Assessment of the Safety and Efficacy of DERMASTREAM™ - ENZYSTREAM™ System for the Treatment of Chronic Venous Ulcers

Study Overview
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Brief Summary
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The study objectives are to evaluate DermastreamTM - EnzystreamTM system safety, tolerability and efficacy, as a potent method for debridement of nonhealing lower extremity chronic venous ulcers patients.

Detailed Description
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This is a phase I/II prospective, randomized, double blind, placebo controlled, dose escalating, three patient-group study, to evaluate the safety and efficacy of DermaStream™ - EnzyStream™ System in non-healing lower extremity chronic venous ulcers patients. The DermaStream™ - EnzyStream™ System will be evaluated during continues streaming of 3 different doses of EnzystreamTM (papain based) solution given in an escalating order (15,000, 30,000 and 60,000 papain USP units/ml) up to 5 consecutive treatment days. Each treatment session lasts for 6 hours. This study is a Multi center trial. It is anticipated that three (3) sites will enroll subjects into this study. Overall, forty eight (48) patients will be recruited, and randomly allocated to placebo or EnzyStream™ treatment in each study dose group prior to EnzyStream™ administration. The ratio of drug to placebo treated patients will be 4;1, namely 12 patients will be administered with EnzyStream™ solution and 4 patients will be placebo treated in each of the three respective EnzyStream™ dose groups. Treatment will start with the lowest dose (15,000 papain USP units/ml) administered over a 6 hour period followed with saline wash for an additional half an hour. The treatment dose will be increased to the next highest dose, for the next patients group only following safety analysis, and the procedure will be repeated. The treatment period will be followed by a 3 month follow up period. During the follow up period patients will be observed for every 2 weeks during the first month and once a month (every 20 days) during the 2 additional months (allowing a time window of ± 3 days).

Official Title
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A Phase I/II Randomized, Double Blind, Placebo-Controlled Dose- Escalating Study, to Assess The Safety and Efficacy of Enzystream™ Debriding Solution (Papain) Applied by Dermastream™ Device for the Treatment of Lower Extremity Chronic Venous Ulcers

Conditions
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Lower Extremity Chronic Venous Ulcers

Intervention / Treatment
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* Other: Papain
* Other: Papain
* Other: Papain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have a venous leg ulcer Participants, either men or women are between 18 and 85 years of age. Clinical presentation of venous insufficiency demonstrated by Doppler Ankle-Brachial Index > 0.7 by Doppler Good palpable pulses in the Posterior Tibial and the Dorsalis Pedis arteries. Wound present for at least 6 weeks prior to enrolment. Wound length is in the range of: 1.5 - 7 centimeters. The necrotic tissue area is at least 20% of wound area. (by clinical evaluation, i.e., inspection). Wound San Antonio classification: Grade 1 or 2, Stage A or B. Wound location: foot or calf, at a location where the device can be attached properly. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure. Women of child bearing potential must use adequate birth-control precautions. Exclusion Criteria: Documented sensitivity to Papain, by medical history records. Patients in need of surgical debridement. Patients with general skin disorders (Psoriasis, Peniculitis ect) that might deteriorate as a result of local trauma. Patients with skin disorders unrelated to the ulcer that are presented adjacent to the wound. Pain sensation is completely absent (wound area is anesthetic). Patients with renal failure. (Cr > 2 mg/dl). Patients with impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit value). Patients having Hypoalbuminemia: (Albumin < 2gr/dl ). Patients with general Immunological disorders that might deteriorate as a result of local trauma. Right-side congestive heart failure (CHF) with edema of legs: (NYHA class 2 or higher see APPENDIX 5). Participation in another clinical trial within 1 month prior to start of this study. Subject unwilling or unable to comply with the requirements of the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose papain<br>Ratio of drug to placebo treated patients will be 4:1 | Other: Papain<br>* 15,000 USP U/ml<br>|
| Experimental: Medium dose papain<br>Ratio of drug to placebo treated patients will be 4:1 | Other: Papain<br>* 30,000 USP U/ml<br>|
| Experimental: High dose papain<br>Ratio of drug to placebo treated patients will be 4:1 | Other: Papain<br>* 60,000 USP U/ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate Dermastream-Enzystream safety | Skin irritation score | Up to 88 days | 
| To demonstrate Dermastream-Enzystream safety | Severity and incidence of adverse events | Up to 88 days | 
| To demonstrate Dermastream-Enzystream safety | No deterioration in clinical laboratory parameters | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| •Assessment of changes in wound debridement status during treatment period | Change in non viable tissue area | Days 1-5 | 
| Assessment of wound closure | Reduction of nonviable tissue area | Up to 88 days | 
| Assessment of wound closure | Increase of granulation tissue area | Up to 88 days | 
| Assessment of wound closure | Time (in days) for wound closure | Up to 88 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Wounds, Venous Ulcers, Papain, Debridement, Continuous streaming, DermaStream-EnzyStream