Assessment of the Safety and Efficacy of DERMASTREAM™ - ENZYSTREAM™ System for the Treatment of Chronic Venous Ulcers (ENZ-DER-002-IL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00485329
Recruitment Status : Completed
First Posted : June 12, 2007
Last Update Posted : May 25, 2010
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lower Extremity Chronic Venous Ulcers Other: Papain Phase 1 Phase 2

Detailed Description:

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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: 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
Study Start Date : July 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Arm Intervention/treatment
Experimental: Low dose papain
Ratio of drug to placebo treated patients will be 4:1
Other: Papain
15,000 USP U/ml
Experimental: Medium dose papain
Ratio of drug to placebo treated patients will be 4:1
Other: Papain
30,000 USP U/ml
Experimental: High dose papain
Ratio of drug to placebo treated patients will be 4:1
Other: Papain
60,000 USP U/ml

Primary Outcome Measures :
  1. To demonstrate Dermastream-Enzystream safety [ Time Frame: Up to 88 days ]
    Skin irritation score

  2. To demonstrate Dermastream-Enzystream safety [ Time Frame: Up to 88 days ]
    Severity and incidence of adverse events

  3. To demonstrate Dermastream-Enzystream safety [ Time Frame: 5 days ]
    No deterioration in clinical laboratory parameters

Secondary Outcome Measures :
  1. •Assessment of changes in wound debridement status during treatment period [ Time Frame: Days 1-5 ]
    Change in non viable tissue area

  2. Assessment of wound closure [ Time Frame: Up to 88 days ]
    Reduction of nonviable tissue area

  3. Assessment of wound closure [ Time Frame: Up to 88 days ]
    Increase of granulation tissue area

  4. Assessment of wound closure [ Time Frame: Up to 88 days ]
    Time (in days) for wound closure

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patient must have a venous leg ulcer
  2. Participants, either men or women are between 18 and 85 years of age.
  3. Clinical presentation of venous insufficiency demonstrated by Doppler
  4. Ankle-Brachial Index > 0.7 by Doppler
  5. Good palpable pulses in the Posterior Tibial and the Dorsalis Pedis arteries.
  6. Wound present for at least 6 weeks prior to enrolment.
  7. Wound length is in the range of: 1.5 - 7 centimeters.
  8. The necrotic tissue area is at least 20% of wound area. (by clinical evaluation, i.e., inspection).
  9. Wound San Antonio classification: Grade 1 or 2, Stage A or B.
  10. Wound location: foot or calf, at a location where the device can be attached properly.
  11. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.
  12. Women of child bearing potential must use adequate birth-control precautions.

Exclusion Criteria:

  1. Documented sensitivity to Papain, by medical history records.
  2. Patients in need of surgical debridement.
  3. Patients with general skin disorders (Psoriasis, Peniculitis ect) that might deteriorate as a result of local trauma.
  4. Patients with skin disorders unrelated to the ulcer that are presented adjacent to the wound.
  5. Pain sensation is completely absent (wound area is anesthetic).
  6. Patients with renal failure. (Cr > 2 mg/dl).
  7. Patients with impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit value).
  8. Patients having Hypoalbuminemia: (Albumin < 2gr/dl ).
  9. Patients with general Immunological disorders that might deteriorate as a result of local trauma.
  10. Right-side congestive heart failure (CHF) with edema of legs: (NYHA class 2 or higher see APPENDIX 5).
  11. Participation in another clinical trial within 1 month prior to start of this study.
  12. Subject unwilling or unable to comply with the requirements of the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00485329

Hillel Yafe Medical Center
Hadera, Israel, 38101
Rambam Medical Center
Haifa, Israel, 35254
Assaf Harofe Medical Center
Zriffin, Israel
Sponsors and Collaborators
Principal Investigator: Arie Bass, Prof. Assaf Harofe Medical Center
Principal Investigator: Sami Nitezki, Dr. Rambam Health Care Campus

Additional Information: Identifier: NCT00485329     History of Changes
Other Study ID Numbers: ENZ-DER-002-IL
First Posted: June 12, 2007    Key Record Dates
Last Update Posted: May 25, 2010
Last Verified: May 2010

Keywords provided by EnzySurge:
Chronic Wounds, Venous Ulcers, Papain, Debridement, Continuous streaming

Additional relevant MeSH terms:
Varicose Ulcer
Pathologic Processes
Varicose Veins
Vascular Diseases
Cardiovascular Diseases
Leg Ulcer
Skin Ulcer
Skin Diseases