AMNIOEXCEL® Plus vs A Marketed Comparator vs SOC in the Management of Diabetic Foot Ulcers

• ClinicalTrials.gov Identifier: NCT03547635
• Recruitment Status: Completed
• First Posted: June 6, 2018
• Results First Posted: July 20, 2020
• Last Update Posted: July 20, 2020
• Sponsor: Integra LifeSciences Corporation
• Information provided by (Responsible Party): Integra LifeSciences Corporation

Study Description

Brief Summary:

This is a multicenter, randomized, parallel-group study comparing the outcomes associated with the use of AMNIOEXCEL Plus Placental Allograft Membrane, a marketed comparator and SOC alone in the management of diabetic foot ulcers (DFUs).

Condition or disease	Intervention/treatment	Phase
Diabetic Foot Ulcer	Other: AMNIOEXCEL Plus Amniotic Membrane; Device: A Marketed Comparator; Other: Standard of Care	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a multicenter, randomized, parallel-group study comparing the outcomes associated with the use of AMNIOEXCEL Plus Placental Allograft Membrane, a marketed comparator and SOC alone in the management of diabetic foot ulcers (DFUs).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multi-Center, Randomized, Parallel-group Study Comparing AMNIOEXCEL Plus Placental Allograft Membrane to a Marketed Comparator and Standard of Care Procedures in the Management of Diabetic Foot Ulcers
• Actual Study Start Date: May 3, 2018
• Actual Primary Completion Date: February 26, 2019
• Actual Study Completion Date: February 26, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: AMNIOEXCEL Plus Amniotic Membrane	Other: AMNIOEXCEL Plus Amniotic Membrane; AMNIOEXCEL Plus is a human placental-based tissue consisting of dehydrated, tri-layer Placental (Amnion/Chorion/Amnion) Allograft Membrane (T-PAM) layers. T-PAM is a minimally manipulated placental membrane product made from tissues donated by pre-screened mothers during planned C-sections and is intended for use as a wound covering. This product is an allograft tissue intended for homologous use for the repair, reconstruction and replacement of skin at the direction of a physician. AMNIOEXCEL Plus contains Human Cellular and Tissue Based Products (HCT/P) as defined by US FDA 21 CFR Part 1271. All donor recoveries are performed by BioDlogics, LLC, and adhere to the regulations regarding HCT/P recovery and the screening and testing of the tissue donor as verified through supplier audits.
Active Comparator: A Marketed Comparator	Device: A Marketed Comparator; bi-layered skin substitute: the epidermal layer is formed by human keratinocytes and has a well-differentiated stratum corneum; the dermal layer is composed of human fibroblasts in a bovine Type I collagen lattice. It is indicated for use with standard therapeutic compression for the treatment of non-infected partial and full-thickness skin ulcers due to venous insufficiency of greater than 1-month duration and which have not adequately responded to conventional ulcer therapy. This product is also indicated for use with standard DFU care for the treatment of full-thickness neuropathic DFUs of greater than three weeks' duration which have not adequately responded to conventional ulcer therapy and which extend through the dermis but without tendon, muscle, capsule or bone exposure.; Other Name: Apligraf®
Standard of Care	Other: Standard of Care; Coban™; Conforming gauze; Optifoam® non-adhesive dressing; Cotton Gauze; Normal saline (liquid or gel); Non-adhering dressings; Steristrips; An offloading boot (Pneumatic Short Leg Walker), as appropriate

Outcome Measures

Primary Outcome Measures :

1. The Number of Participants Meeting Criteria of Complete Wound Closure, as Assessed by the Investigator at or Before Week 12 of the Treatment Phase, Which is Confirmed Closed Two Weeks Later. [ Time Frame: Wound closure assessed up to week 12 and confirmed 2 weeks later; only participants with wound closure at or before Week 12 and who maintained closure in follow-up reported ]
   Complete wound closure is defined as complete skin re-epithelialization that is without drainage or dressing requirements.

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Have participated in the informed consent process and signed a study-specific informed consent document.
2. Be able and willing to comply with study procedures, including study visits, study dressing regimens, and compliance with study required offloading device.
3. Be ≥ 21 years of age.
4. Have Type I or Type II diabetes mellitus with Investigator-confirmed glycosylated hemoglobin (HbA1c) of ≤ 12%.
5. Have at least one diabetic foot ulcer Ulcer size (i.e., area) is > 1 cm2 and < 12 cm2.
6. Have adequate vascular perfusion of the affected limb

Exclusion Criteria:

1. The subject was previously randomized and treated under this clinical study protocol.
2. The study ulcer has features that necessitates surgical operating-room debridement and/or penetrates to capsule/tendon/bone.
3. The subject is unable to safely ambulate with the use of a study required offloading boot.
4. The subject has suspected or confirmed gangrene or wound infection of the study ulcer.
5. The subject has suspected or confirmed osteomyelitis.
6. In the opinion of the Investigator, the subject has received or is scheduled to receive during study participation, a medication or treatment which is known to interfere with or affect the rate and quality of wound healing
7. The subject has a history of bone cancer or metastatic disease of the affected limb, radiation therapy to the foot, or has had chemotherapy prior to signing the Informed Consent Form for trial participation.
8. The subject is currently pregnant or is actively trying to conceive.
9. In the opinion of the Investigator, the subject is unable to comply with the treatment regimen
10. In the opinion of the Investigator, the subject has a history of, or is currently diagnosed with, any illness or condition, other than diabetes, that could interfere with wound healing.
11. In the opinion of the Investigator, the subject has a condition that could inhibit wound healing.
12. The subject has ulcers secondary to a disease other than diabetes.

Contacts and Locations

Locations

United States, California

California 1

Fresno, California, United States, 93710

California 3

Fresno, California, United States, 93710

California 2

Los Angeles, California, United States, 90063

United States, Georgia

Georgia 1

Gainesville, Georgia, United States, 30501

United States, Illinois

Illinois 1

Springfield, Illinois, United States, 62704

United States, New Jersey

New Jersey 1

Toms River, New Jersey, United States, 08753

United States, Texas

Texas 1

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Integra LifeSciences Corporation

Investigators

• Study Director: Jessica Knowlton, MS CRA; Integra LifeSciences Corporation

  Study Documents (Full-Text)

Documents provided by Integra LifeSciences Corporation:

Study Protocol  [PDF] November 5, 2018

Statistical Analysis Plan  [PDF] June 18, 2019

More Information

Publications:

Snyder RJ, Shimozaki K, Tallis A, Kerzner M, Reyzelman A, Lintzeris D, Bell D, Rutan RL, Rosenblum B. A Prospective, Randomized, Multicenter, Controlled Evaluation of the Use of Dehydrated Amniotic Membrane Allograft Compared to Standard of Care for the Closure of Chronic Diabetic Foot Ulcer. Wounds. 2016 Mar;28(3):70-7.

Martinson M, Martinson N. A comparative analysis of skin substitutes used in the management of diabetic foot ulcers. J Wound Care. 2016 Oct 1;25(Sup10):S8-S17. doi: 10.12968/jowc.2016.25.Sup10.S8.

Snyder RJ, Cardinal M, Dauphinée DM, Stavosky J. A post-hoc analysis of reduction in diabetic foot ulcer size at 4 weeks as a predictor of healing by 12 weeks. Ostomy Wound Manage. 2010 Mar 1;56(3):44-50.

• Responsible Party: Integra LifeSciences Corporation
• ClinicalTrials.gov Identifier: NCT03547635
• Other Study ID Numbers: T-AEPDFU-001
• First Posted: June 6, 2018
• Results First Posted: July 20, 2020
• Last Update Posted: July 20, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Diabetic Foot; Foot Ulcer; Ulcer; Pathologic Processes; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Foot Diseases