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A Study to Evaluate the Efficacy and Safety of NexoBrid in Subjects With Thermal Burns

Phase 3
Completed
Conditions
Thermal Burns
Interventions
Drug: Gel Vehicle
Procedure: Standard of Care (SOC)
Registration Number
NCT02148705
Lead Sponsor
MediWound Ltd
Brief Summary

This study will be a three-arms study intending to demonstrate superiority of NexoBrid treatment over the Gel Vehicle placebo control treatment and over SOC in thermal burn subjects.

The study objectives are:

1. To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing complete eschar removal as compared with Gel vehicle,

2. To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing earlier complete eschar removal, reduction in patients' surgical burden and its related blood loss as compared to SOC,

3. To assess the safety of NexoBrid compared to SOC, including demonstration that treatment with NexoBrid does not cause an unacceptable level of harm on wound closure outcome and long term outcomes of cosmesis and function.

Detailed Description

This is a multi-center, multi-national, randomized, controlled, assessor blinded, three-arm study aiming to demonstrate superiority of NexoBrid treatment over Gel Vehicle control and over SOC treatment in thermal burn subjects with burns. Following the enrollment of a patient to the study and prior to randomization Physicians will define one or more Target Wounds (TWs) per subject according to TWs definition. All subjects' deep (DPT and FT) burns that comply with the specified entrance criteria are intended to receive study treatment per the randomized study arm.

The randomization procedure will be initiated only after all Target wounds of a subject have been defined. Patients will be assigned to the treatment arm in a 3:3:1 ratio (NexoBrid: SOC : Gel Vehicle).

Patients will be treated in the same way in all study arms (NexoBrid, SOC or Gel vehicle) except for the eschar removal stage which will be performed as per the randomization study arm.

Prior to initiation of eschar removal treatment, subjects will be medicated with appropriate analgesia and undergo wound cleansing and dressing of all wounds with antibacterial solutions . Following wound cleansing and antibacterial treatments, subjects will undergo the eschar removal process as per treatment assignment (NexoBrid, SOC or Gel Vehicle, following randomization).

Subsequent to complete eschar removal, all wounds will be assessed and treated in the same manner, in accordance with post-eschar removal wound care strategy. Post eschar removal, subjects will undergo daily vital signs and pain assessments, until hospital discharge (HD) and weekly assessments of wound progress, until wound closure. Following wound closure confirmation visit, subjects will be followed up at 1, 3, 6, 12, 18 and 24 months post wound closure for long term outcomes evaluation.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
175
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Gel VehicleGel VehicleGel Vehicle is applied to the burn wound at a dose of 20 g sterile Gel per 1% of TBSA (\~ surface of an adult palm) for four hours.
NexoBrid GelNexoBridNexoBrid Gel is applied to the burn wound at a dose of 2 g NexoBrid sterile powder mixed with 20g sterile Gel Vehicle per 1% of TBSA (\~ surface of an adult palm) for four hours.
Standard of Care (SOC)Standard of Care (SOC)Subjects in the SOC group may be treated with a combination of surgical and non-surgical eschar removal procedures, according to the investigator's judgment.
Primary Outcome Measures
NameTimeMethod
Primary Endpoint: Number of Participants With Complete Eschar Removal.post application (post 2 h soaking)

Comparison of NexoBrid over Gel Vehicle for eschar removal as measured by Number of Participants with complete eschar removal at the end of the topical agent soaking period by a blinded assessor.

Secondary Outcome Measures
NameTimeMethod
Secondary Endpoint: Patient-Level Comparison of Actual Blood Loss (Volume in mL) Related to Eschar Removal for NexoBrid vs SOC (FAS)For NexoBrid arm, blood loss during NexoBrid application until post soaking. For SOC arm, blood loss during SOC procedures, through last dressing change for non-surgical SOC arm and through excision surgery for surgical SOC arm.

Comparison of NexoBrid over SOC with regard to the blood loss (volume in mL) occurred during the eschar removal procedures.

Secondary Endpoint: Number of Participants With Surgical Excision Performed or Eschar Removal for NexoBrid vs SOC (FAS)Post application (post 2 h soaking) for NexoBrid arm and immediately post surgical excision for SOC arm.

Comparison of NexoBrid over SOC in number of Participants with surgical need for excisional eschar removal as measured by an analysis of incidence of surgical eschar removal (tangential/ minor/ avulsion/ Versajet and/or dermabrasion excision).

Secondary Endpoint: Comparison of Time (Days) to Complete Eschar RemovalFrom randomization until complete eschar removal. For NexoBrid, assessed post application (post 2 h soaking) and for SOC assessed immediately post last dressing change for non-surgical SOC arm and immediately post excision for surgical SOC arm.

Comparison of NexoBrid over SOC with regard to the time (in days) when complete eschar removal has been achieved. Results of the Generalized Wilcoxon-Gehan Test Adjusted for Overall TW Depths, TBSA Group, Center Group, and Number of TWs (FAS)

Trial Locations

Locations (29)

University of Texas Medical Branch

🇺🇸

Galveston, Texas, United States

The General Hospital Corporation d/b/a Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

HarborView Medical Center

🇺🇸

Seattle, Washington, United States

University of South Alabama Department of Surgery

🇺🇸

Mobile, Alabama, United States

Medstar Washington Hospital Center

🇺🇸

Washington, District of Columbia, United States

Joseph M. Still Research Foundation, Inc.

🇺🇸

Augusta, Georgia, United States

Johns Hopkins Bayview Medical Center

🇺🇸

Baltimore, Maryland, United States

Klinika popálenin a rekonstrukční chirurgie, Fakultní nemocnice Brno

🇨🇿

Brno, Czechia

Emergency Medicine Stony Brook University Hospital

🇺🇸

Stony Brook, New York, United States

Rambam Medical Center

🇮🇱

Haifa, Israel

Spitalul Clinic de Urgenta de Chirurgie Plastica, Reparatorie si Arsuri

🇷🇴

Bucharest, Romania

New-York Presbyterian Hospital

🇺🇸

New York, New York, United States

Spitalul Clinic de Urgenta "Sf. Ioan"

🇷🇴

Bucharest, Romania

Ospedale di Cisanello

🇮🇹

Pisa, Italy

Unfallkrankenhaus Berlin Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie

🇩🇪

Berlin, Germany

Khechinashvili University Hospital - Thermal Injuries

🇬🇪

Tbilisi, Georgia

The University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

BG Universitätsklinikum Bergmannsheil GmbH

🇩🇪

Bochum, Germany

Spitalul Clinic de Urgenta "Bagdasar-Arseni"

🇷🇴

Bucharest, Romania

Regional Medical Center ,Regional One Health

🇺🇸

Memphis, Tennessee, United States

Burnett Burn Center at The University of Kansas Hospital

🇺🇸

Kansas City, Kansas, United States

Maricopa Medical Center

🇺🇸

Phoenix, Arizona, United States

University of Utah Hospital

🇺🇸

Salt Lake City, Utah, United States

Columbia St. Mary's, Inc.

🇺🇸

Milwaukee, Wisconsin, United States

University of Colorado at Denver, Teaching

🇺🇸

Aurora, Colorado, United States

University of Florida- Dept. of Surgery

🇺🇸

Gainesville, Florida, United States

University Hospital, Department of Plastic Surgery

🇧🇪

Gent, Belgium

Lehigh Valley Hospital and Health Network

🇺🇸

Allentown, Pennsylvania, United States

Hospital A. Cardarelli of Napoli

🇮🇹

Napoli, Italy

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