Study of Combined Topical Growth Factor and Protease Inhibitor in Chronic Wound Healing

Proof of Concept Study of Combined Topical Growth Factor and Protease Inhibitor in Chronic Wound Healing

Leg and foot ulcers due to venous disease or diabetes are chronic wounds that can take 6 or more months to heal. Growth factors have been used to try and improve this healing, however, many such studies have failed, and that is thought to be due enzymes in the wound that degrade the growth factors and prevent them from working. This is a proof of concept study that will evaluate the treatment of chronic leg ulcers with topically applied growth factors that are combined with a therapy to prevent their inactivation in the wound.

Study Overview

• Status: Unknown
• Conditions: Foot Ulcer, Diabetic; Venous Ulcer
• Intervention / Treatment: Biological: Becaplermin; Device: Promagran Dressing; Device: Placebo Dressing

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

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:

• Men and women aged ≥18 years
• Ulcer size 1-64 cm²
• Ulcer extends through both the epidermis and dermis, with no exposed tendon or bone
• Ulcer duration >3 months
• Ulcer located between and including the knee and ankle
• For venous leg ulcers - Venous refilling time <25s on photoplethysmography or abnormal venous insufficiency Duplex scan
• For diabetic foot ulcers - confirmed type 1 or type 2 diabetes mellitus with a haemoglobin A1C < 12%
• Wounds have not been treated with Promogran in the previous 4 weeks
• Patients able to give informed consent

Exclusion Criteria:

• Ankle-brachial index <0.8
• Ulcer with local or systemic signs of infection
• Patients who have been previously treated with Becaplermin gel
• Receiving corticosteroids or immune suppressants
• History of autoimmune disease
• Uncontrolled diabetes (baseline haemoglobin A1C > 12%)
• Severe rheumatoid arthritis
• Uncontrolled congestive heart failure
• Malnutrition (albumin <2.5g/dL)
• Unable to adhere to the protocol
• Known sensitivities to the wound dressings used in the trial
• A history of any previous malignancy
• pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Becaplermin/Promagran Dressing; Topical Becaplermin with a protease inhibitor wound dressing.	Biological: Becaplermin; 0.25 cm of 100 µg/g Becaplermin gel topically per 1cm² of ulcer area applied 3 times per week for 6 weeks.; Other Names: Regranex; Device: Promagran Dressing; 44% oxidized regenerated cellulose (ORC), 55% collagen and 1% silver-ORC wound dressing applied 3 times per week for 4 weeks.
Active Comparator: Becaplermin/Placebo Dressing; Topical Becaplermin with a placebo wound dressing.	Biological: Becaplermin; 0.25 cm of 100 µg/g Becaplermin gel topically per 1cm² of ulcer area applied 3 times per week for 6 weeks.; Other Names: Regranex; Device: Placebo Dressing; Inactive wound dressing.; Other Names: Aquacel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of Applied Growth Factors in Chronic Wound Fluid	The levels of the growth factors applied to the chronic wound will be measured using samples of the wound fluid gathered at the first two visits each week.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protease Levels in Chronic Wound Fluid	The levels of enzyme activity in the chronic wound will be measured using samples of the wound fluid gathered at the first two visits each week.	6 weeks
Chronic Wound Healing at 4 Weeks	Chronic wound healing will be measured using the VISITRAK device, which traces the outline of the chronic wound.	4 weeks
WOUNDCHEK Device Validity	The WOUNDCHEK device will be used in order to test for levels of enzyme activity in the chronic wound. This data will then be compared to the enzyme activity as determined by the levels analyzed in the chronic wound fluid.	6 weeks
Levels of Healing Biomarkers in Chronic Wound Fluid	The levels of the potential biomarker of healing GMCSF in the chronic wound fluid will be measured using samples of the chronic wound fluid collected at the first two visits each week.	6 weeks

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Michael Stacey, MBBS, Doctor of Surgery, McMaster University

Publications and helpful links

General Publications

• Stacey M. Combined Topical Growth Factor and Protease Inhibitor in Chronic Wound Healing: Protocol for a Randomized Controlled Proof-of-Concept Study. JMIR Res Protoc. 2018 Apr 27;7(4):e97. doi: 10.2196/resprot.8327.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimate): July 27, 2016

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: April 6, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Wound Healing; Protease Inhibitor; Diabetic Foot Ulcer; Venous Leg Ulcer; Growth Factor
• 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; Varicose Veins; Diabetic Foot; Foot Ulcer; Ulcer; Varicose Ulcer; Physiological Effects of Drugs; Angiogenesis Modulating Agents; Growth Substances; Anticoagulants; Angiogenesis Inducing Agents; Becaplermin
• Other Study ID Numbers: Lower Limb Ulcer Topical Ther

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes