← Product Code [PGZ](/submissions/SU/subpart-e%E2%80%94surgical-devices/PGZ) · DEN130016
# XSTAT (DEN130016)
_Revmedx, Inc. · PGZ · Apr 3, 2014 · General, Plastic Surgery · DENG_
**Canonical URL:** https://fda.innolitics.com/submissions/SU/subpart-e%E2%80%94surgical-devices/PGZ/DEN130016
## Device Facts
- **Applicant:** Revmedx, Inc.
- **Product Code:** [PGZ](/submissions/SU/subpart-e%E2%80%94surgical-devices/PGZ.md)
- **Decision Date:** Apr 3, 2014
- **Decision:** DENG
- **Submission Type:** Direct
- **Regulation:** 21 CFR 878.4452
- **Device Class:** Class 2
- **Review Panel:** General, Plastic Surgery
- **Attributes:** Therapeutic
## Indications for Use
A nonabsorbable, expandable, hemostatic sponge for temporary internal use is a prescription device intended to be placed temporarily into junctional, non-compressible wounds, which are not amenable to tourniquet use, to control bleeding until surgical care is acquired. The sponges expand upon contact with blood to fill the wound cavity and provide a physical barrier and pressure that facilitates formation of a clot. The device consists of sterile, non-absorbable, radiopaque, compressed sponges and may include an applicator to facilitate delivery into a wound.
## Device Story
XSTAT is a hemostatic device for junctional wounds (groin/axilla) where tourniquets are ineffective. Device consists of syringe-style applicators containing 92 compressed, radiopaque cellulose sponges each (total 276 per device). Emergency responders deploy sponges into wound tracks; sponges expand upon contact with blood to fill cavity, provide physical pressure, and facilitate clot formation. Device is temporary (max 4 hours). Surgeons must manually remove all sponges intraoperatively using forceps and radiographic confirmation (x-pattern radiopaque filaments). Benefits include rapid hemorrhage control in austere/battlefield settings, reducing secondary effects of severe blood loss. Risks include retained material, infection, and pyrogenic response. Mitigations include specific labeling, casualty cards, and human factors training for deployment and retrieval.
## Clinical Evidence
No clinical data. Evidence based on bench testing and swine models (femoral and subclavian artery injury). Swine studies (n=10 femoral, n=8 subclavian) demonstrated rapid hemostasis (0 min mean bleeding time in femoral model) and 100% survival at 6 hours. Human factors testing (n=10) validated deployment by emergency responders (mean 50.1s) and retrieval by surgeons (n=4). Biocompatibility testing showed mild pyrogenic response; mitigated by labeling and monitoring requirements.
## Technological Characteristics
Components: compressed cellulose sponges with animal-derived coating; syringe-style plastic applicator. Radiopaque filaments in 'x' pattern for detection. Sterilization: gamma radiation (ISO 11137). Biocompatibility: ISO 10993-5, -10, -11; ASTM F756-08. Shelf life: 6 months (ASTM F1980-07). Mechanical: stress relaxation properties, expansion force/pressure. Connectivity: none.
## Regulatory Identification
A nonabsorbable expandable hemostatic sponge for temporary internal use is a prescription device intended to be placed temporarily into junctional, non-compressible wounds, which are not amenable to tourniquet use, to control bleeding until surgical care is acquired. The sponges expand upon contact with blood to fill the wound cavity and provide a physical barrier and pressure that facilitates formation of a clot. The device consists of sterile, nonabsorbable radiopaque compressed sponges and may include an applicator to facilitate delivery into a wound.
## Special Controls
In combination with the general controls of the Food, Drug & Cosmetic Act, the Non-absorbable, expandable, hemostatic sponge for temporary internal use is subject to the following special controls:
*Classification.* Class II (special controls). The special controls for this device are:(1) Performance data must demonstrate the biocompatibility of patient-contacting components.
(2) Performance data must demonstrate the sterility of patient-contacting components including endotoxin and pyrogenicity assessments.
(3) Performance data must support device stability by demonstrating continued sterility of the patient-contacting components of the device, package integrity, and device functionality over the requested shelf life.
(4) Assessment of material characteristics must be sufficient to support safety under anticipated conditions of use. Assessments must include the following:
(i) Material specifications.
(ii) Immunogenicity.
(iii) Viral inactivation for animal-derived materials.
(5) Non-clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Absorption capacity.
(ii) Extent of swelling.
(iii) Mechanical properties.
(iv) Expansion force/pressure.
(v) Radiopacity.
(vi) Deployment/applicator functionality.
(6) In vivo performance data must demonstrate safe and effective use by verifying that the device performs as intended under anticipated conditions of use. Appropriate analysis/testing must demonstrate that the product: Controls bleeding, does not promote adverse local or systemic effects, and can be completely removed from the wound. The following performance characteristics must be tested:
(i) Deployment.
(ii) Control of bleeding.
(iii) Radiopacity.
(iv) Retrieval.
(v) Assessment of local and systemic effects.
(7) Human factors testing and analysis must validate that the device design and labeling are sufficient for appropriate use by emergency responders deploying the device as well as surgeons retrieving the device from wounds.
(8) Labeling must include:
(i) Specific instructions for deployment by emergency responders and retrieval by surgeons.
(ii) Warnings, cautions, and limitations needed for safe use of the device.
(iii) Information on how the device operates and the typical course of treatment.
(iv) A detailed summary of the in vivo and human factors testing pertinent to use of the device.
(v) Appropriate imaging information to ensure complete retrieval of device.
(vi) An expiration date/shelf life.
## Submission Summary (Full Text)
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{0}------------------------------------------------
### DE NOVO CLASSIFICATION REQUEST FOR XSTAT
#### REGULATORY INFORMATION
FDA identifies this generic type of device as:
Non-absorbable, expandable, hemostatic sponge for temporary internal use: A nonabsorbable, expandable, hemostatic sponge for temporary internal use is a prescription device intended to be placed temporarily into junctional, non-compressible wounds, which are not amenable to tourniquet use, to control bleeding until surgical care is acquired. The sponges expand upon contact with blood to fill the wound cavity and provide a physical barrier and pressure that facilitates formation of a clot. The device consists of sterile, non-absorbable, radiopaque, compressed sponges and may include an applicator to facilitate delivery into a wound.
NEW REGULATION NUMBER: 21 CFR 878.4452
CLASSIFICATION: II
PRODUCT CODE: PGZ
BACKGROUND
DEVICE NAME: XSTAT
SUBMISSION NUMBER: K130218
DATE OF DE NOVO: JANUARY 28, 2013
- CONTACT: REVMEDX, INC. % John Smith, M. D., Ph. D., Regulatory consultant HOGAN LOVELLS US, LLC 555 13TH STREET NW WASHINGTON, DISTRICT OF COLUMBIA 20004
### REQUESTER'S RECOMMENDED CLASSIFICATION: II
#### INDICATIONS FOR USE
XSTAT is a hemostatic device for the control of bleeding from junctional wounds in the groin or axilla not amenable to tourniquet application in adults and adolescents.
XSTAT is a temporary device for use up to four (4) hours until surgical care is acquired. XSTAT is intended for use in the battlefield.
{1}------------------------------------------------
XSTAT is NOT indicated for use in: the thorax; the pleural cavity; the mediastinum; the abdomen; the retroperitoneal space; the sacral space above the inguinal ligament; or tissues above the clavicle.
### LIMITATIONS
The sale, distribution, and use of XSTAT are restricted to prescription use in accordance with 21 CFR 801.109.
Limitations on device use are also achieved through the following statements included in the Instructions for Use:
"For use by trained emergency responders"
"DO NOT attempt to remove sponges from wound. Sponges must be removed intraoperatively by surgeon with the capability and equipment for achieving proximal and distal vascular control."
"Assess patient for peripheral circulation and document presence of distal pulse on included casualty card. WARNING: Vascular compression greater than four hours is not recommended due to concerns related to limb ischemia."
"WARNING: Triangular segments of the applicator tip may break away from applicator during treatment. If this occurs, do not attempt to retrieve it from the wound. Record number of separated applicator tips on casualty card."
"XSTAT has not been tested for use in extremity wounds that are amenable to tourniquet application"
"XSTAT use in conjunction with tourniquet application has not been assessed for use in extremity wounds that are amenable to tourniquet application"
"Prior to wound closure, obtain plane x-ray, optimally in more than one projection. The presence of retained sponges may be easily missed on radiographic images. Thoroughly examine x-ray for radiopaque x-pattern of sponges and any triangular segments of the applicator tip that may be inadvertently retained in the wound cavity."
"If sponges or applicator tip segments are identified via x-ray, carefully re-examine wound cavity and remove them. Perform and review second x-ray to confirm complete sponge and applicator tip segment removal."
"The XSTAT elicited a mild pyrogenic response in biocompatibility tests. Monitor patient for rise in temperature, chills, hypotension, and septic shock."
"Inhibition and enhancement validation was not performed for the LAL method to confirm that the device itself does not bind and/or block detection of endotoxin."
{2}------------------------------------------------
"Contains material derived from shellfish"
## PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
### DEVICE DESCRIPTION
XSTAT consists of three sterile, syringe-style applicators containing compressed cellulose sponges with an absorbant animal-derived coating. The applicators facilitate fast delivery of the sponges into bleeding wounds. The black, telescoping handle is pulled away from the barrel of the applicator to prepare for sponge deployment. The tip of the applicator is placed into the wound track as close as possible to the source of bleeding before pushing the handle to deploy the sponges. Trained emergency responders may apply up to three applicators of sponges into junctional wounds in the groin or axilla as needed to completely pack the wound.
Each applicator houses 92 non-absorbable, expandable sponges for a total of 276 sponges per device (see Figure 1). Each sponge absorbs 3 ml of blood and a single applicator is therefore capable of absorbing approximately 300 ml. The sponges rapidly expand in length (see Figure 2) upon contact with blood or fluid to fill the wound cavity and thereby provide a physical barrier and pressure that facilitate formation of a clot. Once hemostasis is achieved, a standard occlusive dressing is applied before transporting the patient to a medical facility where surgery is performed to definitively repair the wound. The sponges are intended for temporary use up to four hours until surgical care is acquired. All sponges must be removed from wounds manually and/or with forceps by a surgeon with the capability and equipment for achieving proximal and distal vascular control. For easy detection via x-ray, one face of each tablet contains radiopaque filaments in an "x" pattern (see Figure 2). To confirm removal of all sponges and any applicator tips, a radiograph is required prior to wound closure with imaging in more than one plane recommended.
Image /page/2/Picture/5 description: The image shows three syringes filled with white tablets, a white card with red text, and a black bag with a white label. The syringes are clear with black plungers and are filled with small, white, cylindrical tablets. The white card has red text that says "XSTAT" and "ATTN TREATMENT FACILITY." The black bag has a white label that also says "XSTAT" and includes instructions for use.
Figure 1: Photograph of one device, which consists of compressed sponges housed in a syringe-style applicator. One device consists of three applicators.
Image /page/2/Picture/7 description: The image shows two white cylindrical objects next to a ruler. The ruler is labeled with both centimeters and inches. The centimeter side of the ruler goes from 1 to 7, and the inches side goes from 1 to 2. The text on the ruler says "Cat. No. 09-016".
compressed and fully expanded sponges. Radiopaque filaments are attached to one end of each sponge in an "x" pattern.
#### SUMMARY OF NONCLINICAL/BENCH STUDIES
The sponsor conducted a series of non-clinical performance testing to demonstrate that XSTAT
{3}------------------------------------------------
would perform as anticipated for its intended use population.
## BIOCOMPATIBILITY/MATERIALS
XSTAT is comprised of two main components, the XSTAT sponge and the applicator. As summarized in Table 1, these components were subjected to biocompatibility testing as recommended for a limited duration, blood contacting externally communicating device.
| Biocompatibility Test | Standard | Applicator Result | Sponge Result |
|---------------------------------------------------------|-------------------|-------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|
| Cytotoxicity (MEM Elution) | ISO 10993-5:2009 | PASS | PASS |
| Sensitization (Guinea Pig
Maximization) | ISO 10993-10:2010 | PASS | PASS |
| Irritation (Intracutaneous
Reactivity Test) | ISO 10993-10:2010 | PASS | Sponge passed testing in
non-polar solvent, but
failed in polar solvent and
thus was found to be a
moderate irritant in polar
solvent. |
| Acute Systemic Toxicity | ISO 10993-11:2006 | PASS | PASS |
| Hemocompatibility (Hemolysis
Assay - Extract Method) | ASTM F756-08 | PASS | PASS |
Table 1: Summary of Biocompatibility Tests
Material characteristics including specifications for raw materials used in the device were assessed to support safety under anticipated conditions of use. XSTAT contains a raw material derived from an animal source. For the animal derived component, manufacturing information, material specifications, and literature were provided to support the adequacy of viral inactivation and verify that the risk for immunogenicity reactions is low.
### STABILITY/STERILITY
XSTAT is labeled with a shelf life of 6 months based on testing of devices exposed to real time and accelerated aging conditions. Devices were stored on a shelf at room temperature for real-time aging with average temperature and relative humidity of 23°C and 29%. respectively (see Table 2). Devices exposed to accelerated aging conditions of 50°C for 25 days represent an equivalent of six months (ASTM F1980-07) (see Table 3). Samples were also evaluated using in vitro tests for applicator deployment force, sponge expansion rate, and package integrity (see Table 4) and met all product stability acceptance criteria.
Table 2: Real Time Aging Summary (6 months)
| Test | Criteria | Result |
|-----------------------------|-------------------------|--------|
| Applicator Deployment Force | (b)(4) Trade Secret/CCI | PASS |
| Sponge Expansion Rate | (b)(4) Trade Secret/CCI | PASS |
Table 3: Accelerated Aging Summary (25 days, equivalent to 6 months)
| Test | Criteria | Result |
|-----------------------------|-------------------------|--------|
| Applicator Deployment Force | (b)(4) Trade Secret/CCI | PASS |
| Sponge Expansion Rate | (b)(4) Trade Secret/CCI | PASS |
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#### (b)(4) Trade Secret/CCI
Table 4: Packaging Testing on XSTAT
| Test | Acceptance Criteria | Baseline Results | 6 Months Real Time Aged Results |
|-------------------------------------------|---------------------------------------------|------------------|---------------------------------|
| Bubble Emission Integrity
(ASTM F2096) | 0 fail locations. There must be no leaks. | PASS | PASS |
| Seal Peel Strength
(ASTM F88) | All seals must have seal strength ≥ 1 lb/in | PASS | PASS |
XSTAT is sterilized by gamma radiation to ensure a sterility assurance level of 10° according to ISO 11137. The device is not intended for re-sterilization or reuse. Based on the testing provided as described in Table 5, the subject device may elicit a pyrogenic response. To mitigate this risk, the labeling and training materials advise monitoring the patient for rise in temperature, chills, hypotension, and septic shock. Recommended device use is limited to no more than one device (3 total applicators of sponges) serving as a temporary wound packing for no longer than 4 hours. The risk of a possible pyrogenic response is acceptable considering the mitigations for the risk and the potential benefit of controlling bleeding that is otherwise non-compressible.
Table 5: Summary of Endotoxin and Pyrogenicity Tests
| Test | Standard | Applicator Result | Sponge Result |
|-----------------------------------------------------|---------------------|-------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Endotoxin (Limulus Amebocyte
Lysate, LAL) | USP <85>, USP <161> | PASS (< 8.50 EU/device) | Inhibition and enhancement validation was not
performed for the LAL method to confirm that
the device itself does not bind and/or block
detection of endotoxin. |
| Pyrogen (Materials Mediated
Rabbit Pyrogen Test) | USP <151> | PASS | Pyrogenic response
observed |
### PERFORMANCE TESTING - BENCH
Bench testing demonstrated that the device performs as expected under anticipated conditions of use. Testing to verify the properties and performance of the sponges included measuring the absorption capacity, extent of swelling, expansion force/pressure, mechanical properties, and radiopacity (see Tables 6 and 7). To verify ease of use and the structural integrity of the applicator, mechanical testing measured deployment forces for dry applicators as well as those immersed in liquid for 30 seconds (see Tables 8 and 9).
Table 6: Product Acceptance Criteria
| | Criteria Description | Characteristic | Acceptance Criteria |
|----------------------------|-------------------------------|-------------------------|-------------------------|
| XSTAT
Sample
Testing | Minisponge
Compression | (b)(4) Trade Secret/CCI | (b)(4) Trade Secret/CCC |
| | Minisponge
Expansion | | |
| | Functional Applicator
Test | | |
Table 7: Performance Data for Sponges
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| Test | Results |
|-------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Absorption Capacity
Extent of Swelling | (b)(4) Trade Secret/CCI |
| (b)(4) Trade Secret/CCI | |
| Mechanical Properties | Single and Multiple Sponge Force Curves: Force measured as a function of the
extent of swelling for single sponges and multiple sponges expanding in the same
direction. Within a wound, the pellets will not all expand in exactly the same
direction and there will inherently be void space between the sponges. The void
space will in essence buffer the pressure by providing some room for pellet
expansion.
Load Relaxation: The sponges exhibit stress relaxation, i.e. a time-dependent
decrease in force under constant compression. Stress relaxation will help to reduce
the pressure in a packed wound. |
| Expansion Force/Pressure | Gel Wound Simulator: Testing in a wound simulator consisting of a cavity created
in a gel indicated that pressures are different at different locations within a packed
wound. The highest pressure observed for a model wound packed with XSTAT
was 200 mm Hg, which relaxed to 150 mm Hg after 40 seconds.
Cadaver: Cadaver experiments with model junctional wounds verified that the
pressure inside a wound packed with XSTAT does not appear to be any higher
than that for a wound packed with gauze. The equilibrium pressure after packing
with XSTAT was 44 mm Hg and increased to 84 mm Hg after wrapping the
wound with an ace bandage. Moving the limbs caused changes in the volume of
the wound and therefore changes in the pressure. |
| Radiopacity (ASTM F640) | Average optical densities: background = $0.86 \pm 0.02$ , subject device = $0.70 \pm 0.01$
With 95 percent confidence (a < 0.05), the image background and subject device
OD were significantly different (P =< 0.001). |
#### Table 8: Mechanical Testing of Applicator
| Scenario-based loading condition | Criteria | Rationale for criteria | RESULTS in LBS (st dev) | | |
|--------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|--------|--------|
| | | | @ -18°C | @ 21°C | @ 43°C |
| Max force required to retract the
applicator handle in high temp, low
temp, and room temp conditions | (b)(4) Trade Secret/CCI | Ensures that the design provides an
easy one-handed engagement of the
applicator by a combat medic using a
two-finger-pull with low exertion. | Pass | Pass | Pass |
| Max force required to deploy the
applicator in high temp, low temp,
and room temp conditions. | (b)(4) Trade Secret/CCI | Ensures that the design provides an
easy one-handed deployment of the
applicator by a combat medic using
palm contact and low exertion. | Pass | Pass | Pass |
| Min force required to generate
handle failure in high temp, low
temp, and room temp conditions | (b)(4) Trade Secret/CCI | Ensures that the design provides
safe and effective performance when
engaged by a combat medic using a
one-handed, two-finger pull with high
exertion. | Pass | Pass | Pass |
| Min lateral load the applicator body
can withstand at the weakest portion
(distal end) in high temp, low temp,
and room temp conditions | (b)(4) Trade Secret/CCI | Ensures that the design provides
safe and effective performance when
exposed to lateral loading equivalent
to 2x the weight of a typical combat
medic aid bag (25 lbs). | Pass | Pass | Pass |
| Min force required to generate
failure of the locking mechanism in
high temp, low temp, and room
temp conditions. | (b)(4) Trade Secret/CCI | Ensures that the design provides
safe and effective performance when
deployed with one hand (palm
contact) by a combat medic using
high exertion. | Pass | Pass | Pass |
#### Table 9: Mechanical Testing of Applicator After Immersion in Fluid
| Test | Result |
|-----------------------------------------------------|--------|
| Deployment force after 30 sec of immersion in fluid | PASS |
## PERFORMANCE TESTING - ANIMAL
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Three animal studies using XSTAT in swine demonstrated reasonably safe and effective use by verifying that the device controls bleeding, does not promote adverse local or systemic effects, and can be completely removed the wound. Studies to assess control of bleeding from swine femoral and subclavian arteries are described in Tables 10 and 11. An additional animal subclavian artery study was submitted within a separate device master file to which the sponsor had a letter of authorization to further support device performance. The animal studies confirmed device performance characteristics including deployment, control of bleeding, radiopacity, and retrieval as well as the impact of device use on the animals in terms of local and systemic effects.
| Name of Study | GLP Evaluation of XSTAT Device in a Swine Femoral Model | |
|-----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------|
| Study Description | GLP animal study to demonstrate the performance of the XSTAT device
compared to a control article, using the United States Army Institute of
Surgical Research ("USAISR") standard femoral animal injury1,2 | |
| Number of Animals | Ten (10) animals were treated with the XSTAT device
Ten (10) animals were treated with the control article. | |
| Inclusion / Exclusion | Inclusion: Animal breed: Landrace cross swine Weight at procedure: 55 - 65 kg Age at procedure: appropriate to weight Exclusion criteria included inappropriate vessel anatomy, persistently low
MAP (<55 mmHg) prior to femoral artery injury, and significant blood
loss (>300 mL) because of surgical complication or error before femoral
artery injury. | |
| Study Procedure | All Wounds Prior to Randomization An incision was created (3.5 cm long) through the skin and subcutaneous
tissues in the groin area directly over the right femoral artery and an
approximately 3 cm section of femoral artery was exposed. The femoral artery was covered with a small piece of gauze and bathed
with 2% lidocaine HCl solution to relax the vasospasm and dilate the
artery to ≥ 5 mm outer diameter Non-traumatic vessel loops were placed proximally and distally on the
femoral artery. Using a 6.0 mm vascular punch, an arteriotomy was created. The vessel loops were released, injury start time was recorded and the
vessel was allowed to bleed freely for 45 seconds before the Test
(XSTAT) or Control Article was applied. The vessel loops were allowed to remain in the wound to facilitate
hemorrhage control during test material removal. Surgeon and device applicator were blinded to the identity of test material
prior to application. Randomization was accomplished by picking a sealed envelope that
contained the name of the test material. The contents of the envelope were
revealed in the surgery suite during the 45 second free bleed period. Wounds Randomized to XSTAT XSTAT applied as per product label immediately following the 45-second
free bleed. XSTAT applied as quickly as possible and as many as necessary until the
bleeding has stopped, or until the 5 minute limit, whichever was sooner. If room within the wound allowed, plain gauze (i.e., S-Rolled Gauze) was
packed on top of the XSTAT-filled wound | |
| Results | Cloth bandage used to secure XSTAT/Plain Gauze device within the wound. Manual compression was permitted if bleeding persisted following application of the device. Wounds Randomized to Control Article Immediately following the 45-second free bleed up to 5 minutes was allowed to apply control article(s) by packing device completely into wound track using enough control article to fill the wound and contact all bleeding surfaces. More than one device may be required. If room within the wound allowed, plain gauze (i.e., S-Rolled Gauze) was packed on top of the control article. Cloth bandage used to secure control article within the wound. Manual pressure applied for 3 minutes. Post-Randomization Care Resuscitation began 5 minutes post-injury (i.e., free bleed start time) by infusing approximately 500 ml of Hextend® fluid at a target rate of 33 mL/min through the jugular vein. Resuscitation was continued, if necessary, with pre-warmed lactated Ringer's solution (LRS) infused at a target rate of 100 mL/minute, to maintain the mean arterial pressure (MAP) to at least 65 mmHg. Following the 6-hour observation period, the Test or Control Article was removed from the wound site and the animal euthanized. XSTAT sponges were removed from the wound site manually as well as with surgical forceps. Control article(s) were pulled out of the wound manually. Following sponge removal and euthanasia, the wound site was imaged using a portable fluoroscopy unit. No sponges were identified in the fluoroscopic images or at necropsy. | |
| | Endpoints | XSTAT |
| | 1: Bleeding Time, mean: Duration of bleeding (visible blood shed from the wound site) occurring at any time immediately following test material application until exsanguination or end of the 6 hour observation period. | 0 Minutes |
| | 2: Post-Treatment Blood Loss, mean (stdev): Amount of blood shed from the wound cavity during the time period following the 45 second free bleed until exsanguination or end of the 6 hour observation period. | 21.7 (17.5) mL |
Table 10: Swine Femoral Artery Study
{7}------------------------------------------------
{8}------------------------------------------------
| | Pressure (MAP), mean | | | |
|----------------|---------------------------------------------------------------------------------------------------------------------------------------|-------------------|---------------------------------------------------------------------------------|--|
| | (stdev): Mean arterial | | | |
| | pressure recorded just | | | |
| | prior to exsanguination | | | |
| | or end of the 6 hour | | | |
| | observation period. | | | |
| | 4: Survival Time, | | | |
| | mean (stdev): Time | | | |
| | period immediately | | | |
| | following the 45 | | | |
| | second free bleed | | | |
| | during which vital | | | |
| | signs are; MAP | 6.0 (0.0) hours | 6.0 (0.0) hours | |
| | >20mmHg and PCO2 | | | |
| | >15 mmHg to | | | |
| | exsanguination or end | | | |
| | of the 6 hour | | | |
| | observation period. | | | |
| | 5: Percentage | | | |
| | Survival: Percentage of | | | |
| | animals surviving to | | | |
| | the end of the study | | | |
| | observation period (6 | 100% | 100% | |
| | hours) for a given | | | |
| | treatment, where | | | |
| | survival was defined as | | | |
| | the MAP >20 mmHg | | | |
| | and PCO2 >15 mmHg. | | | |
| | 6: Wound Packing | | | |
| | Time, mean (stdev) | 1.1 (0.3) minutes | 4.6 (0.5) minutes | |
| | 7: Wound | | | |
| | Compression Time | 0 minutes | 3 minutes | |
| | | | | |
| | | | The presence or absence of distal limb ischemia was not assessed in this study. | |
| | There was no postmortem evidence of blood tracking beneath the skin. | | | |
| | Mean XSTAT removal time 10.5 ± 3.4 minutes. | | | |
| | | | | |
| Device Removal | Mean control article removal time 2 ± 0.8 minutes.
Neither test nor control article material adhered to the wound or were found to | | | |
| | | | | |
| | be retained in the wound at necropsy. | | | |
'Kheirabadi BS, Arnaud F, McCarron R et al. Development of a Standard Swine Hemorrhage Model for Efficacy Assessment of Topical Hemostatic Agents. J of Trauma. 2011;71:S139-S146. "Littlejohn LF, Devlin JJ, Kircher SS, et al. Comparison of Celox-A, ChitoFlex, WoundStat, and Combat Gauze Hemostatic Agents Versus Standard Gauze Dressing in Control of Hemorrhage in a Swine Model of Penetrating Trauma. Acad Emerg Med. 2011;18:340-350. Acheson, E.M., et al. Comparison of Hemorrhage Control Agents Applied to Lethal Extremity Arterial Hemorrhages in Swine. J of Trauma. 2005;59:865-875.
| Table 11: Swine Subclavian Artery Study | | | | | | |
|-----------------------------------------|--|--|--|--|--|--|
|-----------------------------------------|--|--|--|--|--|--|
| Name of Study | Evaluation of XSTAT Device in a Swine Subclavian Model |
|-----------------------|----------------------------------------------------------------------------------------------|
| Study Description | Animal study to demonstrate the performance of the XSTAT device in a swine subclavian injury |
| Number of Animals | 8 |
| Inclusion / Exclusion | Inclusion: Animal breed: Landrace cross swine |
{9}------------------------------------------------
| | Weight at procedure: 55 - 65 kg Age at procedure: appropriate to weight | |
|-----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------|
| | Exclusion criteria included inappropriate vessel anatomy, persistently low
MAP (<65 mmHg) prior to femoral artery injury. | |
| | Animal anesthetized and 4.5-cm incision was created to access the subclavian artery and vein Subclavian artery and vein transected After 30-second free bleeding, the wound cavity was filled with the XSTAT sponges with no external pressure. Resuscitative fluids were administered to the animal as needed to support a mean arterial blood pressure of 60 mmHg. No additional wound care was provided during the 1-hour observation period. Following the 1-hour observation period, the XSTAT sponges were removed from the wound site and the animal euthanized. | |
| Study Procedure | | |
| | Endpoint | XSTAT |
| | 1: Animals with hemostasis at 4 min after device application. | 7 / 8 (87.5%) |
| | 2: Animals with hemostasis at 60 min after device application | 7 / 8 (87.5%) |
| | 3: Animal Survival at 60 min where survival was defined as the MAP > 20 mmHg and PCO2 > 15 mmHg. | 8 / 8 (100%) |
| | 4: Bleeding Time, mean (StDev) Duration of bleeding occurring at any time immediately following material application until study termination | 7.9 (21.1) |
| Results | 5: Post-TBL, mean (stdev) Amount of blood shed from the wound cavity during the time following the 45 second free bleed until study termination | 331.5 (818.9) |
| | The failure to achieve hemostasis in one of the animals was due to an applicator tip breaking off and falling into the wound. The location of the tip in the wound created a small gap (1 cm) that prevented sponges from accessing the point of bleeding. As a result, applicator tips are now secured with glue | |
## PERFORMANCE TESTING – HUMAN FACTORS
Human factors testing and analysis validated that the device design and labeling are sufficient for appropriate use by emergency responders deploying the device as well as surgeons retrieving the device from wounds (see Tables 12 and 13). Human factors assessments were used to modify the labeling to promote reasonably safe and effective use of XSTAT.
Table 12: Device Deployment Human Factors Study
| Name of Study | User Evaluation of XSTAT Device and Applicator Use |
|--------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Study Description | A user evaluation (human factors) was completed to determine the ability of
medics and civilian EMS to understand and execute instructions for using
XSTAT and applying XSTAT on a simulated casualty. |
| Number of subjects | 10 |
{10}------------------------------------------------
| Inclusion / Exclusion | Military medic or civilian EMS with no prior knowledge or experience of
using XSTAT device prior to the study | | | |
|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|------------------------------------------|----------------------------------------------------------------------------------|
| Study Procedure | A medical-mannequin torso served as a wound model. The wound track—located in the upper thigh region approximately 5 cm distal to the iliac artery—had a diameter of 3 cm and a length of 8 cm and was pre-filled with 150-200 mL of saline. Participants were tested in a low-light environment. Participants were evaluated on the time needed to ready the device for use, as well as the time necessary to deploy the appropriate amount of material to stop bleeding. All participants passed the device usage criteria which involved opening the package, cocking the applicator, applying the applicator into the wound, applying the correct number of applicators, and deploying XSTAT in under 90 seconds (mean (stdev): 50.1(12.6) sec.). The study did not assess a user's ability to properly diagnose a severely bleeding junctional wound in the groin or axilla not amenable to tourniquet application. | | | |
| Results | Participant | Time (sec) | User Comments | Actions Taken |
| | 1 | 45 | | |
| | 2 | 31 | Add detail on pulling/locking applicator | Revised instruction on pulling/cocking application handle |
| | 3 | 47 | Add detail on preclinical data | Added detailed information on preclinical testing to product insert |
| | 4 | 70 | | |
| | 5 | 43 | Explain importance of direct pressure | Added detailed instructions regarding application of direct pressure and bandage |
| | 6 | 71 | | |
| | 7 | 53 | | |
| | 8 | 47 | | |
| | 9 | 54 | Add detail on pulling/locking applicator | Revised instruction on pulling/cocking application handle. |
| Table 13: Sponge Retrieval Human Factors Study | | |
|------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| Name of Study / Cited
Publication | User evaluation of XSTAT device removal | |
| Study Description | A user evaluation was completed to assess the ability of surgeons to
understand and execute instructions for removing XSTAT sponges from
human cadaver wounds. | |
| Number | 4 surgeons; 1 cadaver; 2 wounds, 2 tests/wound. | |
| Inclusion / Exclusion | Inclusion: civilian or military surgeon with no prior experience with XSTAT
prior to the study. | |
| Study Procedure | Junctional wounds were made in each shoulder of the cadaver.
●
Saline solution was circulated through cadaver's vasculature to simulate
●
blood flow.
Following application of 2 XSTAT devices into the shoulder wounds.
● | |
{11}------------------------------------------------
| | each surgeon was handed draft instructions for use and instructed to treat
the wound. | |
|---------------------------------------------------------------------|------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------|
| | Endpoint | Result |
| Endpoints/Results | 1. Labeling clear on use of XSTAT device (Yes / No) | 4 of 4 surgeons indicated 'Yes' |
| | 2. Completed all steps in IFU without assistance (Yes / No) | 4 of 4 surgeons completed |
| | 3. IFU conveys necessity of removal of sponges, median* | 4.5 |
| | 4. IFU conveys steps to assure removal, median* | 4.5 |
| | 5. Effective order of removal steps, median* | 4.5 |
| | 6. Ease of removal of sponges, median* | 3.5 |
| | * Scale: 1…
---
**Source:** [https://fda.innolitics.com/submissions/SU/subpart-e%E2%80%94surgical-devices/PGZ/DEN130016](https://fda.innolitics.com/submissions/SU/subpart-e%E2%80%94surgical-devices/PGZ/DEN130016)
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