Use of dHACM in the Treatment of Venous Leg Ulcers

A Randomized Controlled Clinical Trial Evaluating The Application Of Dehydrated Human Amnion/ Chorion Membrane (dHACM) Plus Standard Of Care Vs. Standard Of Care Alone In The Treatment Of Venous Leg Ulcers

The overall objective of this study is to evaluate the effectiveness of dehydrated human amnion/ chorion membrane (dHACM) in reducing time to complete wound closure in patients with venous leg ulcers (VLUs).

Study Overview

• Status: Completed
• Conditions: Leg Ulcer
• Intervention / Treatment: Procedure: Multi-layer compression therapy; Other: Application of dHACM

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Associated Foot & Ankle Specialists, PC
  • California
    • Carlsbad, California, United States, 92009
      • ILD Research
    • Castro Valley, California, United States, 94546
      • Center for Clinical Research, Inc.
    • Fair Oaks, California, United States, 95628
      • Center for Clinical Research, Inc.
    • Fresno, California, United States, 93720
      • Limb Preservation Platform, Inc.
    • Loma Linda, California, United States, 92357
      • VA Loma Linda Healthcare System
    • Mather, California, United States, 95655
      • VA Northern California
    • San Francisco, California, United States, 94115
      • Center for Clinical Research, Inc.
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Veteran's Administration
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • VA Western New York Health Care System
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Center for Clinical Research, Inc.
  • Pennsylvania
    • Haverford, Pennsylvania, United States, 19041
      • SGM Physicians
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny-Singer Research Institute
  • South Carolina
    • Columbia, South Carolina, United States, 29209
      • William Jennings Bryan Dorn Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Index ulcer characteristics:

   1. Full-thickness venous leg ulcer for ≥ 30 days
   2. Ulcer area after debridement is ≥ 1 cm² and ≤ 25 cm² at the randomization visit
   3. Has a clean, granulating base with minimal adherent slough
2. Subject has completed 14 day run-in period with ≤ 25% wound area reduction post-debridement.

3. Have one of the following:

   • Ankle Brachial Pressure Index (ABI) > 0.75. (Calculations will be made using measurements from both posterior tibial and dorsalis pedis arteries as well as both arms) OR
   • Have venous insufficiency confirmed by duplex ultrasound examination for valvular or venous incompetence.
4. Age ≥ 18.
5. Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence).
6. Ability to read/understand and sign Informed Consent and Release of Medical Information Forms.
7. Ability to understand and comply with weekly visits and follow-up regimen.

Exclusion Criteria:

1. Index Ulcer Assessment - Index ulcer meeting the following criteria will not be eligible for enrollment:

   1. Penetrates down to muscle, tendon, or bone
   2. Presence of another venous ulcer ≤ 2 cm from index ulcer
   3. Is deemed by the Investigator to be caused by a medical condition other than venous insufficiency
   4. Exhibits clinical signs and symptoms of infection
   5. If in the opinion of the Investigator, the wound is suspicious for cancer, the subject should undergo an ulcer biopsy to rule out carcinoma. If carcinoma is ruled out, the subject may be re-screened.
   6. Located on the dorsum of the foot or with more than 50% of the ulcer below the malleolus

2. Prior therapies - Subjects receiving treatment with any of the following will not be eligible for enrollment:

   1. In the last 7 days - Negative pressure wound therapy of the index ulcer
   2. In the last 7 days - Hyperbaric oxygen therapy
   3. In the last 30 days - Treatment with cytotoxic chemotherapy, application of topical steroids to the ulcer surface, or use of ≥ 14 days of immune-suppressants (including systemic corticosteroids); or, subject is anticipated to require such medications during the course of the study
   4. In the last 30 days - study ulcer treatment with any advanced therapy, including EpiFix®, tissue engineered materials (e.g. Apligraf® or Dermagraft®), or other scaffold materials (e.g. OASIS® Wound Matrix, MatriStem® Wound Matrix)
   5. In the last 30 days - Subject has been on any investigational drug(s) or therapeutic device(s)
   6. In the last 8 weeks - Amputation or revascularization (surgical or stenting) to the affected leg
   7. Any history of radiation at the ulcer site
   8. Any prior participation in a MiMedx® study
   9. Study ulcer has undergone ≥ 12 months of continuous high strength compression therapy over its duration

3. Subject criteria that will make subject ineligible for enrollment:

   1. Known osteomyelitis or active cellulitis at wound site
   2. Hemoglobin A1C >12 in the last 60 days prior to randomization
   3. Active malignant disease or subject is less than 1 year disease-free
   4. NYHA Class III and IV congestive heart failure (CHF), as defined by the following criteria: Class III: Symptoms with moderate exertion; Class IV: Symptoms at rest
   5. Auto-immune disorders including Systemic Lupus Erythematosus (SLE), Fibromyalgia, Acquired Immunodeficiency Syndrome (AIDS) or HIV
   6. Allergy or known sensitivity to Aminoglycosides such as gentamicin sulfate and/or streptomycin sulfate
   7. Known allergy to the components of the multi-layer compression bandaging, or who cannot tolerate MLCT
   8. Presence of any condition (including current drug or alcohol abuse, medical or psychiatric condition) that is likely to impair understanding of or compliance with the study protocol in the judgment of the Investigator
   9. Pregnancy at enrollment or within last 6 months, women who are breastfeeding, or women of childbearing potential who are planning to become pregnant during the time of the study OR are unwilling/unable to use acceptable methods of contraception (birth control pills, barriers, or abstinence)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dHACM; Application of multi-layer compression therapy with application of dHACM.	Procedure: Multi-layer compression therapy; Application of multi-layer compression therapy.; Other: Application of dHACM; Application of dHACM to ulcer.
Other: Control; Application of multi-layer compression therapy without application of dHACM.	Procedure: Multi-layer compression therapy; Application of multi-layer compression therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to 100% epithelialization of study ulcer	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients in both groups with complete wound healing at 12 weeks	12 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Comparison of Quality of Life as assessed by Short Form 36 (SF-36)	16 weeks
Crossover Subject Analysis	12 weeks

Collaborators and Investigators

• Sponsor: MiMedx Group, Inc.
• Investigators: Study Director: Don Fetterolf, MD, MiMedx Group, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): August 5, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (Estimate): December 13, 2013

Study Record Updates

• Last Update Posted (Actual): August 24, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer
• Other Study ID Numbers: EFVLU003