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

NCT02148705 | Completed Phase 3 Results DMC

• 1 other identifier: MW 2010-03-02
• Study Type: interventional
• Target: 175
• Locations: 8 countries
• Sites: 29

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. 1.To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing complete eschar removal as compared with Gel vehicle,
2. 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. 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.

Conditions

Thermal Burns

Keywords

fire/flame; scalds; contact

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: Number of Participants With Complete Eschar Removal.

  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.

  post application (post 2 h soaking)

Secondary Outcomes (3)

• 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.

• Secondary Endpoint: Comparison of Time (Days) to Complete Eschar Removal

  From 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.

• 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.

Study Arms (3)

NexoBrid Gel

EXPERIMENTAL

NexoBrid 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.

Drug: NexoBrid

Gel Vehicle

PLACEBO COMPARATOR

Gel 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.

Drug: Gel Vehicle

Standard of Care (SOC)

ACTIVE COMPARATOR

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.

Procedure: Standard of Care (SOC)

Interventions

NexoBrid DRUG

NexoBrid Gel

Standard of Care (SOC) PROCEDURE

Standard of Care (SOC)

Gel Vehicle DRUG

Gel Vehicle

Eligibility Criteria

• Age: 18 Years - 77 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females; ≥ 18
• Thermal burns caused by fire/flame, scalds or contact,
• Patient total burns area ≥ 3% DPT and / or FT,
• Patient total burns area should be ≤ 30% TBSA; SPT, DPT and/or FT in depth,
• Informed consent can be obtained within 84 hours of the burn injury,
• Patients who are willing and able to sign a written consent form.
• At least one wound (a continuous burn area) that is ≥0.5% TBSA (DPT and/or FT) (this minimal wound size should not including face, perineal or genital area.
• All planned target wounds (TWs) should meet the following criteria:
• SPT area that cannot be demarcated from DPT and FT areas should be less than 50% of the % TBSA of the TW.
• Wound's blisters can be removed/ unroofed, as judged by the investigator.

You may not qualify if:

• Patients who are unable to follow study procedures and follow up period.
• Modified Baux index ≥ 80,
• Patients with burned charred fingers, 3rd degree in depth and possibly devoid of circulation,
• Patients with abraded wound/s that cannot be treated by an enzymatic debrider application (NexoBrid) will be excluded from the study,
• Patients with electrical or chemical burns,
• Patients with circumferential (≥ 80% of the limb circumference) DPT and/or FT burns defined as Extremities at Risk (EAR) 2 as described in the protocol.
• The following pre-enrollment dressings: a. Flammacerium, b. Silver Nitrate (AgNO3),
• Patients with pre-enrolment wounds which are covered by eschar heavily saturated with iodine or by SSD pseudoeschar (e.g. pseudoeschar as a result of \> 12 hours SSD treatment),
• Patients with pre-enrollment escharotomy.
• Patients with diagnosed infections as described in Section 11.9 of study protocol,
• Diagnosis of smoke inhalation injury.
• Pregnant women (positive pregnancy test) or nursing mothers.
• Poorly controlled diabetes mellitus (HbA1c\>11%) in patients with known diabetes as captured in the medical history.
• BMI greater than 39.0 kg/m2 in patients with burn area up to 15% TBSA or BMI greater than 34.0 kg/m2 in patients with burn area more than 15% TBSA.
• ASA greater than 2 (Appendix 13- ASA classification system)

Sponsors & Collaborators

• MediWound Ltd: lead

Study Sites (29)

University of South Alabama Department of Surgery

Mobile, Alabama, 36617, United States

Location

Maricopa Medical Center

Phoenix, Arizona, 85008, United States

Location

University of Colorado at Denver, Teaching

Aurora, Colorado, 80045, United States

Location

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida- Dept. of Surgery

Gainesville, Florida, 32610, United States

Location

Joseph M. Still Research Foundation, Inc.

Augusta, Georgia, 30909, United States

Location

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Burnett Burn Center at The University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 8163, United States

Location

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

Boston, Massachusetts, 02114, United States

Location

New-York Presbyterian Hospital

New York, New York, 10065, United States

Location

Emergency Medicine Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Lehigh Valley Hospital and Health Network

Allentown, Pennsylvania, 18103, United States

Location

Regional Medical Center ,Regional One Health

Memphis, Tennessee, 38103, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77550, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

HarborView Medical Center

Seattle, Washington, 98104, United States

Location

Columbia St. Mary's, Inc.

Milwaukee, Wisconsin, 53211, United States

Location

University Hospital, Department of Plastic Surgery

Ghent, B 9000, Belgium

Location

Klinika popálenin a rekonstrukční chirurgie, Fakultní nemocnice Brno

Brno, 62500, Czechia

Location

Khechinashvili University Hospital - Thermal Injuries

Tbilisi, 0179, Georgia

Location

Unfallkrankenhaus Berlin Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie

Berlin, Germany

Location

BG Universitätsklinikum Bergmannsheil GmbH

Bochum, 44789, Germany

Location

Rambam Medical Center

Haifa, Israel

Location

Hospital A. Cardarelli of Napoli

Napoli, Italy

Location

Ospedale di Cisanello

Pisa, 56125, Italy

Location

Spitalul Clinic de Urgenta de Chirurgie Plastica, Reparatorie si Arsuri

Bucharest, 010713, Romania

Location

Spitalul Clinic de Urgenta "Sf. Ioan"

Bucharest, 042122, Romania

Location

Spitalul Clinic de Urgenta "Bagdasar-Arseni"

Bucharest, 41915, Romania

Location

Related Publications (1)

• Shoham Y, Rosenberg L, Hickerson W, Goverman J, Iyer N, Barrera-Oro J, Lipovy B, Monstrey S, Blome-Eberwein S, Wibbenmeyer LA, Scharpenberg M, Singer AJ. Early Enzymatic Burn Debridement: Results of the DETECT Multicenter Randomized Controlled Trial. J Burn Care Res. 2024 Mar 4;45(2):297-307. doi: 10.1093/jbcr/irad142.

  PMID: 37715999 DERIVED

MeSH Terms

Interventions

Standard of Care; Gels

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Keren David Zarbiv
• Organization: MediWound

kerend@mediwound.com

972-77-9714103

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2014
• First Posted: May 28, 2014
• Study Start: May 27, 2015
• Primary Completion: June 12, 2018
• Study Completion: August 20, 2020
• Last Updated: July 10, 2024
• Results First Posted: June 27, 2023

Record last verified: 2023-06

Locations

US (18); IL (1); IT (2); BE (1); RO (3); GE (1); DE (2); CZ (1)