Who is the manufacturer of Hemospray Endoscopic Hemostat?

Wilson-Cook Medical, Inc. filed the De Novo classification request for Hemospray Endoscopic Hemostat (DEN170015).

What is the FDA product code for Hemospray Endoscopic Hemostat?

QAU. It is classified under 21 CFR 878.4456 as a Class 2 device in the General, Plastic Surgery panel.

What is the regulatory pathway for Hemospray Endoscopic Hemostat?

De Novo classification (submission type: Direct).

Who can help prepare an FDA De Novo submission like Hemospray Endoscopic Hemostat?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA De Novo submissions. See https://innolitics.com/services/regulatory/ or contact https://innolitics.com/contact.

Hemospray Endoscopic Hemostat

DEN170015 · Wilson-Cook Medical, Inc. · QAU · May 7, 2018 · General, Plastic Surgery

Device Facts

Record ID	DEN170015
Device Name	Hemospray Endoscopic Hemostat
Applicant	Wilson-Cook Medical, Inc.
Product Code	QAU · General, Plastic Surgery
Decision Date	May 7, 2018
Decision	DENG
Submission Type	Direct
Regulation	21 CFR 878.4456
Device Class	Class 2
Attributes	Therapeutic

Intended Use

The COOK Hemospray® Endoscopic Hemostat is used for hemostasis of non-variceal gastrointestinal bleeding.

Device Story

Hemospray® is a prescription endoscopic hemostatic device consisting of a bentonite powder agent and a CO2-powered delivery system. The physician inserts a polyethylene catheter through an endoscope accessory channel to the bleeding site. Upon trigger activation, CO2 propels the bentonite powder onto the bleeding surface. The powder absorbs fluid, swells, and forms a mechanical barrier to achieve hemostasis. Used in clinics or hospitals by gastroenterologists, the device provides rapid, non-contact hemostasis, particularly useful for diffuse bleeding, difficult-to-reach anatomical locations, or as a bridge to definitive treatment in hemodynamically unstable patients. It avoids direct tissue contact, reducing collateral injury risk compared to traditional modalities like clips or cautery. Benefits include ease of use, repeatability, and effectiveness in coagulopathic patients. Potential risks include bowel over-distension, perforation, obstruction, or embolization.

Clinical Evidence

No clinical data provided. Evidence basis for De Novo classification includes in vivo performance testing in clinically relevant models of GI bleeding and non-clinical performance testing to demonstrate mechanical integrity, functionality, and safety endpoints (thromboembolic events, toxicity, tissue trauma, obstruction, perforation).

Technological Characteristics

Materials: Bentonite powder (aluminum phyllosilicate clay) and polyethylene delivery catheter. Energy: Pressurized CO2 cartridge. Form factor: 220cm catheter (7Fr or 10Fr). Connectivity: Standalone. Sterilization: Gamma irradiation. Algorithm: None (mechanical delivery).

Indications for Use

Indicated for patients experiencing non-variceal gastrointestinal bleeding requiring endoscopic hemostasis.

Regulatory Classification

Identification

A hemostatic device for intraluminal gastrointestinal use is a prescription device that is endoscopically applied to the upper and/or lower gastrointestinal tract and is intended to produce hemostasis via absorption of fluid or by other physical means.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) The device must be demonstrated to be biocompatible. (2) Performance data must support the sterility and pyrogenicity of the device. (3) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life. (4) In vivo performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The testing must evaluate the following: (i) The ability to deliver the hemostatic material to the bleeding site; (ii) The ability to achieve hemostasis in a clinically relevant model of gastrointestinal bleeding; and (iii) Safety endpoints, including thromboembolic events, local and systemic toxicity, tissue trauma, gastrointestinal tract obstruction, and bowel distension and perforation. (5) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be evaluated: (i) Materials characterization of all components must demonstrate the device meets established specifications, which must include compositional identity and purity, characterization of impurities, physical characteristics, and reactivity with fluids. (ii) Performance testing must demonstrate the mechanical integrity and functionality of the system used to deliver the device and demonstrate the device meets established specifications, including output pressure for propellant-based systems. (6) Labeling must include: (i) Information identifying and explaining how to use the device and its components; and (ii) A shelf life.

Related Devices

K234131 — Resolv Endoscopic Hemostat System · Hemostasis, LLC · Jul 26, 2024
K240994 — Nexpowder · Nextbiomedical Co., Ltd. · Nov 27, 2024
K190677 — EndoClot · Endoclot Plus Co., Ltd. · Jan 29, 2021
K202929 — Nexpowder · Nextbiomedical Co., Ltd. · Sep 16, 2022

Submission Summary (Full Text)

{0}------------------------------------------------ #### DE NOVO CLASSIFICATION REQUEST FOR HEMOSPRAY® ENDOSCOPIC HEMOSTAT #### REGULATORY INFORMATION FDA identifies this generic type of device as: Hemostatic device for intraluminal gastrointestinal use: A hemostatic device for intraluminal gastrointestinal use is a prescription device that is endoscopically applied to the upper and/or lower gastrointestinal tract and is intended to produce hemostasis via absorption of fluid or by other physical means. NEW REGULATION NUMBER: 21 CFR 878.4456 CLASSIFICATION: Class II PRODUCT CODE: OAU #### BACKGROUND DEVICE NAME: Hemospray® Endoscopic Hemostat SUBMISSION NUMBER: DEN170015 DATE OF DE NOVO: March 9, 2017 CONTACT: Wilson-Cook Medical, Inc. 4900 Bethania Station Road Winston-Salem, NC 27105 #### INDICATIONS FOR USE The COOK Hemospray® Endoscopic Hemostat is used for hemostasis of non-variceal gastrointestinal bleeding. #### LIMITATIONS The sale, distribution, and use of the Hemospray® Endoscopic Hemostat is restricted to prescription use in accordance with 21 CFR 801.109. Please refer to the labeling of the device for a complete list of warnings, precautions, and contraindications. Limitations on device use include the following statements in the Instructions for Use: Contraindication for gastrointestinal endoscopy should also be a contraindication for the use of Hemospray®. Hemospray® Endoscopic Hemostat is also contraindicated in patients who have {1}------------------------------------------------ gastrointestinal fistulas, are suspected of having a gastrointestinal perforation, or are at high risk of gastrointestinal perforation during endoscopic treatment. ## DEVICE DESCRIPTION (b) The Hemospray® Endoscopic Hemostat is a prescription use device consisting of a hemostatic agent and a delivery system. The hemostatic agent is (b) (4) | bentonite powder, a naturallysourced aluminum phyllosilicate clay. The delivery system is an endoscopic accessory used for spraying the powder onto the bleeding surface. The delivery device consists of a 220cm polyethylene application catheter, a handle with a pressurized CO2 cartridge, and a powder chamber containing approximately 20g of the Hemospray® material is propelled through the application catheter by release of CO2 from the cartridge located in the device handle. A trigger valve with an activation button allows the physician to control the amount of powder delivered to the affected area. Each actuation of Hemospray® delivers of CO2 and (b) gram of (b) (4) bentonite. Use of the complete 20-gram canister can produce a volume increase within the lumen of the bowel of 3 liters. In the presence of blood, the (b) (4) bentonite may swell 10-15% in volume. The delivery system is offered in two configurations (i.e., two different outer diameters of the powder delivery catheter). The HEMO-7 version is used with a 2.8mm endoscope accessory channel, and the HEMO-10 version is used in a 3.7mm endoscope accessory channel. Image /page/1/Picture/4 description: This image shows a medical device with several labeled parts. The device has a handle, a CO2 primer, a CO2 cartridge, and a regulator. There is also a trigger valve, an on/off valve, a powder canister, and a 7 FR or 10 FR PE delivery catheter. {2}------------------------------------------------ ## SUMMARY OF NONCLINICAL/BENCH STUDIES The sponsor conducted a series of non-clinical performance tests to demonstrate that the Hemospray® Endoscopic Hemostat would perform as anticipated for its intended use population. ## BIOCOMPATIBILITY The patient-contacting materials of the Hemospray® Endoscopic Hemostat include the (b) (4) bentonite powder and the polyethylene delivery catheter. Hemospray® powder is classified as an implant with prolonged tissue contact and indirect contact with blood. The following biocompatibility testing was completed on the Hemospray® powder in accordance with FDA's guidance document entitled "Use of ISO 10993-1, 'Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process": cytotoxicity, irritation, sensitization, acute systemic toxicity, materials mediated pyrogenicity and hemolysis testing. The subchronic toxicity and implantation endpoints were evaluated in a clinically relevant porcine gastric bleeding animal study. Genotoxicity was evaluated through chemical characterization, toxicological risk assessment and establishment of heavy metal purity specifications. All studies were conducted in compliance with GLP requirements and testing was completed on the final sterilized device. All tests met the acceptance criteria and were supportive of the overall biocompatibility conclusion that the Hemospray® product is expected to be biocompatible when used as indicated. A summary of the biocompatibility testing completed can be found below in Table 1. The delivery catheter is classified as an externally communicating device with less than 24-hours tissue contact. The following biocompatibility testing was completed on the delivery catheter: cytotoxicity, irritation and sensitization. A summary of the biocompatibility testing completed on the delivery catheter can be found below in Table 2. | Biocompatibility Endpoint | Method and Purpose | Result | |-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------|-------------------------------| | Cytotoxicity | ISO 10993-5: MEM Elution Study used to evaluate device extracts for cytotoxicity risks. | Non-cytotoxic | | Sensitization | ISO 10993-10: Guinea Pig Maximization Sensitization Test used to evaluate device extracts for dermal sensitization risks. | Non-sensitizer | | Irritation | ISO 10993-10: Intracutaneous Irritation Test used to evaluate device extracts for irritation risks. | Non-irritant | | Acute Systemic Toxicity | ISO 10993-11: Acute systemic toxicity study used to evaluate device extracts for systemic toxicity risks. | No acute systemic toxicity | | Material mediated pyrogenicity | USP <151>: Rabbit pyrogen test used to evaluate device extracts for pyrogenicity risks. | Non-pyrogenic | | Hemolysis | ASTM: F756: Hemolytic study used to evaluate device extracts for hemocompatibility risks. | Non-hemolytic | | | Table 1. Biocompatibility Testing/Assessment Completed on Hemospray ® Powder | |--|------------------------------------------------------------------------------| |--|------------------------------------------------------------------------------| {3}------------------------------------------------ | Genotoxicity | Genotoxicity risks were evaluated through chemical characterization, toxicological risk assessment and establishment of heavy metal purity specifications. | Genotoxicity risks mitigated | |--------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------| | Subchronic Toxicity and implantation (Animal study) | GLP porcine gastric bleeding model used to evaluate the Hemospray® product of local and systemic toxicity risks in a clinically relevant animal model. | No local or systemic toxicity | Table 2. Biocompatibility Testing/Assessment completed on Hemospray® Delivery Device | Biocompatibility Endpoint | Method and Purpose | Result | |------------------------------|---------------------------------------------------------------------------------------------------------------------------------|--------------------| | Cytotoxicity | ISO 10993-5: MEM Elution Study used to evaluate device extracts for cytotoxicity risks. | Non- cytotoxic | | Sensitization | ISO 10993-10: Guinea Pig Maximization Sensitization Test used to evaluate device extracts for dermal sensitization risks. | Non- sensitizer | | Irritation | ISO 10993-10: Intracutaneous Irritation Test used to evaluate device extracts for irritation risks. | Non-irritant | ### SHELF LIFE/STERILITY Sterilization validation, packaging validation, and shelf life testing completed for the device can be found below in Table 3. Table 3. Sterilization Validation, Packaging Validation, and Shelf Life Testing Overview for Hemospray® Endoscopic Hemostat | Test | Purpose | Result | |-------------------------------------------------------------------------|-----------------------------------------------------------------------------------|--------| | Sterilization Validation ISO 11137:2006/AAMI TIR 33:2005 | Verify product sterility (gamma irradiation) | Passed | | Packaging Validation Visual Inspection | Visual assessment of product packaging to ensure no defects | Passed | | Packaging Validation Dye Leak Test (ASTM F 1929 (R2012), (R2015)) | Demonstrate that the packaging is not compromised | Passed | | Packaging Validation Burst Testing (ASTM F 1140-07, R 2012) | Assess the strength of the packaging seal | Passed | | Shelf Life - Device Stability Visual Inspection | Visual assessment of product to ensure that it is not compromised | Passed | | Shelf Life - Device Stability Functional Testing | Evaluate the ability of the device to meet functional requirements after aging | Passed | ### MAGNETIC RESONANCE (MR) COMPATIBILITY Hemospray® has not been evaluated for safety and compatibility in the MR environment. It has not been tested for heating, migration, or image artifact in the MR environment. {4}------------------------------------------------ Hemospray® powder is composed of naturally occurring bentonite clay, which may contain elements containing metals. The safety of Hemospray® in the MR environment is unknown. Scanning a patient who has this device may result in patient injury or image artifact. No MR safety, device-related adverse effects have been observed in clinical use. ## PERFORMANCE TESTING - BENCH A summary of the performance bench testing completed on the Hemospray® Endoscopic Hemostat can be found below in Table 4. | Test | Purpose | Result | |-----------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------| | Output pressure | Demonstrate that the output pressure at the catheter tip and at the recommended use distance is below the specified threshold and therefore mitigates the risk of powder entering the bloodstream | Passed | | Functional testing | Demonstrate that the user can set up the device for use, insert and remove the device from a compatible endoscope, adjust the system to reach the targeted site, detach and reattach catheters during use, press the delivery button, and deploy powder to the targeted site with the Hemospray® device | Passed | | Rupture Testing | Demonstrate that the Hemospray® handle will not rupture at or below working pressures | Passed | | Human Factors Testing | Demonstrate that the Hemospray® device has an acceptable torque to detach/reattach catheters, torque to open/close valve and force to press button | Passed | | Powder Density | Demonstrate that the Hemospray® device can deliver powder to the desired location, that the catheter will not clog, and that powder will not be delivered intermittently | Passed | | Cartridge Integrity | Demonstrate that the Hemospray® introducer component meets functional requirements after simulated shipping test | Passed | | Ex vivo tissue trauma | Evaluate local effects of Hemospray® when delivery catheter is positioned at recommended use distance | No significant pathological alterations were observed. Hemospray® did not penetrate the mucosal layer | Table 4. Performance Bench Testing Overview of Hemospray® Endoscopic Hemostat ## MATERIALS CHARACTERIZATION A summary of the materials characterization completed on the Hemospray® Endoscopic Hemostat can be found below in Table 5. {5}------------------------------------------------ | Test | Purpose | Result | |-----------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------| | Mineral phase identification and quantification by x-ray diffraction (XRD) on a per-lot basis | Establish the compositional identity and purity of Hemospray® powder. Measurements will ensure the compositional identity and purity of each lot is within specifications. | Compositional identity and purity were established and allowed lot-to-lot acceptance criteria to be set. | | Free Swell Test and Moisture Content | Establish that Hemospray® powder's extent of water absorption and moisture content meet specifications. Measurements will ensure the swelling characteristics and moisture content of each lot are within specifications. | Passed | | Extraction in simulated gastric fluid for lead and arsenic on a per lot basis | Demonstrate that bioavailable lead and arsenic levels are within safe limits for each lot per limits identified in the USP monograph for Bentonite. | Passed | | Particle Size Characterization | Characterize the particle size distribution of Hemospray® powder to ensure that each lot can be adequately sprayed. | Results demonstrate consistent particle size distribution across lots. | Table 5. Materials Characterization Overview of Hemospray® Endoscopic Hemostat # PERFORMANCE TESTING - ANIMAL The safety and effectiveness of Hemospray® Endoscopic Hemostat was evaluated in a GLP porcine gastric bleeding model. The study is summarized below: Table 6. Performance Animal Testing Overview of Hemospray® Endoscopic Hemostat | Test | Purpose | Method | Results | |-------------------------|-----------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | GLP Porcine Study | Assess hemostatic ability (effectiveness) and safety of the device | Design: Gastric bleeding model. Animals: 6 Hemospray® treated, 3 sham control. Duration: 10-day follow-up followed by termination | Acute hemostasis was achieved in all animals in the treatment group (6/6). One control animal (1/3) and two (2/6) treatment group animals showed re-bleeding 8 to 10 days post-operatively. The re-bleeding observed were most likely associated with limitations of the chosen surgical procedure. Histopathological evaluation of the device application site did not reveal any important histological differences between treatment group and control group animals. No evidence of Hemospray® powder was | {6}------------------------------------------------ | | Endpoints: gross and histologic assessment of regional and systemic effects of powder/treatment | observed in any local or regional tissue sections of the gastric surgical site or the regional lymph nodes. No Hemospray® powder particles were observed to have been embedded in any tissue layers in any of the three histological sections collected at and around the treatment site. | |--|----------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| |--|----------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| Results of the animal study suggest that the Hemospray® Endoscopic Hemostat is effective at achieving initial hemostasis in a worst-case gastric bleeding model (Forrest 1a and 1b peptic ulcer tvpe bleeding). This study does not demonstrate safety/effectiveness in large area low-pressure bleeding where the probability of embolization may be more likely nor did it assess the potential rate of delayed re-bleeding. ## SUMMARY OF CLINICAL INFORMATION Wilson-Cook Medical, Inc. has sponsored a pre-market pilot study, a survey and 2 postmarket clinical studies of Hemospray® to date, all performed outside the United States (OUS). The pilot study was a "first-in-human" feasibility study to determine performance and safety issues associated with the endoscopic use of Hemospray® powder as a hemostatic material to treat bleeding peptic ulcers. This study was conducted in Hong Kong, China from 2009 to 2010. The Survey to Evaluate the Application of Hemospray® in the Luminal Tract (SEAL), was conducted in Canada, Denmark, England, France, Germany, Italy and Holland. The first post-market study. Hemostasis of Active GI Luminal Tract Bleeding (HALT) trial. was conducted in the European Union (EU). It was intended to study the safety and effectiveness of Hemospray® in treating upper gastrointestinal bleeds (UGIB), specifically Forrest 1a and 1b actively bleeding ulcers. Peptic ulcers are the most common cause of UGIB and are usually classified as spurting/pulsatile (1a) or oozing (1b) according to the Forrest scale. They account for up to 50% of peptic ulcer bleeds. The study began in 2011 with an intent to enroll 80 patients; 64 patients have been enrolled to date. The HALT study continues to enroll patients in the EU and Canada. Finally, the second post-market study, APPROACH (A Prospective Observational Cohort Study of Hemospray® for Lower Gastrointestinal Hemorrhage), was conducted in Canada and designed to collect safety and performance data on non-variceal lower gastrointestinal bleeding (NVLGIB). APPROACH has recently completed enrolling its entire complement of 50 patients at 4 Canadian sites. The results of all the studies are presented below. ## PILOT STUDY This pilot clinical trial was designed as a single-center, early feasibility study of Hemospray® powder for the treatment of bleeding peptic ulcers. The aim of the study was to investigate the safety and effectiveness of Hemospray® in achieving acute hemostasis in peptic ulcer bleeding in subjects diagnosed with Forrest 1a or 1b bleeding peptic ulcers. The protocol for this prospective trial was approved by the ethics committee of the faculty of medicine of the Chinese University {7}------------------------------------------------ of Hong Kong. China and conducted in accordance with the Declaration of Helsinki. International Conference on Harmonization, Good Clinical Practices, and other regulations in force in Hong Kong. Written informed consent was obtained from all patients were to undergo upper GI endoscopy within approximately 24 hours of hospital admission. Each patient was allowed up to 2 applications of Hemospray® (potentially using multiple canisters during each application) during the index procedure, not exceeding a total of 150 g. Recurrent bleeding was monitored post-procedure and at a second-look endoscopy (72 hours posttreatment) was conducted on all patients. Patients were contacted by phone at 30 days to monitor the occurrence of any serious adverse events and mortality. The safety and performance outcome measures of this study were: Primary safety endpoint: - The incidence of procedural and treatment-related serious adverse events for subjects . treated with Hemospray®. Primary effectiveness endpoint: - Proportion of subjects with acute (procedural) hemostasis. . - Rate of recurrent bleeding within 72 hours of the application of Hemospray® Secondary Outcome Measures - Severe adverse events and mortality within 30 days of the study procedure . - . Surgery required for failure to achieve hemostasis within 72 hours Rate of hemostasis, rate of recurrent bleeding, need for surgical intervention, treatment-related and procedure-related serious adverse events and major adverse events (e.g., arterial embolization, allergic reaction, bowel obstruction) were also assessed. Twenty patients were enrolled in the study. An interim analysis was conducted on data collected from the first 10 patients. Since no major adverse events related to the Hemospray® powder or delivery catheters were reported. 10 additional patients were enrolled. The study consisted of 18 males and 2 females. Mean age was 60.2 years (range 37-85 y). The first patient was enrolled in the study on November 17, 2009 and the last patient was enrolled on August 27, 2010. The final follow-up visit was on September 27, 2010. All 20 patients included in this study presented with melena at hospital admission, 7 of whom also had concurrent hematemesis. Nineteen patients were diagnosed with a Forrest 1b ulcer and 1 patient had Forrest 1a bleeding. Most ulcers were in the duodenum 14 (70%) and the remaining 6 (30%) were in the stomach. A single application of Hemospray® was used in 17 (85%) patients, and two applications were used in 3 (15%) patients. The number of syringes of Hemospray® used for each patient ranged between 1 and 7, with most patients (13/20, 65%) receiving only 1 syringe (20g). Of the remaining 7 patients, 5 received 2 syringes, one patient received 4 syringes, and one patient received 7 syringes. {8}------------------------------------------------ ### Results: Endoscopic application of Hemospray® onto the ulcer bleeding site was successfully performed in all patients. Acute hemostasis was achieved in 19 of 20 patients (95%). There were no treatment-related or procedure-related serious adverse events. All patients were stable after the procedure and recovered uneventfully. The one patient in which acute hemostasis was not achieved was treated with 7 syringes of Hemospray® or 140 grams in one application. This patient was then treated according to institutional standard of care (endoscopic epinephrine injection and hemostasis clips) in 3 additional unsuccessful attempts to achieve endoscopic hemostasis and was referred for angiography during which a pseudoaneurysm was identified in the artery feeding the ulcer site. Ultimately, TAE (trans-arterial embolization) of the feeding artery was required to stop bleeding in this patient. The patient was contacted at 30 days and reported no serious adverse events. Of the 19 patients in which acute hemostasis was achieved, sustained hemostasis as defined by the study was observed in 17 (89.5%) patients through 72 hours. Two patients met the study definition of recurrent bleeding or re-bleeding within 72 hours. However, in both patients, no active bleeding was observed at the treated lesion sites at the planned second-look endoscopy. Both patients reported no adverse event or serious adverse event at 30-day follow-up. ## Safety outcome: The Hemospray® powder was found to have been eliminated from the stomach and duodenum in all patients at the second-look endoscopy, conducted on Day 2 for one patient and Day 3 for all others. None of the patients, including the patient who received 140 grams or 7 syringes reported any adverse issues with passage of the powder through the gastrointestinal tract (e.g., no bowel obstruction). All patients were stable after the procedure and discharged uneventfully. There was no mortality reported during the 30-day follow-up. No treatment-related or procedurerelated serious adverse events and no major adverse events (e.g., embolization, bowel obstruction, or allergic reaction) were reported. While there were no reports of serious adverse events related to either the treatment or the procedure, 5 cases of non-device related serious adverse events were reported. These included 4 cases of prolonged hospitalization: 2 due to upper respiratory tract infection, 1 due to altered liver function and psychotic depression, and 1 patient who required more time to recover and regain stable blood values. The fifth event was the diagnosis of adenocarcinoma that was initially diagnosed as a gastric ulcer during the Hemospray® treatment procedure. In this last patient, a large gastric ulcer oozing from the base was found during endoscopy. There were some features suggestive of malignancy and biopsy was performed. The bleeding was successfully controlled by Hemospray®, and no Hemospray® powder was observed at the 72-hour endoscopy at the treatment site. Histology subsequently confirmed malignancy, and this patient was referred to a medical oncologist for further management. The only observations of relevance were clogging of the Hemospray® application catheter, but in each case a new catheter was used and the procedure completed. # SURVEY TO EVALUATE THE APPLICATION OF HEMOSPRAY IN THE LUMINAL TRACT (SEAL) Wilson-Cook Medical, Inc. initiated the post-market Survey to Evaluate the Application of Hemospray® in the Luminal Tract (SEAL) to collect limited, non-protected health information {9}------------------------------------------------ and data on the Wilson-Cook Medical, Inc. Hemospray® Endoscopic Hemostat as part of a limited marketing release OUS. The information was used to develop educational materials for physicians new to this technology. Hemospray® used endoscopically by gastroenterologists provided effective acute hemostasis in the most common types of gastrointestinal (GI) bleeding, including Forrest 1a and 1b bleeding peptic ulcers. As a requirement of participation in the SEAL registry, all physician participants were trained on the use of the Hemospray® kit by Wilson-Cook Medical, Inc. personnel. Training included discussion of hemostasis techniques, appropriate intended use and product labeling in the countries where the evaluation took place, and hands-on experience with the Hemospray® device. Each participating physician group was assigned a unique sign-on to access an electronic data capture form hosted on a secure internet portal. All cases entered into the database were numbered sequentially in the order of entry. No queries or audits to identify and correct missing data were performed. Summaries generated from the collected information were, therefore, constrained by the scope of the information collected, and are limited to counts of cases, common location of bleeding sites, severity of the bleeding treated, and other methods to achieve hemostasis if used in conjunction with Hemospray®. Complaints and adverse events were to be reported directly to the manufacturer. Ninety-two patients treated in Canada, Denmark, England, France, Germany, Italy and Holland were registered in this survey. Two patients had no data entered in the electronic database by the site other than age and sex. In a third patient, the CO2 cartridge in the Hemospray® delivery system was found to be defective so the device was not used and the patient was not treated with Hemospray®. These 3 patients were excluded from analysis. Therefore, evaluable data from 89 patients were available for analysis. Eight-four percent (84%) of patients were over the age of 50 (n = 75), and 71% (n = 63) were male. Acute hemostasis was achieved in all (100%) cases. Approximately 98% of the bleeding sites were in the upper GI tract and were identified in the duodenum (n = 38), stomach (n = 29), and esophagus (n = 20). Peptic ulcers constituted most cause of GI bleeding treated with Hemospray® (n = 40; 45%). Of the 40 patients with peptic ulcers, 16 were Forrest 1a bleeds (spurting or pulsatile), 19 were Forrest Class 1b (oozing), 3 were Forrest 2b (adherent clot), and 2 patients were unclassified. In one Forrest 2b case, a procedural video confirmed the clot was removed prior to treatment with Hemospray®. It is not known if the other 2 cases were treated in a similar fashion. Other conditions treated with Hemospray® included: bleeding after endoscopic mucosal resection or dissection (n = 9; 10%); diffuse bleeding from gastric malignancy (n = 8; 9%); Mallory-Weiss tears (n = 6; 7%); and upper GI post-polypectomy bleeding (n = 5; 6%); Hemospray® was used successfully in the colon for acute hemostasis in 2 cases. Fifty-one (51) patients (57%) were successfully treated with Hemospray® alone, and the remaining 38 patients (43%) were successfully treated with Hemospray® as an adjunct to other standard of care methods. Hemospray® was identified as the final hemostasis treatment in 24 of 38 cases where more than one other method was used. In 5 patients, Hemospray® was used as the initial treatment and was followed by alternate methods including epinephrine injection, argon-plasma coagulation, bi-polar electrocautery, and hemoclips. In 9 patients, the order of use was unclear. Hemospray® was used as a single modality in 51 patients. Of the 51 patients treated with Hemospray® alone, 11 were diagnosed with Forrest 1a bleeds, 38 with Forrest 1b, and 2 with Forrest 2b. Acute hemostasis was achieved with Hemospray® alone in all 51 of {10}------------------------------------------------ these patients. The remaining 38 patients were treated with Hemospray® and at least one other modality; 16 of these with Forrest 1a, 19 with Forrest 1b, 1 with Forrest 2b, and 2 were unclassified. Acute hemostasis was achieved in all 38. There were no unanticipated adverse events or serious adverse events attributed to the Hemospray® Endoscopic Hemostat. Holster I.L. et. al., published a study of patients in the SEAL survey with upper gastrointestinal bleeding who were on antithrombotic therapy which included mostly patients on antiplatelet agents and a few on anticoagulation therapy. Patients had 63% initial hemostasis with a 38% rebleeding rate following Hemospray® treatment. ## HEMOSTASIS OF ACTIVE GI LUMINAL TRACT BLEEDING (HALT) STUDY The HALT trial was designed to study the safety and effectiveness of Hemospray® in treating upper GI bleeds (UGIB), specifically Forrest 1a and 1b actively bleeding ulcers. The HALT trial continues to enroll patients in Canada and Europe with a final goal of 80 enrollments. An interim report of the study findings at 64 enrollments is presented as part of this submission. The data lock was instituted on August 24, 2016. The HALT study was initiated with Version 1 of the Hemospray® device (55 psi CO2 canisters), but all sites were converted to the Version 2 device (37 psi CO2 canisters) effective January 2013. There are 10 enrollment sites. | | %(n/N) | |-------------------------------------------------------------------------------|----------------| | Hypertension | 47.6% (30/63a) | | Diabetes | 27.0% (17/63a) | | Patient already hospitalized for another illness when GI bleeding occurred | 10.9% (7b/64) | | Previous treatment(s) for peptic ulcer bleedingc | 22.2% (14/63a) | | Hemostasis clips | 35.7% (5/14) | | Injection | 42.9% (6/14) | | Thermal probe | 28.6% (4/14) | | Upper GI surgery | 0.0% (0/14) | | Other Endoscopic/surgical treatment | 7.1% (1/14) | | Transfusion | 64.3% (9/14) | | IV administration of PPI | 64.3% (9/14) | | Oral administration of PPI | 21.4% (3/14) | | Other Medical treatment | 0.0% (0/14) | | Current symptoms of peptic ulcer bleedingd | 98.4% (62/63a) | | Hematemesis | 22.6% (14/62) | | Hematochezia | 12.9% (8/62) | | Melena | 91.9% (57/62) | ## Table 7: Patient Comorbidities a Data were outstanding at time of data lock for one patient. {11}------------------------------------------------ b Prior hospitalization for chest, abdominal, and loin pain (1); fall(s) (2); syncope related to GI bleed (1); low hemoglobin, chest pain, shortness of breath (1); prior GI bleed (1); loose stools and generally unwell (1). 6 Patients may have more than one treatment on prior admissions for peptic ulcer bleeding. d Patients may have more than one current symptom of peptic ulcer bleeding. | Lesion size (diameter)a,b | | |---------------------------|---------------| | < 1 cm | 32.3% (20/62) | | 1-2 cm | 54.8% (34/62) | | > 2 cm | 12.9% (8/62) | | Lesion locationb | | | Stomach | 25.4% (16/63) | | Duodenum | 74.6% (47/63) | | Forrest classificationb | | | 1a (spurting) | 15.9% (10/63) | | 1b (oozing) | 84.1% (53/63) | Table 8. Baseline Bleed Site Characteristics ª One patient did not have an ulcer diameter measurement. b Data were outstanding at time of data lock for one patient. ## Primary Endpoint The primary effectiveness endpoint is the proportion of patients with further bleeds within 72 hours of the index procedure. Further bleed within 72 hours is defined as persistent bleeding (bleeding at the conclusion of the index endoscopy: 7 patients did not achieve initial hemostasis with Hemospray®) or recurrent bleeding (visualization of bleeding at the treated study lesion [assessed only in patients with successful initial hemostasis]) within 72 hours. ## Table 9. Primary Endpoint | | % (n/N) | |----------------------------------------------------------|----------------| | Patients with further bleeds within 72 hours | 17.2% (11/63a) | | Persistent bleeding after Hemospray application(s) | 11.1% (7/63a) | | Endoscopically-confirmed recurrent bleed within 72 hours | 7.1% (4/56b) | a Data were outstanding at time of data lock for one patient. b Recurrent bleed was only assessed in patients with successful initial hemostasis (i.e., patients without persistent bleeding). To further investigate if demographics or baseline characteristics affected the primary endpoint, persistent bleeding, or early recurrent bleed, a stepwise logistic regression was performed using sex, ulcer location, ulcer diameter, Forrest score, and hypertension as variables (criterion was p<0.3 for inclusion in the model; criterion for removal was p>0.35). No variables were found to significantly affect the primary endpoint of persistent bleeding; however, stepwise logistical regression indicated that patients with Forrest 1a bleeds are more likely to have an early recurrent bleed than patients with Forrest 1b bleeds. Further, patients with Forrest 1a bleeds are {12}------------------------------------------------ more likely to have any recurrent bleed (early or late) than patients with Forrest 1b bleeds based on stepwise logistical regression. ## Secondary Endpoints Secondary endpoints include: proportion of patients with hemostasis at the conclusion of the index procedure (i.e., initial hemostasis), clinical success (i.e., initial hemostasis and no SAE within 72 hours of the index procedure), early recurrent bleed (i.e., recurrent bleeding within 72 hours of the application of Hemospray®), late recurrent bleed (i.e., recurrent bleed occurring 72 hours-30 days), incidence of serious adverse GI events within 30 days of the application of Hemospray®, incidence of serious adverse events within 30 days of the application of Hemospray® and incidence of mortality at 30 days. | | Number | Percent | |---------------------------------------------------------------------------------------|--------|---------| | Patients achieving hemostasis during index endoscopy | 61 | 96.8 | | Successful hemostasis achieved after Hemospray® application | 56 | 88.9 | | Re-bleeding within 72 hours after successful initial hemostasis | 4 | 7.1b | | 30-day all-cause mortality | 2a | 3.2 | | Patients with device-related Serious Adverse Events within 30 days of index procedure | 0 | 0.0 | Table 10. HALT Study Secondary Endpoints 4First patient cause of death was liver failure. Second patient cause of death was pneumonia. b Re-bleeding was only assessed in patients with successful initial hemostasis (n=56). Of the twelve patients with serious adverse events, one patient had an intra-operative perforation reported. This patient died two days post-procedure due to liver failure. Ten patients had clinical signs and symptoms of re-bleeds (seven with confirmed recurrent bleeding at the study lesion site, one which endoscopically confirmed that the initial study lesion was not involved, and two which were not considered to be a recurrent bleed at the study lesion site by the physician and therefore did not have repeat endoscopy performed). Of note, clinical signs and symptoms of rebleed are a common adverse event in patients recently treated for peptic ulcer bleeds. One patient had no signs of re-bleeding, however, developed pneumonia that resulted in death. | Table 11. Adverse Events by Organ System | | | | | | |------------------------------------------|--|--|--|--|--| |------------------------------------------|--|--|--|--|--| | Organ System | 0-3 Days (n) | 4-7 Days (n) | 8-30 Days (n) | |------------------|--------------|--------------|---------------| | Gastrointestinal | 15 | 5 | 5 | | Cardiovascular | 0 | 0 | 1 | | Pulmonary | 0 | 0 | 0 | | Miscellaneous | 4 | 2 | 4 | | | Table 12. Gastrointestinal Events | |--|-----------------------------------| |--|-----------------------------------| | Event | 0-3 Days (n) | 4-7 Days (n) | 8-30 Days (n) | |-------|--------------|--------------|---------------| |-------|--------------|--------------|---------------| {13}------------------------------------------------ | Clinical signs and symptoms of re-bleed | 11 | 5 | 4 | |-----------------------------------------|----|---|---| | Other | 2 | 0 | 1 | | Perforation | 2 | 0 | 0 | Specifically, 11 events of clinical signs and symptoms of re-bleeding in 10 patients and 2 perforations were considered serious adverse events. Of the reports of re-bleeding, two were not considered recurrent bleeds because hemostasis had not been achieved with Hemospray® during the initial procedure. No treatment or repeat endoscopy was performed for either patient and neither patient had further reports of clinical signs and symptoms of re-bleeding throughout the follow-up period. In three additional cases that were not considered recurrent bleeds, correspondence between Wilson-Cook Medical, Inc. and the study physician indicated that the clinical signs and symptoms of re-bleeding were attributable to the original bleed, rather than recurrent bleeding; therefore, additional endoscopy was not performed. None of the signs or symptoms were treated (although one patient was instructed to take an iron supplement), and no further reports of clinical signs or symptoms of re-bleeding were submitted throughout the remainder of the study follow-up. In one case that was not considered recurrent bleeding, it was reported that re-bleed from the treated site was not suspected. One individual with hypotension and melena after normalization of stool color was not re-scoped as the study site reported that the patient was not well enough to undergo repeat endoscopy and the patient's melena had resolved on the same day. The remaining patient with clinical signs and symptoms of re-bleeding did have recurrent bleed with endoscopic confirmation of study lesion involvement, which was treated with epinephrine injection, hemostasis clips, and transfusion. Initial hemostasis was achieved using Hemospray® as a single-modality treatment method in 88.9% (56/63) of cases. Initial hemostasis was defined as patients with hemostasis at the conclusion of the index procedure, where 'index procedure' is considered to be the application of Hemospray® and a 5-minute observation period. Patients that did not achieve initial hemostasis with Hemospray® were treated with hemostasis clips (1 patient), injection (with epinephrine) and hemostasis clips (2 patients), injection and argon beam therapy (1 patient), injection and thermal probe (1 patient), conversion to surgical repair (1 patient is described further in Table 10, HALT Summary Study Data), and proton pump inhibitor (PPI) therapy (1 patient). Subsequent events of perforation and death were reported for 1 patient. Fifty-five patients completed their 30-day follow-up; eight patients exited the study prior to completion of 30-day follow-up. Of these eight, one patient died 2 days after the procedure, and one patient died 18 days after the procedure. Both deaths occurred after surgical intervention, one for bowel perforation and one for re-bleeding, resulting in death from postoperative liver failure and pneumonia, respectively. Six other patients were lost to follow up prior to completing the study follow-up schedule. # A PROSPECTIVE OBSERVATIONAL COHORT STUDY OF HEMOSPRAY™ FOR LOWER GASTROINTESTINAL HEMORRHAGE (APPROACH) The second study is the APPROACH study in Canada. APPROACH is designed to collect safety and performance data on NVLGIB. Although the rate of occurrence and mortality in LGIB is lower than UGIB, bleeding in the lower GI tract can become clinically significant and/or {14}------------------------------------------------ exacerbate existing co-morbidities. This prospective, single-arm, post-market study collected data on the safety and performance of the Hemospray® device when used as a treatment to achieve hemostasis of non-variceal lower GI bleeding. The study enrolled 50 patients at 4 clinical sites in Canada. Patient enrollment and data collection were completed in October and November 2016, respectively. The final site monitoring visit was completed in February 2017. Results are presented below. | | Number | Percent | |--------------------------------------------------------------------------------------|--------|---------| | Number of sites | 4 | na | | Patients enrolled | 50 | na | | Patients achieving hemostasis during index endoscopy | 50 | 100.0 | | Successful hemostasis achieved using Hemospray® | 49a | 98.0 | | Patients with recurrent bleed as defined by the study protocol | 5 | 10.0 | | 30-day all-cause mortality | 1b | 2.0 | | Patients with device-related adverse events within 30 days of the index procedure | 0 | 0.0 | Table 13. APPROACH Study Summary Data a In one patient, hemostasis was not achieved with the initial, single modality use of Hemospray . Hemostasis clips were used also in order to achieve hemostasis. b Includes 1 patient who died within 30 days. Cause of death: gastrointestinal bleeding (site unclear) secondary to pre-existing idiopathic thrombocytopenia. | Table 14. Patient Demographics | | |--------------------------------|--| |--------------------------------|--| | Demographic Characteristic | Reported (n=50) | |-----------------------------------------------|-----------------| | Age (years) | $64.6 \pm 12.5$ | | Mean $\pm$ SD (number of patients, age range) | (50, 37 - 85) | | Sex | | | Male | 72.0% (36/50) | | Female | 28.0% (14/50) | ### Table 15. Pre-procedure Co-Morbid Conditions | Co-morbid Conditions | Percent of Patients (n/N) | |-------------------------------------------------------------------------------------|---------------------------| | Patient already hospitalized for another illness when lower GI bleeding occurred | 8.0% (4/50) | | Previous episodes of GI bleeding | 56.0% (28/50) | | Current symptoms of lower GI bleeding | 52.0% (26/50) a | | Hematochezia | 24.0% (12/50) | | Melena | 8.0% (4/50) | {15}------------------------------------------------ | Chronic anemia | 6.0% (3/50) | |----------------------------------|-------------| | Acute anemia | 6.0% (3/50) | | Positive fecal occult blood test | 18% (9/50) | a Patients may have more than one current symptom of lower GI bleeding. | Hemospray® Use | | Percent of Patients (n/N) | |------------------------------------------------------|---------------------------------------------------------------------------------------------|------------------------------| | Number of bleed sites treated per patient | 1 | 96.0% (48/50) | | | 2 | 4.0% (2/50) | | Index procedural use of Hemospray® | Initial intervention (Hemospray® as monotherapy) | 26.0% (13/50) | | | Supplemental intervention (Hemospray® in conjunction with another intervention) | 40.0% (20/50) | | | Rescue intervention (Hemospray® after failure of prior intervention) | 34.0% (17/50) | | Was Hemospray® applied to bleed site as intended? | Yes | 100% (50/50) | Table 16. Hemospray® Use during Study Procedure The Primary Endpoint is Hemospray -related adverse events occurring within 30 days of the index procedure. Hemospray® related adverse events include, but are not limited to, powder impaction in colon or embolization. | Table 17. Primary Endpoint | - 2017 - 10 10000 | 1986 - 12 | |----------------------------|-------------------|-----------| |----------------------------|-------------------|-----------| | Hemospray® Related Adverse Events within 30 Days of the Index Procedure | Percent of Patients (n/N) | |----------------------------------------------------------------------------|------------------------------| | Yes | 0.0% (0/50) | | No | 100% (50/50) | ## Secondary Endpoints: - · Hemostasis following application of Hemospray® - · Recurrent bleeding within 30 days of the index procedure - · Mortality within 30 days of the index procedure {16}------------------------------------------------ | Endpoints | | Percent of Patients (n/N) | |---------------------------------------------------------|-----|---------------------------| | Hemostasis following application of Hemospray® | Yes | 98.0% (49/50) | | | No | 2.0% (1/50) | | Recurrent Bleeding Within 30 Days of Index Procedure | Yes | 10.0% (5/50) | | | No | 90.0% (45/50) | | Mortality Within 30 Days of Index Procedure | Yes | 2.0% (1/50) | | | No | 98.0% (49/50) | Table 18. Secondary Endpoints Hemostasis was achieved after the index procedural use of Hemospray® as an initial, supplemental, or rescue intervention treatment method in 97.3% of cases. Hemostasis, defined as the absence of persistent bleeding at the conclusion of the index colonoscopy, was achieved in all but one patient who had a visibly oozing or spurting bleed. | | Percent of Data Available Endpoint Since Previous Time Period | | | | | | |-----------|------------------------------------------------------------------|---------------------|-------|-------------------|------------|---------------------------------------| | Period | Patients Eligible for Follow-Upa | Telephone Follow-up | Death | Lost to Follow-up | Withdrawal | Not Eligible for Next Follow-up Visit | | Procedure | 50 | N/A | 0 | 1 | 0 | 0 | | 14-day | 49 | 98.0% (48/49) | 0 | 0 | 0 | 0 | | 30-day | 49 | 98.0% (48/49) | 1 | N/A | N/A | N/A | Table 19. Clinical Follow-up Data a Number of patients eligible = previous number eligible - (death + LTF + withdrawal + not eligible for next follow-up visit). Table 20. Comparison of APPROACH Study Results with American Society of Gastrointestinal Endoscopy (ASGE) Standard of Care | Endpoint | APPROACH Study Results | Standard of Care per ASGE | |--------------------------------------------------|---------------------------|---------------------------| | 30-day Mortality Rate | 2.0% | 2.0-4.0% | | Hemostasis Achieved During Index Endoscopy | 100.0% | 50-100.0% | {17}------------------------------------------------ | Re-bleeding Rate | 10.0% | 18-22.0% | |------------------|-------|----------| |------------------|-------|----------| ## Serious Adverse Events Of the six patients with serious adverse events, one patient died from gastrointestinal bleeding secondary to pre-existing chronic idiopathic thrombocytopenia 27 days after the procedure. Five cases of clinical signs and symptoms of lower GI bleeding were reported in four patients. Two of these cases were confirmed to have a recurrent bleed at the study lesion site, one case was conservatively assumed to be a recurrent bleed at the study lesion site as visual confirmation was not attained, and three cases were considered not to be recurrent bleeds. Two additional postoperative serious adverse events were reported in which clinical signs and symptoms of lower GI bleeding were not noted. | Category | 0-14 Days (N) | 15-30 Days (N) | |------------------|---------------|----------------| | Gastrointestinal | 10 | 1 | | Pulmonary | 0 | 0 | | Cardiovascular | 0 | 0 | | Miscellaneous | 4 | 1 | Table 21. Patient Morbidity Forty-eight patients completed their final follow-up. One patient exited the study prior to completion of the 14-day and 30-day follow-ups. One patient died 27 days after the procedure, as noted above. No other patients were lost to follow up prior to completing the study follow-up schedule. # Literature Summary of Recent Clinical Hemospray® Use An extensive search was performed to identify the existing clinical literature on the recent use of Hemospray®. The search terms "Hemospray" or "TC-325" were used in PubMed and Google Scholar. Only publications in clinical journals were included in the analysis. Non-clinical studies, review articles, conference abstracts, and publications not in English were excluded. Publications that appeared to have overlapping patients with another study were excluded. Treatments of contraindicated bleeding types (e.g., varices or fistulas) were excluded from the analysis. Thirty (30) relevant studies were identified comprising the treatment of 522 patients with Hemospray®. Overall, the hemostasis rate after the use of Hemospray® was 96% and the endoscopically achieved hemostasis rate was 97%. The 30-day gastrointestinal bleeding-related mortality rate was 3%. Four potential device-related adverse events (0.8%) were identified in the literature (2 reports of perforation and 2 reports of aspiration pneumonia); however, none of these events were reported to be directly attributed to the use of Hemospray® in the publications. {18}------------------------------------------------ | | Number | Percent | |---------------------------------------------------------------|--------|---------| | Number of studies | 30 | n/a | | Patients treated | 522 | n/a | | Hemospray® procedures | 532 | n/a | | Successful hemostasis achieved using Hemospray® | 509 | 96% | | Patients achieving hemostasis during index endoscopy | 518 | 97% | | Re-bleeding within 7 days after successful initial hemostasis | 97 | 19% | | Re-bleeding 8-30 days after successful initial hemostasis | 20 | 4% | | 30-day all-cause mortality | 80 | 11% | | 30-day gastrointestinal bleeding mortality | 23 | 3% | | Potential device-related adverse eventsa | 4 | 0.8% | # Table 22. Hemospray® Clinical Literature Summary a Potential device-related adverse events were 2 perforations and 2 cases of aspiration pneumonia. None of these adverse events could be directly attributed to the use of Hemospray®. The literature reports consisted of the following levels of evidence: - . Level II: 12 Registry Derived Studies - Level IV: The remainder of the studies consist of level IV evidence single arm ● retrospective or prospective studies, case series and case reports. For a total of 30 studies in which there were 532 Hemospray® applications, resulting in 96% hemostasis rate and an overall re-bleeding rate of 23%. There were 2 instances of bowel perforation which may have been attributed to the use of Hemospray® and 2 aspiration pneumonias which could not be conclusively attributed to Hemospray®. There were no reports of bowel powder impaction or thromboembolic events. {19}------------------------------------------------ | Study | Patients (n) | Hemospray Applications | Hemostasis after Hemospray Application | Endoscopic Hemostasis | Hemospray Hemostasis Rate | Endoscopic Hemostasis Rate | Rebleeding at risk patients | Rebleeding Events (7d) | Rebleeding Rate (7d) | Rebleeding Events (8-30d) | Rebleeding Rate (8-30d) | |-------------------------------|-----------------|---------------------------|-------------------------------------------------|--------------------------|---------------------------------|----------------------------------|-----------------------------------|---------------------------|-------------------------|---------------------------------|-------------------------------| | Sung 2011 | 19 | 20 | 19 | 19 | 95% | 95% | 19 | 2 | 11% | 0 | 0% | | Chen 2012 | 5 | 6 | 5 | 5 | 83% | 83% | 5 | 1 | 20% | 0 | 0% | | Granata 2013 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Holster 2013 | 15 | 15 | 12 | 14 | 80% | 93% | 15 | 5 | 33% | 0 | 0% | | Leblanc 2013 | 12 | 12 | 12 | 12 | 100% | 100% | 12 | 0 | 0% | 0 | 0% | | Smith 2013 | 4 | 4 | 4 | 4 | 100% | 100% | 4 | 0 | 0% | 0 | 0% | | Smith 2013 (SEAL) | 62 | 63 | 56 | 61 | 89% | 97% | 61 | 8 | 13% | 0 | 0% | | Soulellis 2013 | 4 | 4 | 4 | 4 | 100% | 100% | 4 | 0 | 0% | 0 | 0% | | Appleby 2014 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Chen 2014 | 67 | 67 | 66 | 67 | 99% | 100% | 63 | 6 | 10% | 9 | 14% | | Curcio 2014 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Dietrich 2014 | | 2 | 2 | 2 | 100% | 100% | 2 | 1 | 50% | 0 | 0% | | Holster 2014 | 9 | 9 | 9 | 9 | 100% | 100% | 9 | 2 | 22% | 0 | 0% | | Kratt Endoscopy 2014 | 1 | 2 | 2 | 2 | 100% | 100% | 2 | 0 | 0% | 0 | 0% | | Masci 2014 | 13 | 13 | 13 | 13 | 100% | 100% | 13 | 2 | 15% | 0 | 0% | | Selvapatt 2014 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Sulz 2014 | 15 | 15 | 14 | 15 | 93% | 100% | 14 | 2 | 14% | 0 | 0% | | Tarantino 2014 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Yau 2014 | 19 | 19 | 18 | 18 | 95% | 95% | 18 | 7 | 39% | 0 | 0% | | Zimmer 2014 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Chen Endoscopy 2015 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Granata Int J Colorectal 2015 | 4 | 5 | 5 | 5 | 100% | 100% | 5 | 1 | 20% | 0 | 0% | | Granata Endoscopy 2015 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Ivekovic 2015 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Giles 2016 | 36 | 36 | 36 | 36 | 100% | 100% | 36 | 4 | 11% | 0 | 0% | | Gubler 2016 | 5 | 7 | 7 | 7 | 100% | 100% | 7 | 2 | 29% | 0 | 0% | | Haddara 2016 | 202 | 202 | 195 | 195 | 97% | 97% | 191 | 51 | 27% | 11 | 6% | | Sinha 2016 | 20 | 20 | 19 | 19 | 95% | 95% | 19 | 3 | 16% | 0 | 0% | | Venezia 2016 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Xavier 2016 | 1 | 1 | 1 | 1 | 100% | 100% | 1 | 0 | 0% | 0 | 0% | | Total | 522 | 532 | 509 | 518 | 96% | 97% | 510 | 97 | 19% | 20 | 4% | Table 23. Summary of Clinical Literature on the use of Hemospray® Successful hemostasis defined as hemostasis achieved during procedure where Hemospray resoue, or intila followed by additional modalities. {20}------------------------------------------------ | Study | Adverse Events (n) | Upper GI | Lower GI | Lesion Types (See Table # for identifiers) | 30-day All-cause mortality (n) | 30-day GI bleeding mortality (n) | Primary Therapy (n) | Secondary Therapy (n) | |-------------------------------|--------------------------|-------------|-------------|--------------------------------------------------------------------------------|-----------------------------------------|-------------------------------------------|---------------------------|-----------------------------| | Sung 2011 | 0 | 20 | 0 | PU (20) | 0 | 0 | 20 | 0 | | Chen 2012 | 0 | 5 | 0 | Tumor (5) | 1 | 1 | 5 | 0 | | Granata 2013 | 0 | 0 | 1 | OU (1) | 0 | 0 | 0 | 1 | | Holster 2013 | 0 | 15 | 0 | PU (9), Tumor (2), Div (1), DL (1), TR (1) | 0 | 0 | 6 | 11 | | Leblanc 2013 | 0 | 12 | 0 | TR (11), post-EBS (1) | 0 | 0 | 8 | 4 | | Smith 2013 | P | 3 | 1 | PH (4) | 1 | 1 | 3 | 1 | | Smith 2013 (SEAL) | P, AP | 62 | 0 | PU (30), TR (9), Tumor (6), DL (1), Post-EBS (1), Div (1), Other (5) | 4 | 0 | 55 | 8 | | Soulellis 2013 | 0 | 0 | 4 | TR (2), DL (1), RP (1) | 0 | 0 | 0 | 4 | | Appleby 2014 | 0 | 1 | 0 | post-EBS (1) | 0 | 0 | 1 | 0 | | Chen 2014 | 0 | 50 | 17 | PU (13), OU (4), Tumor (21), DL (2), RP (1), AVM (3) | 4 | 1 | | | | Curcio 2014 | 0 | 0 | 1 | TR (…