Dressing with product derived from snake venom to treat wounds in the legs

Phase 1

• Conditions: Venous ulcer

• Registration Number: RBR-9j7qqr
• Lead Sponsor: Faculdade de Medicina de Botucatu - Unesp

Brief Summary

Background: The heterologous fibrin sealant (HFS) consists of a fibrinogen-rich cryoprecipitate extracted from Bubalus bubalis buffaloes blood and a thrombin-like enzyme purified from Crotalus durissus terrificus snake venom. This study aimed to evaluate safety and immunogenicity, confirm the lowest dose used, and to assess the preliminary efficacy of the of HFS to treat chronic venous ulcers (CVU). Methods: A phase I/II non-randomized, single-arm clinical trial was performed on 31 participants, accounting for a total of 69 active CVU. All ulcers were treated with the HFS, essential fatty acid, and Unna boot for twelve weeks. The outcomes assessed were: (1) primary - safety, immunogenicity analyses, and confirmation of the lowest safe dose; (2) secondary - preliminary efficacy by analyzing the healing process. Immunogenicity was evaluated by serum-neutralizing (IgM and IgG) and -non-neutralizing (IgA and IgE) antibody technique against the product. Immuno-detection of IgE class antibodies was also assessed by dot-blot assay before and at the end of treatment. Positive samples on dot-blot assays were subsequently submitted to Western blot assays to confirm the results. Results: No severe systemic adverse event related to use of HFS was observed. Local adverse events possibly related to the product were ulcer pain (52%), peri-ulcer maceration (16%), peri-ulcer pruritus (12%), critical colonization (8%), peri-ulcer eczema (4%), the opening of new ulcers (4%),, and increased ulcerated area 4%). Neutralizing and non-neutralizing antibodies did not show significant deviations at none of the evaluated moments. Blot assays have shown all patients had presented negative immunological reaction, either before or after the treatment to the thrombin-like enzyme component of HFS. Also, two participants showed a positive immunological reaction to the cryoprecipitate component and two were positive before and remained so during the treatment. To secondary outcomes of preliminary efficacy, there was total healing in 47.5% of the ulcers, a significant reduction of the area in 22% of them, and a qualitative improvement in wound beds of unhealed ulcers. Conclusions: The investigational HFS product proved to be safe and non-immunogenic, with good preliminary efficacy for the treatment of CVU according to the proposed protocol and doses. A phase III clinical trial will be necessary to prove these findings.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-29
• Results First Posted: 2020-12-21
• Last Update Posted: 29 May 2023

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: Not specified
• Target Recruitment: Not specified

Inclusion Criteria

Sign the term of free and informed consent; patients 18 years of age or older, of both sexes; chronic venous disease with chronic venous ulcers evidenced by one or more of the following signs: hyperpigmentation of the distal third of the lower limb, stasis eczema, lipodermatosclerosis, varicose veins; to have at least one ulcer whose time evolution is minimum of 6 weeks and a maximum of 5 years; display the sum of the areas of the ulcers of both members between 5 and 60 square centimeters; at least one ulcer whose major area is above 5 square centimeters; do not use the following drugs in the last two weeks prior to screening: venotonics, pentoxifylline, fibrinolytic drugs; Available to attend once a week for treatment.

Exclusion Criteria

Leg ulcers of other etiologies ( causes hematological , neoplastic , infectious , among others) ; use of anticoagulants ; infected ulcers , or associated with erysipelas , cellulitis or lymphangitis; ulcer with critical colonization , ie ,large amount of exudate and / or foul and / or yellowish staining of the wound bed and / or green and / or red opaque odor and / or friable granulation tissue ; necrosis in the ulcer bed ; devitalized background with ulcer covering all your bed; venous ulcers associated with peripheral arterial disease that is characterized when the systolic ankle-brachial index is less than 0.9 and / or absence of distal pulses; being unable or does not wish to remain with compressive treatment of lower limb for seven days; to have a history of allergy to treatment with Unna boot; to have a history of allergy to treatment with essential fatty acid; known or suspected pregnancy;
values coagulation outside the normal range ( Activated partial thromboplastin time more than 1.25 and time and prothrombin activity less than 70% or more than 100%); women of childbearing potential not using contraception.

Study & Design

• Study Type: Intervention
• Study Design: Not specified