VA MERIT: A Comparative Efficacy Study: Treatment of Non-Healing Diabetic (DOLCE)

A Comparative Efficacy Study: Treatments of Non-Healing Diabetic Foot Ulcers

The primary objective of this study is to assess the effectiveness of cellular dermal replacement tissue vs. non-viable extracellular matrix (ECM) for the treatment of non-healing diabetic foot ulcers. Our hypothesis is that these devices are of equal efficacy.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Device: SECONDARY dressing gauze and tape; Procedure: debridement, irrigation; Device: Dermagraft; Device: Oasis

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95655
      • VA Northern California Health Care System, Mather, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

(Answering NO will exclude patient):

• An Institutional Review Board (IRB) Informed Consent Form signed and dated prior to any study-related activities.
• The area of the study ulcer after debridement is between 1 cm2 and 25 cm2 at Visit 3/Week 0.
• Subjects between 18 and 85 years of age.
• Subject's highest Ankle-Brachial Pressure Index (ABPI) / Ankle-Arm Index (AAI) is greater than or equal to 0.80 and lower than 1.4 (the highest ABPI/AAI value from three measurements within last 6 months shall apply).or a toe-arm index is equal to or higher than 0.6.
• The patient has one or more diabetic ulcers on the target foot with only one ulcer selected as the study (target) ulcer. The target ulcer must be at least 4 cm from a non-target ulcer and in the Investigator's opinion, be unlikely to coalesce with another ulcer within 12 weeks of randomization.
• Subject's study ulcer is full thickness and does not extend to bone, muscle, or tendon.
• Subject's study ulcer has been present at least 4 weeks prior to the initial screening (Visit 1) or 6 weeks at randomization (Visit 3).
• Subject has been diagnosed with Type 1 or Type 2 diabetes and HbA1c is less than 10%.
• Study ulcer has no clinical feature of infection (2 signs of inflammation and elevated bacterial load of the wound).
• For female subjects of childbearing age potential, the subject has a negative pregnancy test and is not lactating for the duration of the study.
• Subject understands the requirements of this study and is willing to comply with all the study requirements.

Exclusion Criteria:

(Answering YES will exclude patient):

• The subject is diagnosed with cancer and is undergoing treatment with immunosuppressive or chemotherapeutic agents, radiotherapy or systemic corticosteroids less than 30 days before enrollment.
• The subject is diagnosed with HIV/AIDS.
• The subject is diagnosed with any bleeding disorders.
• The subject is diagnosed with any connective tissue diseases.
• For female subjects, the subject is pregnant or lactating.
• The subject has a history of illicit drug use within one year of enrollment.
• In the past year, the subject experiences episodes of drinking more than 5 alcoholic beverages in less than two hours and/or drinking alcohol has become a problem in interpersonal relationships, work, driving and/or their behavior in general.
• The subject has any active infected wounds or osteomyelitis (confirmed by bone biopsy, MRI or bone scan).
• Doppler exam within the last 365 days demonstrating reflux greater than 0.5 seconds.
• The subject is diagnosed with active Charcot as described by Saunder's classification system.
• The subject manifests signs of poor nutritional status and/or albumin level < 2.9.
• The subject has been exposed to Dermagraft and/or Oasis in the last 60 days.
• The study ulcer size is less than 0.5 cm2 or greater than 25 cm2.
• The subject has any porcine allergy or cow product allergy.
• The subject's recent (last 30 days) chemistry tests serum creatinine is 2 times above the upper limit of normal and/or LFT's 3 times above the upper limit of normal.
• Between Visit 1/Week -2 and Visit 3/Week 0 (randomization) the study ulcer has decreased in size by more than 40%, or increased in size by more than 50%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard of care; debridement, irrigation , PRIMARY dressing Adaptic and Iodosorb, SECONDARY dressing gauze and tape	Device: SECONDARY dressing gauze and tape; SECONDARY dressing gauze and tape; Procedure: debridement, irrigation; debridement, irrigation
EXPERIMENTAL: Dermagraft; debridement, irrigation , PRIMARY dressing Dermagraft and Adaptic, SECONDARY dressing gauze and tape	Device: SECONDARY dressing gauze and tape; SECONDARY dressing gauze and tape; Procedure: debridement, irrigation; debridement, irrigation; Device: Dermagraft; Dermagraft per company protocol
EXPERIMENTAL: Oasis; debridement, irrigation , PRIMARY dressing Oasis and Adaptic, SECONDARY dressing gauze and tape	Device: SECONDARY dressing gauze and tape; SECONDARY dressing gauze and tape; Procedure: debridement, irrigation; debridement, irrigation; Device: Oasis; Oasis per company protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Closure by Week 15	The primary outcome of interest is defined as the wound healed completely on or before visit 15, regardless of a later recurrence.	15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound Closure at 20 Weeks	Complete wound closure at study endpoint. The Secondary outcome of interest is defined as the wound healed completely on or before visit 19, regardless of a later recurrence. The number of subjects analyzed at secondary outcome differs from primary outcome due to some subjects not completing the study.	20 weeks
Cost Effectiveness		12 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: VA Northern California Health Care System
• Investigators: Principal Investigator: Rivkah R. Isseroff, MD, VA Northern California Health Care System, Mather, CA

Publications and helpful links

General Publications

• Lev-Tov H, Li CS, Dahle S, Isseroff RR. Cellular versus acellular matrix devices in treatment of diabetic foot ulcers: study protocol for a comparative efficacy randomized controlled trial. Trials. 2013 Jan 9;14:8. doi: 10.1186/1745-6215-14-8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2011
• Primary Completion (ACTUAL): December 14, 2017
• Study Completion (ACTUAL): April 4, 2018

Study Registration Dates

• First Submitted: October 7, 2011
• First Submitted That Met QC Criteria: October 12, 2011
• First Posted (ESTIMATE): October 13, 2011

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2019
• Last Update Submitted That Met QC Criteria: August 26, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Diabetic Foot Ulcer; Oasis; Chronic wounds; Chronic ulcers; Dermagraft; Adaptic
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: SURG-005-10S; 11-04-00618 (OTHER_GRANT: VA Northern California Health Care System)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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.: Yes