Multiple Treatments for Foot and Leg Ulcers

Recruiting at 14 trial locations

Overseen By Karen Bartku

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Integra LifeSciences Corporation

Must not be taking: Immunosuppressants, Hydroxyurea, Biologics, others

Disqualifiers: Pregnancy, End stage renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different treatments for foot and leg ulcers compared to standard care. It tests special products made from animal or human tissue, such as AmnioExcel Plus (a placental allograft membrane) and the Urinary Bladder Matrix (UBM) sheet device, alongside usual treatments like cleaning and dressing the ulcers. People with diabetic foot ulcers or hard-to-heal venous leg ulcers may be suitable candidates, especially if their ulcers have not healed for some time and are not too large. Participants must attend weekly study visits and follow treatment instructions. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could enhance healing outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications like immunosuppressants, high doses of corticosteroids, cytotoxic chemotherapy, or hydroxyurea. It's best to discuss your current medications with the trial team to see if they might interfere with the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the Urinary Bladder Matrix (UBM) sheet device is generally well-tolerated. Made from pig bladder tissue, this scaffold has been used in wound care. Studies have shown it helps heal diabetic foot ulcers and venous leg ulcers without major safety issues for most patients.

For AmnioExcel Plus, a product made from human placental tissue, evidence also suggests it is safe for treating chronic wounds like diabetic foot ulcers. Previous studies reported its use as a protective barrier with no significant adverse events.

Both treatments have been researched in settings similar to this trial, demonstrating their safety for use in humans with wounds. While each treatment may have some risks, studies so far have found them to be minor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they introduce new ways to tackle foot and leg ulcers. The Urinary Bladder Matrix (UBM) sheet device, derived from porcine extracellular matrix, offers a unique scaffold that may promote faster healing by supporting tissue regeneration. On the other hand, AmnioExcel Plus utilizes a tri-layered human placental membrane, which could enhance healing by providing essential growth factors and proteins directly to the ulcer site. Both treatments, combined with the standard care of cleaning, debridement, and moisture balance, aim to improve outcomes more effectively than traditional methods alone.

What evidence suggests that this trial's treatments could be effective for foot and leg ulcers?

Research has shown that the Urinary Bladder Matrix (UBM) sheet device, a treatment in this trial, aids in healing wounds such as diabetic foot and venous ulcers. It helps rebuild tissue and can improve healing rates compared to regular treatments. The UBM provides a structure that supports the body's natural repair process.

AmnioExcel Plus, another treatment option in this trial, is made from human placental membrane and shows promise in healing wounds like diabetic foot ulcers. It does not cause an immune reaction and has properties that reduce inflammation, aiding in wound healing. Studies have reported positive results compared to standard treatments, with better healing rates. ^{1 2 3 6 7}

Who Is on the Research Team?

Tomas Serena, MD

Principal Investigator

SerenaGroup, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with type 1 or 2 diabetes who have had a foot or leg ulcer for 4-52 weeks. The ulcer must be full thickness, not expose bone, and measure between 1.0 cm² and 25.0 cm² post-debridement. Participants need good blood flow in the limb and must agree to offload the affected area and attend weekly visits. Exclusions include severe uncontrolled diabetes (HbA1c ≥12%), recent use of certain medications, malnutrition, pregnancy, other clinical trials within the last month, or conditions affecting wound healing.

Inclusion Criteria

My ulcer has been present for 4 to 52 weeks before my first screening visit.

My foot ulcer is mostly located below my ankle.

My ulcer is deep but does not show any exposed bone.

Exclusion Criteria

I am taking medication that affects my immune system or wound healing.

Medical or psychological condition interfering with study assessments

Known life expectancy of < 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive weekly treatment with CAMPs or Standard of Care until ulcer closure or a maximum of 12 weeks

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• AmnioExcel Plus
• Standard of Care
• Urinary Bladder Matrix (UBM) sheet device

Trial Overview The study compares different treatments for diabetic foot and venous leg ulcers: Standard of Care alone versus Standard of Care plus either Urinary Bladder Matrix (UBM) sheet device or AmnioExcel Plus. It aims to see which method best achieves complete closure of these chronic wounds.

How Is the Trial Designed?

Group I: Venous Leg Ulcers with a Urinary Bladder Matrix (UBM) sheet device Experimental Treatment 2 Interventions

Participants will receive treatment with Urinary Bladder Matrix (UBM) sheet device, a porcine-derived extracellular matrix scaffold, and weekly treatment with standard of care (cleaning, debridement, ulcer moisture balance, and offloading) until ulcer closure, or a maximum of 12 weeks, whichever occurs first.

Group II: Venous Leg Ulcers with AmnioExcel Plus Experimental Treatment 2 Interventions

Participants will receive treatment with AmnioExcel Plus, a tri-layer (amnion-chorion-amnion) dehydrated human placental membrane allograft, and weekly treatment with standard of care (cleaning, debridement, ulcer moisture balance, and offloading) until ulcer closure, or a maximum of 12 weeks, whichever occurs first.

Group III: Diabetic Foot Ulcers with Urinary Bladder Matrix (UBM) sheet device Experimental Treatment 2 Interventions

Participants will receive treatment with Urinary Bladder Matrix (UBM) sheet device, a porcine-derived extracellular matrix scaffold, and weekly treatment with standard of care (cleaning, debridement, ulcer moisture balance, and offloading) until ulcer closure, or a maximum of 12 weeks, whichever occurs first.

Group IV: Diabetic Foot Ulcers with AmnioExcel Plus Experimental Treatment 2 Interventions

Participants will receive treatment with AmnioExcel Plus, a tri-layer (amnion-chorion-amnion) dehydrated human placental membrane allograft, and weekly treatment with standard of care (cleaning, debridement, ulcer moisture balance, and offloading) until ulcer closure, or a maximum of 12 weeks, whichever occurs first.

Group V: Standard of Care Active Control 1 Intervention

Beginning at the screening visit, participants will receive weekly treatment with standard of care (cleaning, debridement, ulcer moisture balance, and offloading) until ulcer closure, or a maximum of 12 weeks, whichever occurs first.

Who Is Running the Clinical Trial?

Integra LifeSciences Corporation

Lead Sponsor

Trials

110

Recruited

11,300+

Mojdeh Poul

Integra LifeSciences Corporation

Chief Executive Officer

Bachelor’s and Master’s degrees in Mechanical Engineering from the University of Louisville, MBA from the University of North Carolina at Chapel Hill

Dr. Lisa Egbuonu-Davis

Integra LifeSciences Corporation

Chief Medical Officer since 2023

MD from Harvard Medical School

SerenaGroup, Inc.

Collaborator

Trials

32

Recruited

3,900+

Published Research Related to This Trial

Primary care providers play a crucial role in the initial treatment of chronic leg ulcers, which can significantly influence healing and limb preservation.

The paper reviews fundamental wound healing principles and management strategies for the three most common types of leg ulcers—venous stasis, ischemic, and diabetic foot ulcers—highlighting the need for evidence-based approaches in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leg ulcers: a practical approach to the leg ulcer patient. Ennis, WJ., Meneses, P.[2004]

Lower extremity ulcers, including venous, arterial, and neurotropic types, require comprehensive care that addresses the underlying causes, promotes moist healing, and focuses on pain management to improve quality of life.

If an ulcer does not show signs of healing within 6 to 12 weeks, it is crucial to biopsy the wound to confirm the diagnosis and develop an appropriate treatment plan, which may include the use of biological therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An approach to leg and foot ulcers: a brief overview. Sibbald, RG.[2005]

This paper is the first in a two-part series that reviews both clinical studies and economic models related to treatments for diabetic foot ulcers, focusing specifically on standard topical therapies.

The findings aim to provide a comprehensive understanding of the efficacy and cost-effectiveness of these treatments, setting the stage for the second part that will cover advanced treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical therapies for diabetic foot ulcers: standard treatments. White, R., McIntosh, C.[2016]

Effective treatment of leg ulcers involves removing dead tissue and using local antiseptics to prevent infection, highlighting the importance of proper wound care.

The selection of local dressings should consider factors like the amount of dead tissue, fluid drainage, overall cost, and how well the patient can adhere to the treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Local treatment of leg ulcers]. Hubert, A., Gheeraert, P.[2019]

In a study involving 102 community nurses and 145 patients in Oslo, Norway, it was found that a significant portion of patients (34%) had not received a formal diagnosis for their leg ulcers, highlighting a gap in care.

Saline was the most commonly used cleansing solution, and while compression therapy was applied to all ulcer types, over half of the patients experienced pain, with 9% not receiving any pain relief, indicating a need for better pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the leg and foot ulcer treatment provided in Oslo. Haram, RB., Ribu, E., Rustøen, T.[2019]

A systematic review of 144 randomized controlled trials on treatments for venous leg ulcers revealed inadequate reporting of external validity data, which is crucial for understanding how findings apply to broader patient populations.

Only 32% of studies reported eligibility screening numbers, and there was significant variability in the ankle-brachial pressure index cutoff for patient inclusion, complicating the generalizability of the results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External validity of randomized controlled trials of interventions in venous leg ulceration: A systematic review. Gethin, G., Ivory, JD., Connell, L., et al.[2020]

A foot care education program did not significantly reduce the incidence of foot ulcers or amputations in patients with newly healed foot ulcers over 12 months, as both the intervention and control groups had similar ulcer rates (41%).

While the education improved protective foot care behaviors among participants, it did not lead to significant improvements in mood or quality of life, indicating that further evaluation of educational strategies for high-risk patients is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Education for secondary prevention of foot ulcers in people with diabetes: a randomised controlled trial. Lincoln, NB., Radford, KA., Game, FL., et al.[2022]

The pilot study for the Canadian Bandaging Trial (CBT) demonstrated that the study protocol for comparing compression bandages in treating venous leg ulcers (VLUs) was practical and efficient, involving 12 participants and 40 nurses over 6 months.

Challenges were identified in patient recruitment, with only 12 out of 49 screened patients enrolled, indicating a need for adjustments in eligibility criteria and additional clinical sites to enhance future research effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Community leg ulcer bandaging study: lessons learned in a pilot, randomized controlled trial . Smith, LJ., Harrison, MB., Graham, ID., et al.[2010]

In a Swedish study, medical staff were uncertain about the cause of chronic leg ulcers in 40% of cases, highlighting the need for accurate aetiological diagnosis to tailor effective treatments.

An interdisciplinary approach to treatment, which includes causal therapy, wound care, and addressing quality of life factors like pain and nutrition, can significantly improve outcomes for patients with chronic leg ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Venous leg ulcer. Management, care , quality of life]. Lindholm, C.[2006]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05024656

AmnioExcel® Plus vs SOC in the Management of Diabetic ... This is a prospective, multicenter, randomized, parallel-group Trial comparing the outcomes associated with the use of AmnioExcel® Plus Placental Allograft ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/35/NCT03547635/Prot_000.pdf

Integra LifeSciences Title: A Prospective, Multi-Center, Randomized, Parallel-group Study Comparing. AMNIOEXCEL Plus Placental Allograft Membrane to Apligraf Bi-layered Skin.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4828514/

Dehydrated Amniotic Membrane Allograft for Treatment of ... Human amniotic CTPs are non-immunogenic and have anti-inflammatory effects, with beneficial properties in wound healing related to the release of growth factors ...

4. ocfasa.com ocfasa.com/clinical_studies/a-prospective-multi-center-randomized-parallel-group-study-comparing-amnioexcel-plus-placental-allograft-membrane-to-apligraf-bi-layered-skin-substitute-and-standard-of-care-procedures-in-the-manag/

A Prospective, Multi-Center, Randomized, Parallel-Group ... ... Amnioexcel Plus Placental Allograft Membrane to Apligraf Bi-Layered Skin Substitute and Standard of Care Procedures in the Management of Diabetic Foot Ulcers.

5. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=35041

LCD - Skin Substitute Grafts/Cellular and Tissue-Based ... This LCD covers skin substitute grafts/cellular and tissue-based products (CTP) for the treatment of diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) in ...

6. products.integralife.com products.integralife.com/amnioexcel-plus-placental-allograft-membrane/product/wound-reconstruction-care-outpatient-clinic-private-office-treat-amnioexcel-plus-placental-allograft-membrane

AmnioExcel® Plus Placental Allograft Membrane AmnioExcel® Plus Membrane is intended for use as a wound covering. This product is an allograft tissue intended for homologous use as a protective barrier ...

7. uhcprovider.com uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/skin-soft-tissue-substitutes.pdf

Skin and Soft Tissue Substitutes Patients with chronic wounds, such as diabetic foot ulcers, pressure ulcers, and venous leg ulcers, experience loss of function, pain, wound ...