, 5 | 0, 9 | 0, 9 | 0, 7 | 0, 5 | | 95% CI of | 0.4, 0.8 | 2.0, 2.8 | 0.8, 1.4 | 0.5, 1.0 | 0.3, 0.5 | | Mean | | | | | | | VAS Change from Discharge | | | | | | | n | | | 134 | 135 | 133 | | Mean (SD) | | | -1.3 (2.60) | -1.6 (2.38) | -2.0 (2.36) | | Median | | | -0.7 | -1.0 | -1.4 | | Min, Max | | | -8, 8 | -8, 5 | -9, 2 | | 95% CI of | | | -1.7, -0.8 | -2.0, -1.2 | -2.4, -1.6 | | Mean | | | | | | | Sham Device (N=68) | | | | | | | VAS (cm) | | | | | | | n | 68 | 68 | 66 | 66 | 68 | | Mean (SD) | 0.8 (1.64) | 0.8 (1.38) | 0.4 (0.94) | 0.4 (1.01) | 0.5 (1.25) | | Median | 0.0 | 0.2 | 0.0 | 0.0 | 0.0 | | Min, Max | 0, 8 | 0, 7 | 0, 4 | 0, 4 | 0, 8 | | 95% CI of | 0.4, 1.2 | 0.5, 1.2 | 0.1, 0.6 | 0.2, 0.7 | 0.2, 0.8 | | Mean | | | | | | | VAS Change from Discharge | | | | | | | n | | | 66 | 66 | 68 | | Mean (SD) | | | -0.5 (1.61) | -0.4 (1.32) | -0.4 (1.55) | | Median | | | -0.1 | 0.0 | 0.0 | | Min, Max | | | -7, 4 | -7, 4 | -7, 7 | | 95% CI of | | | -0.9, -0.1 | -0.8, -0.1 | -0.8, -0.0 | | Mean | | | | | | The $95\%$ CIs are constructed based on t-distribution. Reported data only with no imputation for missing data. # Table 7. Secondary Safety Analysis: Summary of Visual Analogue Scale (VAS) (ITT Population) The third secondary safety endpoint was the change in sexual health characterized by change in Sexual Health Inventory for Men (SHIM) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD) at 3, 6, and 12 months post treatment (Tables 8 and 9). The results from the Sexual Health Inventory in Men (SHIM) reported during the study indicated that the subjects experienced no deterioration in erectile function following treatment with the Zenflow Spring System through 12 months of follow-up. The results from the MSHQ-EjD PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {24} questionnaire found that subjects experienced no deterioration in ejaculatory function following treatment with the Zenflow Spring System through 12 months of follow-up. | | Baseline | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | | Zenflow Spring System (N=137) | | | | | | Not Sexually Active - n/N (%) | 28/137 (20.4%) | 19/134 (14.2%) | 26/129 (20.2%) | 33/124 (26.6%) | | SHIM Total Score | | | | | | n | 109 | 115 | 103 | 91 | | Mean (SD) | 16.2 (6.69) | 16.5 (7.21) | 17.4 (6.51) | 17.5 (6.45) | | Median | 17.0 | 18.0 | 19.0 | 19.0 | | Min, Max | 1, 25 | 1, 25 | 1, 25 | 1, 25 | | 95% CI of Mean | 14.9, 17.5 | 15.1, 17.8 | 16.1, 18.7 | 16.1, 18.8 | | SHIM Change from Baseline | | | | | | n | | 101 | 94 | 85 | | Mean (SD) | | 0.5 (5.47) | 1.1 (4.47) | 1.1 (4.07) | | Median | | 1.0 | 1.0 | 1.0 | | Min, Max | | -20, 19 | -13, 14 | -13, 14 | | 95% CI of Mean | | -0.5, 1.6 | 0.2, 2.0 | 0.2, 1.9 | | Sham Device (N=68) | | | | | | Not Sexually Active - n/N (%) | 13/68 (19.1%) | 11/68 (16.2%) | | | | SHIM Total Score | | | | | | n | 55 | 57 | | | | Mean (SD) | 14.5 (6.18) | 14.3 (7.55) | | | | Median | 15.0 | 15.0 | | | | Min, Max | 2, 25 | 1, 25 | | | | 95% CI of Mean | 12.8, 16.1 | 12.3, 16.3 | | | | SHIM Change from Baseline | | | | | | n | | 51 | | | | Mean (SD) | | 0.7 (5.74) | | | | Median | | 0.0 | | | | Min, Max | | -11, 14 | | | | 95% CI of Mean | | -0.9, 2.4 | | | The 95% CIs are constructed based on t-distribution. Reported data only with no imputation for missing data. Table 8. Secondary Safety Analysis: Sexual Health Inventory for Men (SHIM) Score by Visit (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {25} | | Baseline | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | | Zenflow Spring System (N=137) | | | | | | Not Sexually Active - n/N (%) | 36/137 (26.3%) | 29/134 (21.6%) | 26/129 (20.2%) | 31/124 (25.0%) | | MSHQ-EjD Ejaculatory Function Score | | | | | | n | 101 | 105 | 103 | 93 | | Mean (SD) | 9.0 (2.72) | 10.7 (3.09) | 10.9 (2.87) | 10.2 (2.82) | | Median | 9.0 | 11.0 | 11.0 | 11.0 | | Min, Max | 3, 15 | 1, 15 | 1, 15 | 3, 15 | | 95% CI of Mean | 8.5, 9.6 | 10.1, 11.3 | 10.3, 11.5 | 9.6, 10.8 | | MSHQ-EjD Change from Baseline | | | | | | n | | 91 | 91 | 86 | | Mean (SD) | | 1.7 (3.24) | 2.1 (3.10) | 1.3 (2.87) | | Median | | 2.0 | 2.0 | 1.0 | | Min, Max | | -9, 8 | -6, 9 | -8, 7 | | 95% CI of Mean | | 1.1, 2.4 | 1.5, 2.8 | 0.7, 1.9 | | Sham Device (N=68) | | | | | | Not Sexually Active - n/N (%) | 20/68 (29.4%) | 20/68 (29.4%) | | | | MSHQ-EjD Ejaculatory Function Score | | | | | | n | 48 | 48 | | | | Mean (SD) | 8.5 (2.83) | 10.2 (3.13) | | | | Median | 9.0 | 11.0 | | | | Min, Max | 1, 13 | 4, 15 | | | | 95% CI of Mean | 7.7, 9.3 | 9.3, 11.1 | | | | MSHQ-EjD Change from Baseline | | | | | | n | | 43 | | | | Mean (SD) | | 1.5 (2.85) | | | | Median | | 1.0 | | | | Min, Max | | -4, 12 | | | | 95% CI of Mean | | 0.6, 2.4 | | | The 95% CIs are constructed based on t-distribution. Reported data only with no imputation for missing data. Table 9. Secondary Safety Analysis: MSHQ-EjD Ejaculatory Function Score by Visit (ITT Population) The fourth secondary safety endpoint was an assessment of adverse events outcomes related to a Spring Implant removal procedure. None of the subjects who PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {26} had an implant removed reported an AE associated with the implant removal procedure. Two subjects (1 ITT and 1 crossover) had a prophylactic catheter placed following the removal procedure at the Investigator's discretion. The fifth secondary safety endpoint was the proportion of subjects with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability evidenced through 3-month follow-up visit. There were no reported adverse events classified as Clavien-Dindo Grade IIIb or higher for any of the ITT population subjects from procedure through 12 months of follow-up. ## Adverse effects (AE) that occurred in the PMA clinical study: There were 152 reported AEs and, of these, 24 (15.8%) were reported as related to the Spring Implant or sham procedure (Table 10). Thirty (21.9%) of the Spring Implant subjects and 11 (16.2%) of the sham subjects reported adverse events. There were 8 device-related AEs (5.3%). The remaining 120 AEs (78.9%) were reported as having no relationship to the device or procedure. | | Zenflow Spring System (N=137) | | Sham Device (N=68) | | | --- | --- | --- | --- | --- | | | Events | Subjects n/N (%) | Events | Subjects n/N (%) | | Any treatment emergent adverse events | 51 | 30/137 (21.9%) | 15 | 11/68 (16.2%) | | Serious adverse events | 3 | 3/137 (2.2%) | 1 | 1/68 (1.5%) | | Severe adverse events | 2 | 2/137 (1.5%) | 1 | 1/68 (1.5%) | | Fatal adverse events | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | Not related adverse events | 30 | 19/137 (13.9%) | 10 | 9/68 (13.2%) | | Device- or procedure-related adverse events | 21 | 16/137 (11.7%) | 5 | 3/68 (4.4%) | | Device-related adverse events | 4 | 4/137 (2.9%) | 0 | 0/68 (0.0%) | | Procedure-related adverse events | 17 | 13/137 (9.5%) | 5 | 3/68 (4.4%) | | Adverse events with Clavien-Dindo Grade IIIb or higher | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Serious adverse events | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | Severe adverse events | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | Fatal adverse events | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | Table 10. Summary of Adverse Event Characteristics through 3 Months (ITT Population) During the first three months of follow-up, 66 events were reported in 41 subjects (Table 11). There were 21 device- or procedure-related adverse events in the Spring Implant group and 5 in the sham group. Of those in the Spring Implant group, 4 were noted as device-related and 15 were noted as procedure-related. Of those in the sham group, none were noted as device-related and 3 were noted as procedure-related. Four AEs were not adjudicated as device- or procedure-related but were instead adjudicated for severity. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {27} | System Organ Class Lowest Level Term | Relationship | Zenflow Spring System (N=137) | | Sham Device (N=68) | | | --- | --- | --- | --- | --- | --- | | | | Events | Subjects n/N (%) | Events | Subjects n/N (%) | | Subjects reporting any device- or procedure-related treatment emergent adverse events | | 21 | 16/137 (11.7%) | 5 | 3/68 (4.4%) | | Reproductive system and breast disorders | | 11 | 8/137 (5.8%) | 2 | 2/68 (2.9%) | | Painful ejaculation | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 6 | 6/137 (4.4%) | 0 | 0/68 (0.0%) | | | Device Related | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | Penile pain | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | | Device Related | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | Painful external genitals | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | | Device Related | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Perineal pain | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | | Device Related | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Retrograde ejaculation | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | | Device Related | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Perineal discomfort | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | | Device Related | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Renal and urinary disorders | | 7 | 7/137 (5.1%) | 1 | 1/68 (1.5%) | | Dysuria | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 5 | 5/137 (3.6%) | 1 | 1/68 (1.5%) | | | Device Related | 2 | 2/137 (1.5%) | 0 | 0/68 (0.0%) | | Musculoskeletal and connective tissue disorders | | 2 | 2/137 (1.5%) | 0 | 0/68 (0.0%) | | Back pain | Unrelated | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Procedure Related | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | | Device Related | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Groin pain | Mild | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | | Moderate | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Severe | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Gastrointestinal disorders | | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | Rectal pain | Mild | 1 | 1/137 (0.7%) | 0 | 0/68 (0.0%) | | | Moderate | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Severe | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | General disorders & administration site conditions | | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | Fever | Mild | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | | Moderate | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Severe | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | Infections and infestations | | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | | Urinary tract infection | Mild | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Moderate | 0 | 0/137 (0.0%) | 0 | 0/68 (0.0%) | | | Severe | 0 | 0/137 (0.0%) | 1 | 1/68 (1.5%) | Table 11. Procedure and Device Related Adverse Events Between Procedure and 3 Months (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {28} Between 3 and 12 months, a total of 52 events in the Spring Implant arm were reported in 34 subjects. Four of these events (in 2 subjects) were device related, and 2 events (in 2 subjects) were procedure related. The remaining 46 events were not related to the device or procedure. These are summarized in Table 12 and 13. | | Zenflow Spring System (N=137) | | | --- | --- | --- | | | Events | Subjects n/N (%) | | Any treatment emergent adverse events | 52 | 34/134 (25.4%) | | Serious adverse events | 8 | 8/134 (6.0%) | | Severe adverse events | 5 | 5/134 (3.7%) | | Fatal adverse events | 2 | 2/134 (1.5%) | | Not related adverse events | 46 | 32/134 (23.9%) | | Device- or procedure-related adverse events | 6 | 3/134 (2.2%) | | Device-related adverse events | 4 | 2/134 (1.5%) | | Procedure-related adverse events | 2 | 2/134 (1.5%) | | Adverse events with Clavien-Dindo Grade IIIb or higher | 0 | 0/134 (0.0%) | | Serious adverse events | 0 | 0/134 (0.0%) | | Severe adverse events | 0 | 0/134 (0.0%) | | Fatal adverse events | 0 | 0/134 (0.0%) | Table 12. Summary of Adverse Event Characteristics between 3 and 12 Months (ITT Population, Spring Implant Arm) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {29} | System Organ Class Lowest Level Term | Relationship | Zenflow Spring System (N=137) | | | --- | --- | --- | --- | | | | Events | Subjects n/N (%) | | Subjects reporting any device- or procedure-related treatment emergent adverse events | | 6 | 3/134 (2.2%) | | Renal and urinary disorders | | 3 | 3/134 (2.2%) | | Dysuria | Unrelated | 0 | 0/134 (0.0%) | | | Procedure Related | 0 | 0/134 (0.0%) | | | Device Related | 2 | 2/134 (1.5%) | | Urethral stricture | Unrelated | 0 | 0/134 (0.0%) | | | Procedure Related | 1 | 1/134 (0.7%) | | | Device Related | 0 | 0/134 (0.0%) | | Reproductive system and breast disorders | | 3 | 2/134 (1.5%) | | Painful ejaculation | Unrelated | 0 | 0/134 (0.0%) | | | Procedure Related | 1 | 1/134 (0.7%) | | | Device Related | 1 | 1/134 (0.7%) | | Perineal pain | Unrelated | 0 | 0/134 (0.0%) | | | Procedure Related | 0 | 0/134 (0.0%) | | | Device Related | 1 | 1/134 (0.7%) | Table 13. Procedure and Device Related Adverse Events Between 3 and 12 Months by (ITT Population, Spring Implant Arm) There were no device related patient deaths or other device related SAEs, and there were no unanticipated adverse device effects. A total of 16 SAEs were reported in 14 patients. One SAE that occurred in a sham subject was possibly related to the index procedure (urinary tract infection). The remaining 15 SAEs were not related to either the procedure or device. Three of those 15 SAEs were subject deaths, none of which were related to participation in the study. ## Zenflow Spring Implant Removals Eighteen patients (13.1%) had the device removed through 24 months. There were no reported removal procedure-related adverse events. The number of Spring Implants removed during the 1-year and 2-year follow-up periods and the reasons for removal are provided below: - 12 Months (n=3; 2.2%) - Painful urination/migration (n=1) - Patient choice (n=2) - 24 Months (n=15, 10.9%) - Medically indicated for non BPH reason (n=2) - Observed BPH disease progression (n=5) - Patient choice (n=8) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {30} PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) 31 of 47 ## 2. Effectiveness Results The analyses of effectiveness were based on the 205 evaluable patients at the 12-month time point. Key effectiveness outcomes are presented in Tables 14 to 26. ## Co-Primary Efficacy Endpoint #1 - ITT Population An analysis of the proportion of subjects achieving ≥30% improvement from baseline to 3 months in IPSS in the ITT population found that 51.8% (71/137) of subjects met this threshold in the Spring Implant arm and 39.7% (27/68) of subjects met this threshold in the sham arm (Table 14). The results of the hypothesis test found that the between-group difference did not achieve statistical significance in the ITT population (p=0.102). | | Zenflow Spring System (N=137) | Sham Device (N=68) | | --- | --- | --- | | Proportion of Subjects Achieving ≥30% Improvement from Baseline in IPSS Score at 3 Months - n/N (%) (95% CI) | 71/137 (51.8%) (43.5%, 60.0%) | 27/68 (39.7%) (28.9%, 51.6%) | | Difference (Treatment - Control, 95% CI) | 12.1% (-2.4%, 25.7%) | | | P-value | 0.102 | | The 95% CIs are derived using the score-based method (Wilson approach for individual proportions and Newcombe approach for proportion difference). The p-value is computed using Pearson's Chi-squared test. The Conditional Value Carried Forward approach is used for subjects missing their 3-Month IPSS (Spring arm BPH med use n=1, Early discontinuation not due to removal, n=3). ## Table 14. Co-Primary Efficacy Endpoint #1: Proportion of Subjects Achieving ≥30% Improvement from Baseline in IPSS Score at 3 Months (ITT Population) ## Co-Primary Efficacy Endpoint #2 - ITT Population The mean percent change in IPSS total score for the Spring Implant arm from baseline to 12 months was 32.1% (Table 15). Compared to a clinical success threshold of 30%, the Spring Implant arm did not achieve statistical significance for the ITT population (p=0.231). {31} | Zenflow Spring System (N=137) | | | --- | --- | | IPSS Score Percent Change from Baseline to 12 Months | | | n | 137 | | Mean (SD) | -32.1 (32.58) | | Median | -31.3 | | Min, Max | -100, 42 | | 95% CI of Mean | -37.6, -26.6 | | P-value | 0.231 | The 95% CI is constructed based on t-distribution. The p-value is computed using one-sided single-sample t-test, comparing against a performance goal of -30%. The Conditional Value Carried Forward approach is used for subjects missing their 12-Month IPSS. (Spring arm BPH med use n=6, Early discontinuation or missed visits not due to removal, n=8, Device removal n=3). Table 15. Co-Primary Efficacy Endpoint #2: Percent Change from Baseline in IPSS Score at 12 Months (ITT Population) The device met neither of the pre-specified co-primary effectiveness endpoints using the ITT analysis set. The ITT population includes 38 subjects (27 Spring Implant and 11 sham control subjects) who were erroneously enrolled in the ITT population and should have been excluded due to the presence of intravesical prostatic protrusion >10 mm and/or obstructive median prostatic lobe protrusion. These subjects were identified during a retrospective review of baseline imaging and confirmed via an independent retrospective review and analysis of all randomized subject screening imaging. As a result, the applicant completed an analysis of the effectiveness endpoints using the modified Intent-To-Treat/Intended Use (mITT/IU) population which excludes the subjects who did not meet these eligibility criteria. Table 16 and Table 17 provided the analysis of the co-primary effectiveness endpoints for the mITT/IU population. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {32} | | Zenflow Spring System (N=109) | Sham Device (N=57) | | --- | --- | --- | | Proportion of Subjects Achieving ≥30% Improvement from Baseline in IPSS Score at 3 Months - n/N (%) (95% CI) | 65/109 (59.6%) (50.2%, 68.4%) | 19/57 (33.3%) (22.5%, 46.3%) | | Difference (Treatment - Control, 95% CI) | 26.3% (10.3%, 40.2%) | | The 95% CIs are derived using the score-based method (Wilson approach for individual proportions and Newcombe approach for proportion difference). The Conditional Value Carried Forward approach is used for subjects missing their 3-Month IPSS. Table 16. Co-Primary Efficacy Endpoint #1: Proportion of Subjects Achieving ≥30% Improvement from Baseline in IPSS Score at 3 Months (mITT/IU Population) | | Zenflow Spring System (N=109) | | --- | --- | | IPSS Score Percent Change from Baseline to 12 Months | | | n | 109 | | Mean (SD) | -37.2 (32.68) | | Median | -39.1 | | Min, Max | -100, 39 | | 95% CI of Mean | -43.4, -31.0 | The 95% CI is constructed based on t-distribution. The Conditional Value Carried Forward approach is used for subjects missing their 12-Month IPSS. Table 17. Co-Primary Efficacy Endpoint #2: Percent Change from Baseline in IPSS Score at 12 Months (mITT/IU Population) ## Secondary Efficacy Endpoints The Spring Implant arm saw improvements in IPSS from baseline at all follow-up timepoints through 12 months (Table 18). The sham arm also saw improvements through 3 months. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {33} | | Baseline | 2 Weeks | 1 Month | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=137) | | | | | | | | IPSS Total Score | | | | | | | | n | 137 | 135 | 135 | 134 | 131 | 129 | | Mean (SD) | 23.7 (5.35) | 18.5 (7.19) | 15.5 (7.06) | 15.6 (7.99) | 14.8 (6.99) | 15.7 (7.78) | | Median | 24.0 | 20.0 | 14.0 | 15.0 | 15.0 | 16.0 | | Min, Max | 13, 34 | 1, 31 | 1, 33 | 2, 33 | 2, 34 | 0, 35 | | 95% CI of Mean | 22.8, 24.6 | 17.2, 19.7 | 14.3, 16.7 | 14.2, 16.9 | 13.6, 16.0 | 14.3, 17.0 | | IPSS Total Score Change from Baseline | | | | | | | | n | | 135 | 135 | 134 | 131 | 129 | | Mean (SD) | | -5.2 (7.94) | -8.1 (7.60) | -8.0 (8.03) | -8.8 (7.36) | -7.9 (7.77) | | Median | | -4.0 | -8.0 | -8.0 | -8.0 | -7.0 | | Min, Max | | -31, 16 | -30, 12 | -32, 9 | -29, 13 | -27, 8 | | 95% CI of Mean | | -6.5, -3.8 | -9.4, -6.8 | -9.4, -6.7 | -10.1, -7.6 | -9.2, -6.5 | | Sham Device (N=68) | | | | | | | | IPSS Total Score | | | | | | | | n | 68 | 66 | 66 | 68 | | | | Mean (SD) | 22.7 (4.56) | 17.1 (7.29) | 16.1 (7.84) | 16.9 (8.25) | | | | Median | 22.5 | 17.5 | 16.5 | 19.0 | | | | Min, Max | 14, 31 | 2, 30 | 1, 32 | 1, 31 | | | | 95% CI of Mean | 21.6, 23.8. | 15.3, 18.9. | 14.2, 18.0. | 14.9, 18.9 | | | | IPSS Total Score Change from Baseline | | | | | | | | n | | 66 | 66 | 68 | | | | Mean (SD) | | -5.5 (7.64) | -6.5 (8.02) | -5.8 (8.52) | | | | Median | | -4.0 | -5.0 | -5.0 | | | | Min, Max | | -24, 14 | -27, 17 | -29, 15 | | | | 95% CI of Mean | | -7.4, -3.6 | -8.5, -4.5 | -7.8, -3.7 | | | The $95\%$ CIs are constructed based on t-distribution. For subjects treated with BPH medications or those who undergo removal of the Spring device (not related to a device-related AE) from post-procedure through the 12-month study period, IPSS values recorded prior to the use of BPH medications or Spring device removal are carried forward to all subsequent visits through the 12-month visit. For subjects who undergo removal of the Spring device due to a device-related AE, the Baseline Value Carried Forward approach is applied. No imputation is performed for other missing IPSS scores. Table 18. Secondary Analysis: IPSS Total Score by Visit (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {34} Responder rates (>30% improvement) were consistent through 12 months for the Spring Implant group (Table 19). | | Zenflow Spring System (N=137) | | --- | --- | | 6 Months | | | n | 131 | | Responder Rate - n/N (%) | 78/131 (59.5%) | | 95% CI of Responder Rate | 51.0%, 67.6% | | 12 Months | | | n | 129 | | Responder Rate - n/N (%) | 69/129 (53.5%) | | 95% CI of Responder Rate | 44.9%, 61.9% | A responder is a subject whose IPSS score improves at least 30% from baseline. The 95% CIs are constructed based on t-distribution for continuous data, and score-based methods Wilson approach for categorical data. For subjects treated with BPH medications or those who undergo removal of the Spring device (not related to a device-related AE) at any time from post-procedure through the 12-month study period, IPSS values recorded prior to the use of BPH medications or Spring device removal are carried forward to all subsequent visits through the 12-month visit. For subjects who undergo removal of the Spring device due to a device-related AE, the Baseline Value Carried Forward approach is applied. No imputation is performed for other missing IPSS scores. Table 19. Secondary Analysis: Proportion of Subjects Achieving ≥ 30% Improvement from Baseline in IPSS Score at 6 and 12 Months (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {35} The mean percent change from baseline in IPSS score in the Spring Implant arm showed was higher than the sham arm at 3 months (Table 20). | | 2 Weeks | 1 Month | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=137) | | | | | | | IPSS Total Score Percent Change from Baseline | | | | | | | n | 135 | 135 | 134 | 131 | 129 | | Mean (SD) | -19.1 (35.20) | -32.8 (32.34) | -33.1 (33.38) | -36.4 (29.79) | -32.7 (32.70) | | Median | -16.7 | -36.8 | -34.8 | -36.8 | -31.8 | | Min, Max | -96, 123 | -94, 75 | -94, 60 | -91, 68 | -100, 42 | | 95% CI of Mean | -25.1, -13.1 | -38.3, -27.3 | -38.8, -27.4 | -41.5, -31.2 | -38.3, -27.0 | | Sham Device (N=68) | | | | | | | IPSS Total Score Percent Change from Baseline | | | | | | | n | 66 | 66 | 68 | | | | Mean (SD) | -22.6 (33.91) | -27.5 (35.31) | -23.8 (38.27) | | | | Median | -17.0 | -24.6 | -21.1 | | | | Min, Max | -92, 93 | -96, 113 | -96, 100 | | | | 95% CI of Mean | -30.9, -14.2 | -36.2, -18.9 | -33.0, -14.5 | | | | Difference in Mean | 3.5 | -5.2 | -9.3 | | | | (95% CI) | (-6.8, 13.8) | (-15.1, 4.7) | (-19.7, 1.0) | | | A responder is a subject whose IPSS score improves at least 30% from baseline. The 95% CIs are constructed based on t-distribution for continuous data, and score-based methods (Wilson approach for individual proportions and Newcombe approach for proportion difference) for categorical data. For subjects treated with BPH medications or undergo implant removal (not related to a device-related AE) post-procedure through 12-months, IPSS values prior to use of BPH medications or implant removal are carried forward to all visits through the 12-month visit. For subjects who undergo implant removal due to a device-related AE, the Baseline Value Carried Forward approach is applied. No imputation is performed for other missing IPSS scores. Table 20. Secondary Analysis: Percent Change from Baseline in IPSS Total Score by Visit (ITT Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {36} Peak flow rate (Qmax) improved from baseline through 12 months in the Spring Implant group (Table 21). | | Baseline | 2 Weeks | 1 Month | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=137) | | | | | | | | Qmax (mL/2s) | | | | | | | | n | 134 | 108 | 119 | 114 | 114 | 106 | | Mean (SD) | 9.43 (2.714) | 12.16 (3.961) | 12.78 (5.069) | 12.05 (4.953) | 11.72 (5.245) | 11.21 (4.570) | | Median | 9.20 | 12.00 | 11.50 | 11.00 | 10.95 | 10.00 | | Min, Max | 5.0, 15.0 | 5.0, 26.0 | 3.0, 30.0 | 4.0, 31.0 | 4.0, 33.0 | 4.0, 26.5 | | 95% CI of Mean | 8.97, 9.90 | 11.40, 12.91 | 11.86, 13.70 | 11.13, 12.97 | 10.75, 12.70 | 10.33, 12.09 | | Qmax Change from Baseline | | | | | | | | n | | 107 | 117 | 113 | 113 | 105 | | Mean (SD) | | 2.70 (3.868) | 3.55 (4.662) | 2.54 (5.185) | 2.27 (5.616) | 1.82 (4.659) | | Median | | 2.50 | 3.00 | 2.00 | 1.40 | 1.10 | | Min, Max | | -9.5, 12.0 | -6.4, 20.0 | -7.5, 21.6 | -7.5, 23.6 | -8.9, 16.0 | | 95% CI of Mean | | 1.96, 3.44 | 2.70, 4.41 | 1.57, 3.50 | 1.22, 3.32 | 0.92, 2.72 | | Qmax Percent Change from Baseline | | | | | | | | n | | 107 | 117 | 113 | 113 | 105 | | Mean (SD) | | 34.9 (46.00) | 42.9 (54.85) | 33.2 (63.85) | 32.5 (70.56) | 24.8 (54.38) | | Median | | 28.0 | 35.8 | 22.6 | 20.0 | 13.9 | | Min, Max | | -66, 183 | -56, 250 | -53, 300 | -55, 358 | -67, 267 | | 95% CI of Mean | | 26.1, 43.7 | 32.9, 53.0 | 21.3, 45.1 | 19.4, 45.7 | 14.3, 35.3 | | Sham Device (N=68) | | | | | | | | Qmax (mL/2s) | | | | | | | | n | 66 | 58 | 61 | 66 | | | | Mean (SD) | 9.15 (2.595) | 10.92 (6.044) | 11.80 (4.724) | 11.13 (3.887) | | | | Median | 9.20 | 10.00 | 11.00 | 10.85 | | | | Min, Max | 5.0, 14.0 | 4.0, 48.0 | 6.0, 35.0 | 4.0, 22.0 | | | | 95% CI of Mean | 8.51, 9.79 | 9.33, 12.51 | 10.59, 13.01 | 10.17, 12.08 | | | | Qmax Change from Baseline | | | | | | | | n | | 56 | 59 | 64 | | | | Mean (SD) | | 1.79 (5.553) | 2.54 (4.794) | 1.90 (3.553) | | | | Median | | 1.00 | 2.50 | 1.35 | | | | Min, Max | | -4.2, 36.5 | -5.9, 23.5 | -4.0, 13.9 | | | | 95% CI of Mean | | 0.31, 3.28 | 1.29, 3.79 | 1.01, 2.78 | | | Table 21. Secondary Analysis: Peak Flow Rate (Qmax) by Visit (ITT Population) The results of the secondary efficacy endpoints for the mITT/IU population are presented in Tables 22 to 25. PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {37} | | Baseline | 2 Weeks | 1 Month | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=109) | | | | | | | | IPSS Total Score | | | | | | | | n | 109 | 107 | 107 | 106 | 105 | 104 | | Mean (SD) | 23.3 (5.11) | 18.0 (6.85) | 14.5 (6.75) | 14.1 (7.52) | 13.4 (6.21) | 14.4 (7.52) | | Median | 23.0 | 19.0 | 14.0 | 14.0 | 14.0 | 14.0 | | Min, Max | 13, 34 | 1, 31 | 1, 33 | 2, 33 | 2, 30 | 0, 31 | | 95% CI of Mean | 22.3, 24.2 | 16.7, 19.3 | 13.2, 15.8 | 12.6, 15.5 | 12.2, 14.6 | 12.9, 15.8 | | IPSS Total Score Change from Baseline | | | | | | | | n | | 107 | 107 | 106 | 105 | 104 | | Mean (SD) | | -5.2 (7.47) | -8.7 (7.32) | -9.1 (8.01) | -9.8 (6.87) | -8.8 (7.84) | | Median | | -4.0 | -8.0 | -9.5 | -10.0 | -8.0 | | Min, Max | | -31, 11 | -30, 12 | -32, 9 | -29, 7 | -27, 7 | | 95% CI of Mean | | -6.6, -3.7 | -10.1, -7.3 | -10.6, -7.5 | -11.1, -8.5 | -10.3, -7.3 | | Sham Device (N=57) | | | | | | | | IPSS Total Score | | | | | | | | n | 57 | 56 | 56 | 57 | | | | Mean (SD) | 22.7 (4.60) | 17.4 (7.27) | 16.2 (7.52) | 18.0 (7.87) | | | | Median | 23.0 | 19.0 | 17.0 | 20.0 | | | | Min, Max | 14, 31 | 2, 30 | 1, 32 | 1, 31 | | | | 95% CI of Mean | 21.5, 23.9 | 15.5, 19.4 | 14.2, 18.2 | 15.9, 20.1 | | | | IPSS Total Score Change from Baseline | | | | | | | | n | | 56 | 56 | 57 | | | | Mean (SD) | | -5.3 (7.94) | -6.4 (8.23) | -4.7 (8.61) | | | | Median | | -3.5 | -5.0 | -4.0 | | | | Min, Max | | -24, 14 | -27, 17 | -29, 15 | | | | 95% CI of Mean | | -7.4, -3.1 | -8.6, -4.2 | -7.0, -2.4 | | | The 95% CIs are constructed based on t-distribution. For subjects treated with BPH medications or those who undergo removal of the Spring device (not related to a device-related AE) at any time from post-procedure through the 12-month study period, IPSS values recorded prior to the use of BPH medications or Spring device removal are carried forward to all subsequent visits through the 12-month visit. For subjects who undergo removal of the Spring device due to a device-related AE, the Baseline Value Carried Forward approach is applied. No imputation is performed for other missing IPSS scores. Table 22. Secondary Analysis: IPSS Total Score by Visit (mITT/IU Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {38} | Zenflow Spring System (N=109) | | | --- | --- | | | Zenflow Spring System (N=109) | | 6 Months | | | n | 105 | | Responder Rate - n/N (%) | 69/105 (65.7%) | | 95% CI of Responder Rate | 56.2%, 74.1% | | 12 Months | | | n | 104 | | Responder Rate - n/N (%) | 64/104 (61.5%) | | 95% CI of Responder Rate | 51.9%, 70.3% | A responder is a subject whose IPSS score improves at least 30% from baseline. The 95% CIs are constructed based on the Wilson score method. For subjects treated with BPH medications or those who undergo removal of the Spring device (not related to a device-related AE) at any time from post-procedure through the 12-month study period, IPSS values recorded prior to the use of BPH medications or Spring device removal are carried forward to all subsequent visits through the 12-month visit. For subjects who undergo removal of the Spring device due to a device-related AE, the Baseline Value Carried Forward approach is applied. No imputation is performed for other missing IPSS scores. Table 23. Secondary Analysis: Proportion of Subjects Achieving ≥ 30% Improvement From Baseline in IPSS Score at 6 and 12 Months (mITT/IU Population) | | 2 Weeks | 1 Month | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=109) | | | | | | | IPSS Total Score Percent Change from Baseline | | | | | | | n | 107 | 107 | 106 | 105 | 104 | | Mean (SD) | -20.0 (32.59) | -36.1 (30.65) | -38.2 (32.53) | -41.4 (26.06) | -37.3 (32.83) | | Median | -16.7 | -38.7 | -45.3 | -41.9 | -38.5 | | Min, Max | -96, 73 | -94, 75 | -94, 39 | -91, 30 | -100, 39 | | 95% CI of Mean | -26.3, -13.8 | -41.9, -30.2 | -44.5, -32.0 | -46.5, -36.4 | -43.7, -30.9 | | Sham Device (N=57) | | | | | | | IPSS Total Score Percent Change from Baseline | | | | | | | n | 56 | 56 | 57 | | | | Mean (SD) | -21.0 (34.92) | -26.3 (35.93) | -18.3 (37.63) | | | | Median | -16.7 | -23.4 | -17.4 | | | | Min, Max | -92, 93 | -96, 113 | -96, 100 | | | | 95% CI of Mean | -30.4, -11.7 | -35.9, -16.7 | -28.3, -8.3 | | | | Difference in Mean (95% CI) | 1.0 (-9.9, 11.9) | -9.7 (-20.3, 0.9) | -19.9 (-31.1, -8.7) | | | Table 24. Secondary Analysis: Percent Change from Baseline in IPSS Total Score by Visit (mITT/IU Population) PMA P250007: FDA Summary of Safety and Effectiveness Data (SSED) {39} | | Baseline | 2 Weeks | 1 Month | 3 Months | 6 Months | 12 Months | | --- | --- | --- | --- | --- | --- | --- | | Zenflow Spring System (N=109) | | | | | | | | Qmax (mL/2s) | | | | | | | | n | 108 | 88 | 96 | 92 | 96 | 87 | | Mean (SD) | 9.49 (2.717) | 12.58 (3.986) | 13.00 (5.269) | 12.53 (5.178) | 12.00 (5.455) | 11.57 (4.805) | | Median | 9.20 | 12.00 | 12.00 | 11.85 | 11.00 | 10.00 | | Min, Max | 5.0, 15.0 | 5.0, 26.0 | 3.0, 30.0 | 4.0, 31.0 | 4.0, 33.0 | 4.3, 26.5 | | 95% CI of Mean | 8.97, 10.00 | 11.73, 13.42 | 11.93, 14.07 | 11.46, 13.60 | 10.89, 13.11 | 10.55, 12.60 | | Qmax Change from Baseline | | | | | | | | n | | 87 | 96 | 92 | 95 | 87 | | Mean (SD) | | 3.02 (3.859) | 3.60 (4.940) | 3.01 (5.391) | 2.52 (5.747) | 2.05 (4.848) | | Median | | 2.70 | 3.00 | 2.20 | 1.90 | 1.20 | | Min, Max | | -5.3, 12.0 | -6.4, 20.0 | -7.0, 21.6 | -7.5, 23.6 | -8.9, 16.0 | | 95% CI of Mean | | 2.19, 3.84 | 2.60, 4.60 | 1.89, 4.13 | 1.35, 3.69 | 1.02, 3.08 | | Sham Device (N=57) | | | | | | | | Qmax (mL/2s) | |… --- **Source:** [https://fda.innolitics.com/device/P250007](https://fda.innolitics.com/device/P250007) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. 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