Human Membrane Products for Foot Ulcers

(CAMPAIGN Trial)

Overseen By Brittany Bonafide

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MiMedx Group, Inc.

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

Disqualifiers: Infection, Osteomyelitis, Charcot foot, 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: Unknown

Duration: 12 weeks

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for diabetic foot ulcers that resist healing. Researchers compare special human membrane products, EPIXPRESS and EPIEFFECT, with standard care methods like cleaning and bandaging. The goal is to determine if these new products close ulcers more effectively. This trial may suit individuals with type 1 or 2 diabetes who have a foot ulcer unhealed for at least four weeks, not caused by infection. Participants must be willing to follow care instructions and attend regular study visits. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance future treatment options for diabetic foot ulcers.

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 immunosuppressants, certain chemotherapy drugs, or hydroxyurea. It's best to discuss your specific medications with the trial team.

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

Research has shown that both EPIXPRESS and EPIEFFECT, products made from the amniotic membrane, have been used to treat wounds such as diabetic foot ulcers. Derived from human placental tissue, these products are generally well-tolerated. In studies, participants reported no major side effects. EPIXPRESS and EPIEFFECT aid wound healing by acting as a protective layer. Although direct safety data for these specific products is limited, the use of placenta-based materials in wound care has shown positive results. These treatments aim to enhance healing without causing significant adverse effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care for foot ulcers, which involves cleaning, debridement, ulcer moisture balance, and offloading, EPIXPRESS and EPIEFFECT offer a novel approach using human placental tissue allografts. These treatments are unique because they include the amnion, intermediate, and chorion layers of the amniotic membrane, creating a protective barrier for wounds. EPIXPRESS is particularly exciting due to its fenestration, which aids in fluid movement and is beneficial for wounds with heavy exudate. Researchers are eager to see if these features lead to better healing outcomes for both acute and chronic wounds compared to existing methods.

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

This trial will compare the effectiveness of EPIXPRESS and EPIEFFECT, both experimental treatments, with the standard care for diabetic foot ulcers. Research has shown that materials made from the placenta, like EPIXPRESS and EPIEFFECT, heal diabetic foot ulcers more effectively than current treatments. These materials, derived from processed human placental tissue, create a protective barrier that aids in safe wound healing. This method has successfully healed ulcers completely. Both EPIXPRESS and EPIEFFECT contain layers of the amniotic membrane, which aid in wound recovery by maintaining moisture and preventing infection. Early results suggest they are promising options for individuals with non-healing diabetic foot ulcers. ^{2 3 5 6 7}

Who Is on the Research Team?

Thomas Serena, MD

Principal Investigator

SerenaGroup, Inc.

Dennis McMahon, MD

Principal Investigator

MiMedx Group, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with Type 2 Diabetes who have nonhealing diabetic foot ulcers. Participants should be seeking treatment and willing to follow the study procedures. Specific eligibility details are not provided, but typically include factors like ulcer size, duration, and overall health status.

Inclusion Criteria

I agree to follow the study's required offloading method.

I am willing and able to give my consent to participate.

If I have more than one ulcer, the largest one will be the main focus.

Exclusion Criteria

Disorder creating unacceptable risk of post-operative complications

Medical or psychological condition that may interfere with study assessments

Malnutrition indicator score less than 17 as measured on the Mini Nutritional Assessment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ppLHACM products (EPIEFFECT® or EPIXPRESS™) and Standard of Care or Standard of Care alone for nonhealing diabetic foot ulcers

12 weeks

Weekly visits for treatment and evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ppLHACM

Trial Overview The trial is testing two treatments: EPIEFFECT and EPIXPRESS—both human amnion/chorion membrane products—alongside Standard of Care (SOC), compared to SOC alone in healing diabetic foot ulcers.

How Is the Trial Designed?

Group I: EPIXPRESS Experimental Treatment 1 Intervention

EPIXPRESS™ is a PURION processed lyophilized human placental tissue allograft that includes the amnion layer, intermediate layer, and chorion layer of the amniotic membrane. The product is intended for use as a barrier to provide a protective environment in acute and chronic wounds. EPIXPRESS is fenestrated to help facilitate fluid movement and can be used on wounds that produce copious amounts of exudate.

Group II: EPIEFFECT Experimental Treatment 1 Intervention

EPIEFFECT® is a PURION processed lyophilized human placental tissue allograft that includes the amnion layer, intermediate layer, and chorion layer of the amniotic membrane. The product is intended for use as a barrier to provide a protective environment in acute and chronic wounds.

Group III: Standard of Care Active Control 1 Intervention

Standard of care will be cleaning, debridement, ulcer moisture balance, and offloading.

ppLHACM is already approved in United States for the following indications:

Approved in United States as ppLHACM for:

• Nonhealing diabetic foot ulcers

Who Is Running the Clinical Trial?

MiMedx Group, Inc.

Lead Sponsor

Trials

36

Recruited

2,800+

Founded

2008

Headquarters

Marietta, USA

Known For

Placental Biologics

Top Products

EPIFIX, EPICORD, EPIEFFECT

SerenaGroup, Inc.

Collaborator

Trials

32

Recruited

3,900+

Published Research Related to This Trial

In a case series of six patients with chronic lower leg ulcers, the use of dehydrated human amnion/chorion membrane allograft (dHACM) once a week for 5 weeks led to effective pain reduction and improved wound healing in three patients with different ulcer causes.

The study suggests that pain reduction observed after 1 to 2 applications of dHACM can predict a favorable healing response, which may help clinicians decide whether to continue or discontinue treatment, potentially reducing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain reduction by dehydrated human amnion/chorion membrane allograft in nondiabetic leg ulcers might be an early indicator of good response: A case series. Mueller, SM., Navarini, AA., Itin, P., et al.[2021]

In a study of 21 patients undergoing lower extremity surgery, the use of dehydrated human amnion and chorion allograft (dHACA) significantly improved post-treatment AOFAS scores from 35.8 to 87.5, indicating enhanced overall function and reduced pain.

The application of dHACA was associated with fewer wound complications, including no instances of wound dehiscence, suggesting it may be a beneficial adjunct in foot and ankle surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wound repair, safety, and functional outcomes in reconstructive lower extremity foot and ankle surgery using a dehydrated amnion/chorion allograft membrane. Tacktill, JZ., Rasor, Z., Adams, J., et al.[2022]

In a pilot trial involving 31 participants with diabetic foot ulcers, the addition of dried human amniotic membrane (dHAM) to standard care showed a higher healing rate (27%) compared to standard care alone (6.3%) within 12 weeks, although the difference was not statistically significant (P = .1).

The dHAM group also demonstrated a significantly greater percentage reduction in wound area (P = .0057) with no difference in adverse events between the two groups, indicating that dHAM is a safe and potentially effective treatment for diabetic foot ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of a new dried human amnion derived membrane in addition to standard care in treating diabetic foot ulcers: A patient and assessor blind, randomised controlled pilot study. Game, F., Gray, K., Davis, D., et al.[2021]

Amniotic membrane transplantation showed promising results in treating refractory chronic leg ulcers, with complete re-epithelialization achieved in one case by week 8 and an average wound size reduction of 81.93% by week 16 across four ulcers.

The treatment also significantly reduced pain intensity by 86.6% without any observed adverse effects, suggesting it is a safe and effective alternative for patients with difficult-to-treat ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amniotic membrane transplantation in the treatment of chronic lower limb ulcers. Alsina-Gibert, M., Pedregosa-Fauste, S.[2012]

In a retrospective case series of 32 patients with Achilles tendinopathy, 66% experienced complete symptom resolution within 45 days after receiving micronized dehydrated human amnion/chorion membrane (mdHACM) injections, indicating its efficacy in pain reduction.

At the first follow-up visit, 84% of patients reported improvement in pain levels, and by the second follow-up, no patients reported severe pain, demonstrating the potential of mdHACM to significantly alleviate pain associated with Achilles tendinopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Micronized Dehydrated Human Amnion/Chorion Membrane Injection in the Treatment of Chronic Achilles Tendinitis. Spector, JE., Hubbs, B., Kot, K., et al.[2022]

In a study of 11 patients with chronic diabetic foot ulcers (DFUs) who did not heal with standard care, the addition of dehydrated human amniotic membrane (dHAM) treatment led to a significant increase in healing rates, with 91% achieving complete healing by 12 weeks.

Patients treated with dHAM showed an average wound size reduction of 87.6% after 4 weeks, compared to only 26.8% with standard care alone, indicating that dHAM can greatly enhance healing outcomes for difficult-to-treat DFUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of dehydrated human amniotic membrane allografts in patients with DFUs. Zelen, CM.[2022]

The use of human amnion/chorion membrane in conjunction with standard therapy significantly improves healing rates for diabetic foot ulcers (DFUs), with a marked reduction in incomplete healing wounds compared to standard care alone, as shown in a meta-analysis of seven randomized controlled trials involving 352 initial studies.

Optimal assessment times for evaluating wound healing progress with amnion treatment are at 4 weeks and 12 weeks, indicating that early and later evaluations are crucial for understanding treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Time Sensitivity of Amniotic Membrane treatment in Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-analysis. Laurent, I., Astère, M., Wang, KR., et al.[2020]

A fresh human placental membrane allograft was successfully used to heal a chronic venous ulcer in an 89-year-old woman, demonstrating its potential effectiveness in treating long-standing wounds.

After 60 days of treatment, the ulcer was completely healed, indicating that the amniochorionic membrane can be a viable therapeutic option for chronic vascular ulcers that do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healing of a chronic ulcer of the lower limb of venous origin with fresh human amniochorionic membrane allograft Piamo, A., García, M., Romero, D., et al.[2023]

Fetal membranes, specifically amnion and chorion, can be effectively used as biological dressings for treating various types of lower extremity ulcers, as demonstrated through multiple case histories.

The authors advocate for the broader adoption of fetal membranes in clinical practice, highlighting their potential benefits in enhancing healing for pedal ulcerations encountered by podiatrists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications for the use of amnion and chorion in podiatric medicine and surgery. Boc, SF., Chairman, EL., Freed, EL.[2009]

In a study of 10 patients with category II and III pressure ulcers treated with dehydrated human amnion/chorion membrane (dHACM) allografts, 70% showed a reduction in wound size after the first application, indicating effective initial treatment.

By the end of the eight-week treatment period, 90% of the pressure ulcers had reduced in size, with three ulcers healing completely, suggesting that dHACM is a promising option for treating these types of wounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of dehydrated human amnion/chorion membrane allografts for pressure ulcer treatment: a case series. Berhane, CC., Brantley, K., Williams, S., et al.[2022]

The human acellular amniotic membrane (HAAM) was found to be effective in treating venous lower limb ulcers, with complete healing in 2 out of 4 patients and significant reductions in ulcer size and depth in all cases.

HAAM treatment not only led to improved healing outcomes, such as >50% granulation tissue formation and the disappearance of infection signs, but it also proved to be more cost-effective compared to traditional treatments like skin autografts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human acellular amniotic membrane is adopted to treat venous ulcers. Wu, Z., Liu, X., Yuan, D., et al.[2020]

Citations

1. internationaljournaloftissuerepair.com internationaljournaloftissuerepair.com/index.php/ijtr/article/view/6/10

chorion membrane and standard of care versus ... It is designed to act as a protective barrier, and is effective for both acute and chronic wounds.18 EPIXPRESS is a PURION processed placental ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06600724

Modified Platform Trial Evaluating PpLHACM and SOC ... The study will evaluate two products, EPIEFFECT® and EPIXPRESS™, which are both ppLHACMs. Official Title. A Multicenter, Prospective, Randomized Controlled ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1871402124002315

Placenta-derived biomaterials vs. standard care in chronic ... Placenta-derived biomaterials therapies have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments ...

4. mimedx.com mimedx.com/products-overview/

Products Overview | MIMEDX EPIEFFECT is a lyophilized human placental-based allograft membrane that includes the amnion layer, intermediate layer, and chorion layer. EPIEFFECT is ...

5. internationaljournaloftissuerepair.com internationaljournaloftissuerepair.com/index.php/ijtr/article/view/6/9

A multicentre, prospective, randomized controlled modified ... The present study employs a modified platform trial design to evaluate the clinical effectiveness of two PURION processed lyophilized human amnion/chorion ...

6. mimedx.com mimedx.com/epieffect/

EPIEFFECT EPIEFFECT is a lyophilized human placental-based allograft membrane that includes the amnion layer, intermediate layer, and chorion layer.

7. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=39827&ver=4&keyword=skin%20substitutes&keywordType=all&areaId=all&docType=NCA,CAL,NCD,MEDCAC,TA,MCD,6,3,5,1,F,P&contractOption=all&sortBy=relevance&bc=1

Skin Substitute Grafts/Cellular and Tissue-Based Products ... Placental Membrane Provides Improved Healing Efficacy and Lower Cost Versus a Tissue-Engineered Human Skin in the Treatment of Diabetic Foot Ulcerations.