Assessment of Wound Closure Comparing Synthetic Hybrid-Scale Fiber Matrix With Standard of Care in Treating Diabetic Foot Ulcers (DFU) and With Living Cellular Skin Substitute in Treating Venous Leg Ulcers (VLU)

In participants with diabetic foot ulcers (DFUs), this study will assess complete wound closure by comparing synthetic hybrid-scale fiber matrix (Restrata®) with standard of care.

In participants with venous leg ulcers (VLUs), this study will assess complete wound closure by comparing synthetic hybrid-scale fiber matrix (Restrata®) with living cellular skin substitute (Apligraf®)

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Foot Ulcer; Venous Leg Ulcer
• Intervention / Treatment: Device: Synthetic Hybrid-Scale Fiber Matrix; Device: Standard of Care; Device: Living Cellular Skin Substitute

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chief Science Officer; Phone Number: 844-879-2237; Email: macewan@acera-surgical.com

Study Locations

• United States
  • California
    • Vista, California, United States, 92083
      • ILD Research Center
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Jacksonville
    • Miami Beach, Florida, United States, 33169
      • Barry University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Participants with Diabetic Foot Ulcers:

1. Participant is at least 18 years old
2. Participant is willing and capable of complying with all protocol requirements
3. Participant or legally authorized representative (LAR) is willing to provide written informed consent
4. Participant has Type 1 or Type 2 diabetes (criteria for the diagnosis of diabetes mellitus per American Diabetes Association)
5. Ulcer(s) must be located at least in part on the foot or ankle
6. Ulcer(s) must be present for more than 28 days prior to randomization and initial application of study product, and has not adequately responded to conventional ulcer therapy
7. Wound size must be >1.0 cm^2 and < 25 cm^2 on the day of randomization and initial application of the study product, after initial debridement

8. Participant has adequate circulation to the affected extremity(ies), as demonstrated by at least ONE of the following within 60 days prior to enrollment/randomization:

   1. Dorsum transcutaneous oxygen test (TcPO2) of study leg(s) with results ≥40mmHg, OR
   2. Ankle-Brachial Index (ABI) of study leg(s) with results of ≥ 0.7 and ≤ 1.3, OR
   3. Toe-Brachial Index (TBI) of study extremity(ies) with results of ≥ 0.5

Exclusion Criteria for Participants with Diabetic Foot Ulcers:

1. Participant has been previously enrolled into this study, or is currently participating in another prospective drug or device study that has not reached its primary endpoint
2. Participant is pregnant, breast feeding or planning to become pregnant
3. Participant has a known allergy to resorbable suture materials, e.g. Polyglactin 910 (PGLA), Polydioxanone (PDS)
4. Participant has a life expectancy less than six months as assessed by the investigator
5. Participant has received skin substitutes during the screening period or within 14 days prior to beginning of screening period
6. Participant has an additional wound within 3 cm of the study wound(s) or study wounds are less than 3 cm apart
7. Hgb A1c > 12 percent within 3 months prior to randomization
8. Participant not in reasonable metabolic control in the judgment of the investigator
9. Participant with a known history of poor compliance with medical treatments
10. Participant currently undergoing cancer treatment
11. Participant has been diagnosed with at least one of the following autoimmune connective tissue diseases: lupus, vasculitis, sickle cell, or uncontrolled rheumatoid arthritis
12. Participant is taking parenteral corticosteroids or any cytotoxic agents for 7 consecutive days during the screening period or up to 30 days before the screening period. Chronic oral steroid use is not excluded if dose is < 10 mg per day for prednisone.
13. Active infection, undrained abscess, or critical colonization of the wound(s) with bacteria in the judgment of the investigator
14. Osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence
15. Participant unwilling or unable to safely utilize appropriate offloading device to unweight wound(s)
16. Study ulcer(s) experiences greater than 30 percent reduction over the 2-week screening period
17. Participant also has a venous leg ulcer that is enrolled into this study

Inclusion Criteria for Participants with Venous Leg Ulcers:

1. Participant is at least 18 years old
2. Participant is willing and capable of complying with all protocol requirements
3. Participant or legally authorized representative (LAR) is willing to provide written informed consent
4. Participant has peripheral venous disease per investigator judgment or diagnostic confirmation
5. Ulcer(s) must be venous in origin, located on a lower extremity
6. Ulcer(s) must be present for more than 28 days prior to randomization and initial application of study product, and has not adequately responded to conventional ulcer therapy
7. Wound(s) size must be >1.0 cm^2 and < 50 cm^2 on the day of randomization and initial application of the study product, after initial debridement

8. Participant has adequate circulation to the affected extremity(ies), as demonstrated by at least ONE of the following within 60 days prior to enrollment/randomization:

   1. Dorsum transcutaneous oxygen test (TcPO2) of study leg(s) with results ≥ 40mmHg, OR
   2. Ankle-brachial index (ABI) of study leg(s) with results of ≥ 0.7 and ≤ 1.52, OR
   3. Toe-Brachial Index (TBI) of study leg(s) with results of ≥ 0.5, OR
   4. Doppler arterial waveforms, which are triphasic or biphasic at the ankle of the affected leg(s)

Exclusion Criteria for Participants with Venous Leg Ulcers:

1. Participant has been previously enrolled into this study, or is currently participating in another prospective drug or device study that has not reached its primary endpoint
2. Participant is pregnant, breast feeding or planning to become pregnant
3. Participant has a known allergy to resorbable suture materials, e.g. Polyglactin 910 (PGLA), Polydioxanone (PDS)
4. Participant has a known allergy to bovine materials or agarose shipping materials
5. Participant has a life expectancy less than six months as assessed by the investigator
6. Participant has received skin substitutes during the screening period or within 14 days prior to the beginning of the screening period
7. Participant has an additional wound within 3 cm of the study wound or study wounds are less than 3 cm apart
8. Hgb A1c > 12 percent within 3 months prior to randomization in patients with a known history of diabetes
9. Participant is not in reasonable metabolic control in the judgment of the investigator
10. Participant has a known history of poor compliance with medical treatments
11. Participant currently undergoing cancer treatment
12. Participant has been diagnosed with at least one of the following autoimmune connective tissue diseases: lupus, vasculitis, sickle cell, or uncontrolled rheumatoid arthritis
13. Participant is taking parenteral corticosteroids or any cytotoxic agents for 7 consecutive days during the screening period or up to 30 days before the screening period. Chronic oral steroid use is not excluded if dose is < 10 mg per day for prednisone.
14. Active infection, undrained abscess, or critical colonization of the wound(s) with bacteria in the judgment of the investigator
15. Participant unwilling or unable to tolerate use of compression therapy for the duration of the study
16. Study ulcer(s) experiences greater than 30 percent reduction over the 2-week run-in period
17. Participant also has a diabetic foot ulcer that is enrolled into this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diabetic Foot Ulcer Participants Assigned to Synthetic Hybrid-Scale Fiber Matrix (Restrata®); Biweekly (every 2 weeks) application for either 12 weeks or until 100 percent epithelialization / wound closure (whichever occurs first)	Device: Synthetic Hybrid-Scale Fiber Matrix; A synthetic absorbable skin substitute indicated for use in the local management of wounds. It is made of small synthetic fibers that are designed to be similar to the structure of human skin.; Other Names: Restrata
Active Comparator: Diabetic Foot Ulcer Participants Assigned to Standard of Care; Weekly application for either 12 weeks or until 100 percent epithelialization / wound closure (whichever occurs first)	Device: Standard of Care; To ensure off-loading, each patient will be fitted with an off-loading device based on the investigator's decision, e.g. a boot for forefoot and a heel protector for hindfoot. Patients is instructed on how to care for the surgical site, utilize an off-loading device, and keep the surgical site moist and clean. If the wound is dry, a hydrogel category dressing type should be used. If the wound has exudate, an alginate or foam dressing is recommended.
Experimental: Venous Leg Ulcer Participants Assigned to Synthetic Hybrid-Scale Fiber Matrix (Restrata®); Biweekly (every 2 weeks) application for either 16 weeks or until 100 percent epithelialization / wound closure (whichever occurs first)	Device: Synthetic Hybrid-Scale Fiber Matrix; A synthetic absorbable skin substitute indicated for use in the local management of wounds. It is made of small synthetic fibers that are designed to be similar to the structure of human skin.; Other Names: Restrata
Active Comparator: Venous Leg Ulcer Participants Assigned to Living Cellular Skin Substitute (Apligraf®); Biweekly (every 2 weeks) application for either 16 weeks or until 100 percent epithelialization / wound closure (whichever occurs first)	Device: Living Cellular Skin Substitute; An absorbable skin substitute comprised of human and bovine (cow) tissues indicated for use in the local management of wounds.; Other Names: Apligraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Participants With Diabetic Foot Ulcers, number of participants with 100 Percent Epithelialization (Closure) of Wound	100 percent epithelialization of wound as assessed by a blinded evaluator via review of a three-dimensional high resolution photo of the wound plus confirmation of no drainage or need for additional dressing 2 weeks after 100 percent epithelialization	12 weeks
For Participants With Venous Leg Ulcers, number of participants with 100 Percent Epithelialization (Closure) of Wound	100 percent epithelialization of wound as assessed by a blinded evaluator via review of a three-dimensional high resolution photo of the wound plus confirmation of no drainage or need for additional dressing 2 weeks after 100 percent epithelialization	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Wound Area	Wound area measurements will be made via a three-dimensional high resolution photo of the wound with automated measurements.	Weekly assessments for 12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first.
Time to 100 Percent Epithelialization	The number of weeks from initial application of study product until 100 percent epithelialization is first identified.	12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first.
Number of Product Applications	The number of applications of study product until 100 percent epithelialization is first identified	12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on SF-36 Questionnaire Measuring Quality of Life		Day of initial product application and at either 12 weeks for DFU participants (16 weeks for VLU participants) or at 100 percent epithelialization (whichever occurs first)
Pain Reported By Participant	The pain reported by the participant on a scale of 0 through 10 with 10 being the highest level of pain the participant has experienced	Day of initial product application and at either 12 weeks for DFU participants (16 weeks for VLU participants) or at 100 percent epithelialization (whichever occurs first)
Number of Adverse Events Related to the Study Product and/or Procedure		Up to six months
Investigator's Rating of the Ease of Use and Handling of Study Product	Investigator's rating of the ease of use and handling of the study product. Investigator will rate study product as "very satisfied", "satisfied", or "not satisfied"	12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first
Cost Effectiveness	Total cost of study product applied to the participant	12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first
Number of participants with coverage of product by payor (insurance)		12 weeks for DFU participants (16 weeks for VLU participants), or until 100 percent epithelialization, whichever occurs first

Collaborators and Investigators

• Sponsor: Acera Surgical, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 9, 2021
• First Posted (Actual): June 16, 2021

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Varicose Veins; Diabetic Foot; Foot Ulcer; Ulcer; Leg Ulcer; Varicose Ulcer
• Other Study ID Numbers: 21-RES-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes