Clinical trial NCT06565156: Non-healing Diabetic Foot Ulcers Treated With Standard Care With or Without BR-AM
Official title: A Prospective, Multicenter, Randomized, Controlled Trial of Non-healing Diabetic Foot Ulcers Treated With Standard Care With or Without BR-AM
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-infected Diabetic Foot Ulcer
Diabetic Foot
Diabetic Wound
Diabetic Foot Ulcer
Non-ischemic Diabetic Foot Ulcer
Lead sponsor: BioStem Technologies
Sponsor class: INDUSTRY
First posted: 2024-08-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is a multicenter, randomized, controlled study designed to evaluate the safety and efficacy of BioREtain® Amniotic Membrane (BR-AM) 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 offloading. 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-AM product following the protocol and procedures set forth within this document.

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-AM 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.

Eligibility criteria: 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 eKare 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.

Primary outcomes:
measure: To determine whether DFUs treated with standard care plus BR-AM results in a higher probability of achieving complete wound closure compared to standard care alone.
timeFrame: over the 12-week treatment period
Secondary outcomes:
measure: To compare differences between treatment groups in proportions of wounds with complete wound closure, based on time in days to closure.
timeFrame: at 12 weeks
measure: To compare differences between treatment groups in percent change in wound area (cm2).
timeFrame: at 12 weeks
measure: To compare differences between treatment groups in percent change in wound volume (cm3).
timeFrame: at 12 weeks
measure: To determine the total number of applications of BR-AM needed to achieve complete wound closure.
timeFrame: over 12-weeks post-randomization
measure: To determine whether subjects that crossover and receive standard care plus BR-AM results in a higher probability of achieving complete wound closure over the 12 additional weeks versus standard care alone based on time in days to closure.
timeFrame: over an additional 12 weeks
Other outcomes:
measure: Number of participants that acquire clinical signs and symptoms of infections post-randomization
timeFrame: over 12-weeks post-randomization
measure: Proportion of subjects experiencing adverse events, by treatment group
timeFrame: over the 17-week study period
Locations:
city: Guntersville
country: United States
facility: Site 17
state: Alabama
city: Mesa
country: United States
facility: Site 22
state: Arizona
city: Tucson
country: United States
facility: Site 25
state: Arizona
city: Palmdale
country: United States
facility: Site 19
state: California
city: Coral Gables
country: United States
facility: Site 27
state: Florida
city: Deerfield Beach
country: United States
facility: Site 20
state: Florida
city: DeLand
country: United States
facility: Site 28
state: Florida
city: Springfield
country: United States
facility: Site 23
state: Illinois
city: Boston
country: United States
facility: Site 18
state: Massachusetts
city: Detroit
country: United States
facility: Site 26
state: Michigan
city: Lake Success
country: United States
facility: Site 16
state: New York
city: Chapel Hill
country: United States
facility: Site 15
state: North Carolina
city: Brownsville
country: United States
facility: Site 29
state: Texas
city: Burleson
country: United States
facility: Site 21
state: Texas
city: San Antonio
country: United States
facility: Site 24
state: Texas
Study officials:
affiliation: Independent
name: Bert Slade, MD
role: STUDY_DIRECTOR
References: