A Prospective Trial of Non-healing Diabetic Foot Ulcers Treated With Standard Care With or Without BR-AC

A Prospective, Multicenter, Randomized, Controlled Trial of Non-healing Diabetic Foot Ulcers Treated With Standard Care With or Without BR-AC

This trial is a multicenter, randomized, controlled study designed to evaluate the safety and efficacy of BioREtain® Amnion Chorion (BR-AC) plus standard of care versus standard of care only in the treatment of diabetic foot ulcers. The trial design will control potential variables that may affect the outcome between the treatment group and the control group by standardizing the requirements for debridement, wound dressings, and off-loading. Weekly subject visits will help monitor compliance in wound care and off-loading, as well as to document when wound closure is achieved. The study will also implement the use of an electronic imaging and measurement device using a standardized protocol to ensure the measuring of the wound surface area and volume is accurate, highly reproducible, and minimally variable.

There will also be a crossover treatment phase for those patients that were relegated to standard care only. After their 12-week standard of care treatment phase and for only those subjects that did not achieve complete wound closure, will be allowed to crossover for an additional 12 weeks of treatment with the BR-AC product following the protocol and procedures set forth within this document.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Other: BR-AC; Other: Standard Care

Detailed Description

This study examines a patient population with a diabetic foot ulcer (DFU) having adequate perfusion without clinical signs and symptoms of infection. Historical data has demonstrated that around 30% of DFUs heal within 12 weeks using standard care alone. However, roughly half of patients suffering from DFUs require additional measures, including advanced therapy. It is hypothesized that weekly applications of the human placental allograft BR-AC applied to a nonhealing DFU will result in a higher rate of wounds showing complete healing within 12 weeks of initiating therapy, compared to standard care alone.

This study has a crossover period, where subjects on standard care alone who do not achieve complete healing within 12 weeks of initiating therapy will be allowed to crossover to receive BR-AC over 12 additional weeks, to evaluate if their wound can achieve complete healing.

A follow-up phase will commence for all subjects that achieve complete wound closure, which is designed to measure longevity and durability of the closed wound. This follow up period will consist of a four-week follow up with two visits at each two-week interval.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • Site 02
    • Sylmar, California, United States, 91342
      • Site 04
    • Torrance, California, United States, 90502
      • Site 07
    • Vista, California, United States, 92081
      • Site 01
  • Florida
    • Miami, Florida, United States, 33175
      • Site 11
  • Illinois
    • North Chicago, Illinois, United States, 60064
      • Site 08
    • O'Fallon, Illinois, United States, 62269
      • Site 06
  • New Jersey
    • Westwood, New Jersey, United States, 07675
      • Site 10
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Site 03
    • Frisco, Texas, United States, 75034
      • Site 09
    • McAllen, Texas, United States, 78501
      • Site 05

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient has signed the informed consent form.
• Male or female patient at least 18 years of age or older, as of the date of the screening visit.
• Confirmed diagnosis of Type 1 or Type 2 Diabetes.

• Has a DFU that is located below the malleoli at least 1.0 cm2 or up to 20.0 cm2 when measured by the investigator staff at the screening visit using the Tissue Analytics device post debridement.

  a. If more than one ulcer is present the selected target ulcer must be at least 2 cm from the nearest edge of any adjacent ulcers.

• The depth of the target foot ulcer is graded as Wagner Grade I or II, i.e., with no evidence of exposed muscle, tendon, bone, or joint capsule.
• The target ulcer is "chronic, hard-to-heal," defined as having a duration of > 4 weeks but ≤ 52 weeks at the time of the screening visit.

• Arterial supply adequacy to the foot with the target ulcer confirmed by any one of the following:

  1. Great toe pressure ≥ 40 mm/Hg
  2. Systolic blood pressure Ankle Brachial Index (ABI) in the range ≥ 0.70 ≤ 1.20
  3. TcPO2 ≥ 30 mmHg from the foot
  4. Toe Brachial Index or TBI ≥ 0.50
• Willing to follow all instructions given by the Investigator, return for all visits, and adhere to off-loading protocols while on the study.

Exclusion Criteria:

• Hemoglobin A1c (HbA1c) level is > 12% (108 mmol/mol).
• Chronic oral steroid use of > 7.5 mg daily within the previous 30 days preceding screening.
• Chronic oral or parenteral corticosteroids, or any cytotoxic agents within the previous 30 days preceding screening.
• Has tested positive for Human Immunodeficiency Virus (HIV) or has Acquired Immune Deficiency Syndrome (AIDS).
• Has malignancy or history of cancer in 5 years preceding the screening visit other than non-melanoma skin cancer.
• Pregnant women.
• Women of child-bearing potential who are unwilling to avoid pregnancy or use an effective form of birth control.
• Currently on dialysis or planning to start dialysis.
• Is currently enrolled or participated in another device, drug, or biological trial within 30 days of screening.
• Has used wound treatments with enzymes, growth factors, living skin, dermal substitutes including other amniotic or umbilical cord tissue therapies, or other advanced biological therapies within the last 30 days.
• Current use of topical anti-microbial or silver-containing products.
• Target ulcer is over an active or inactive Charcot deformity.
• The depth of the target ulcer is graded as Wagner Grade III or higher, i.e., with evidence of exposed muscle, tendon, bone, and/or joint capsule.
• Gangrene is present on any part of the affected foot.
• Current suspicion of osteomyelitis, cellulitis, or other clinical signs or symptoms of target ulcer infection.
• Any previous use of Vendaje®, Vendaje AC®, AmnioWrap2® applied to the target ulcer.

The following additional exclusion criteria should be reviewed for all subjects at the end of the screening run-in period prior to randomization for eligibility determination:

• The target ulcer has decreased > 30% in wound area post debridement at baseline following the two-week run-in period.
• Use of excluded concomitant medications, therapies, or procedures during the two-week run-in period.
• Has clinical signs or symptoms of infection within the target ulcer.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BR-AC plus Standard Care; All subjects in the treatment group will receive sponsor-approved standard of care. Standard of care is defined as: Debridement,; Wound cleansing with a neutral, non-irritating and non-toxic solution,; Non-adherent wound contact layer, a foam pad, alginate or hydrofiber dressing for moderately draining wounds, a secondary retention bandage, and; An off-loading device. Using an appropriate size to cover the entire wound area, BR-AC should be applied directly to the wound surface following sharp debridement w. It is recommended that the product be trimmed to fit the area of the wound with sterile scissors before application.	Other: BR-AC; BR-AC is an amnion layer, intermediate layer, and chorion layer placental membrane processed together with no separation of the layers. BR-AC is manufactured by BioStem Technologies, Inc. and is processed by the bioREtain method which, briefly, includes initial disinfection, processing with isotonic solutions, dehydration at 37-40°C and electron beam sterilization.
Placebo Comparator: Standard Care; All subjects in the control group will receive sponsor-approved standard of care. Standard of care is defined as: Debridement,; Wound cleansing with a neutral, non-irritating and non-toxic solution,; Non-adherent wound contact layer, a foam pad, alginate or hydrofiber dressing for moderately draining wounds, a secondary retention bandage, and; An off-loading device.	Other: Standard Care; Standard of care is defined as: Debridement,; Wound cleansing with a neutral, non-irritating and non-toxic solution,; Non-adherent wound contact layer, a foam pad, alginate or hydrofiber dressing for moderately draining wounds, a secondary retention bandage, and; An off-loading device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine whether DFUs treated with standard care plus BR-AC results in a higher probability of achieving complete wound closure compared to standard care alone.	Percentage of subjects with complete wound closure over the 12-week treatment period, defined as 100% reepithelialization of the wound without drainage, where healing has been confirmed at two visits two weeks apart.	over the 12-week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare differences between treatment groups in proportions of wounds with complete wound closure, based on time in days to closure.	Time in number of days to complete wound closure over the 12-week treatment period, starting from baseline to the time of initial observation of wound closure.	over the 12-week treatment period
To compare differences between treatment groups in percent change in wound area (cm2).	Percent change from baseline in wound surface area (cm2) at 12-weeks post-randomization.	at 12 weeks
To compare differences between treatment groups in percent change in wound volume (cm3).	Percent change from baseline in wound volume (cm3) at 12-weeks post-randomization.	at 12 weeks
To determine the total number of applications of BR-AC needed to achieve complete wound closure.	Total number of applications of BR-AC to achieve complete wound closure over 12-weeks post-randomization.	over 12-weeks post-randomization
To determine whether subjects that crossover and receive standard care plus BR-AC results in a higher probability of achieving complete wound closure over the 12 additional weeks versus standard care alone.	Time from Visit 18 to initial observation of wound closure (defined as 100% reepithelialization of the wound without drainage) over an additional 12 weeks (Visits 19-30), where healing has been confirmed at two visits two weeks apart.	over an additional 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFUs that acquire clinical signs and symptoms of infections post-randomization	Differences in clinical signs and symptoms of infection from Visit 2 through end of study between the treatment groups	over 12-weeks post-randomization
Proportion of subjects experiencing adverse events, by treatment group	Spontaneously reported and elicited adverse events, coded in MedDRA	over the 17-week study period

Collaborators and Investigators

• Sponsor: BioStem Technologies
• Investigators: Study Director: Bert Slade, MD, Independent

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2024
• Primary Completion (Actual): December 5, 2025
• Study Completion (Actual): December 22, 2025

Study Registration Dates

• First Submitted: July 9, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: diabetic foot wound; non-infected diabetic foot ulcer; non-ischemic diabetic foot ulcer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Foot Ulcer; Skin and Connective Tissue Diseases; Diabetic Foot; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: BR-AC-DFU-101

Drug and device information, study documents

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