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

Thermal Burns Clinical Trial

Official title:

A Multicenter, Multinational, Randomized, Controlled, Assessor Blinded Study, Performed in Subjects With Thermal Burns, to Evaluate the Efficacy and Safety of NexoBrid Compared to Gel Vehicle and Compared to Standard of Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02148705
• Other study ID #: MW 2010-03-02
• Status: Completed
• Phase: Phase 3
• Start date: May 27, 2015
• Est. completion date: August 20, 2020

Study information

• Verified date: June 2023
• Source: MediWound Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: August 20, 2020
• Est. primary completion date: June 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 77 Years

Eligibility

Inclusion Criteria- Patient level

1. Males and females; = 18

2. Thermal burns caused by fire/flame, scalds or contact,

3. Patient total burns area = 3% DPT and / or FT,

4. Patient total burns area should be = 30% TBSA; SPT, DPT and/or FT in depth,

5. Informed consent can be obtained within 84 hours of the burn injury,

6. Patients who are willing and able to sign a written consent form.

Inclusion Criteria - Wound level

1. 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:

2. SPT area that cannot be demarcated from DPT and FT areas should be less than 50% of the % TBSA of the TW.

3. Wound's blisters can be removed/ unroofed, as judged by the investigator.

Exclusion Criteria- Patient level

1. Patients who are unable to follow study procedures and follow up period.

2. Modified Baux index = 80,

3. Patients with burned charred fingers, 3rd degree in depth and possibly devoid of circulation,

4. Patients with abraded wound/s that cannot be treated by an enzymatic debrider application (NexoBrid) will be excluded from the study,

5. Patients with electrical or chemical burns,

6. 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.

7. The following pre-enrollment dressings: a. Flammacerium, b. Silver Nitrate (AgNO3),

8. 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),

9. Patients with pre-enrollment escharotomy.

10. Patients with diagnosed infections as described in Section 11.9 of study protocol,

11. Diagnosis of smoke inhalation injury.

12. Pregnant women (positive pregnancy test) or nursing mothers.

13. Poorly controlled diabetes mellitus (HbA1c>11%) in patients with known diabetes as captured in the medical history.

14. 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.

15. ASA greater than 2 (Appendix 13- ASA classification system)

16. Cardio-pulmonary disease (MI within 6 months prior to injury, severe pulmonary hypertension, severe COPD or pre-existing oxygen-dependent pulmonary diseases, severe broncho-pneumonia within 1 month prior to injury , steroid dependent asthma or uncontrolled asthma).

17. Pre-existing diseases which interfere with circulation (severe peripheral vascular disease, edema, lymphedema, regional lymph nodes, significant varicose veins),

18. Any conditions that would preclude safe participation in the study or adding further risk to the basic acute burn trauma (such as severe immuno-compromising diseases, life threatening trauma, severe pre-existing coagulation disorder,severe cardiovascular disorder,significant pulmonary disorder, significant liver disorder including post alcoholic abuse impaired function or neoplastic disease, blast injury)

19. Chronic systemic steroid intake,

20. History of allergy and/or known sensitivity to pineapples, papaya, Bromelain or papain,

21. Current (within 12 months prior to screening) suicide attempt,

22. Mentally incapacitated adults who are incapable of giving legal consent

23. Enrollment in any investigational drug trial within 4 weeks prior to screening,

24. Current (within 12 months prior to screening) alcohol or drug abuse (see definition in section 1.1)

25. Prisoners and incarcerated,

26. Patients who might depend on the clinical study site or investigator.

Related Conditions & MeSH terms

• Burns
• Thermal Burns

Intervention

Drug:
• NexoBrid

Procedure:
• Standard of Care (SOC)

Drug:
• Gel Vehicle

Locations

Country	Name	City	State
Belgium	University Hospital, Department of Plastic Surgery	Gent
Czechia	Klinika popálenin a rekonstrukcní chirurgie, Fakultní nemocnice Brno	Brno
Georgia	Khechinashvili University Hospital - Thermal Injuries	Tbilisi
Germany	Unfallkrankenhaus Berlin Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie	Berlin
Germany	BG Universitätsklinikum Bergmannsheil GmbH	Bochum
Israel	Rambam Medical Center	Haifa
Italy	Hospital A. Cardarelli of Napoli	Napoli
Italy	Ospedale di Cisanello	Pisa
Romania	Spitalul Clinic de Urgenta "Bagdasar-Arseni"	Bucharest
Romania	Spitalul Clinic de Urgenta "Sf. Ioan"	Bucharest
Romania	Spitalul Clinic de Urgenta de Chirurgie Plastica, Reparatorie si Arsuri	Bucharest
United States	Lehigh Valley Hospital and Health Network	Allentown	Pennsylvania
United States	Joseph M. Still Research Foundation, Inc.	Augusta	Georgia
United States	University of Colorado at Denver, Teaching	Aurora	Colorado
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	The General Hospital Corporation d/b/a Massachusetts General Hospital	Boston	Massachusetts
United States	University of Florida- Dept. of Surgery	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	The University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Burnett Burn Center at The University of Kansas Hospital	Kansas City	Kansas
United States	Regional Medical Center ,Regional One Health	Memphis	Tennessee
United States	Columbia St. Mary's, Inc.	Milwaukee	Wisconsin
United States	University of South Alabama Department of Surgery	Mobile	Alabama
United States	New-York Presbyterian Hospital	New York	New York
United States	Maricopa Medical Center	Phoenix	Arizona
United States	University of Utah Hospital	Salt Lake City	Utah
United States	HarborView Medical Center	Seattle	Washington
United States	Emergency Medicine Stony Brook University Hospital	Stony Brook	New York
United States	Medstar Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
MediWound Ltd

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Georgia,  Germany,  Israel,  Italy,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Secondary Endpoint: Number of Participants With Surgical Excision Performed or Eschar Removal for NexoBrid vs SOC (FAS)	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).	Post application (post 2 h soaking) for NexoBrid arm and immediately post surgical excision for SOC arm.
Secondary	Secondary Endpoint: Comparison of Time (Days) to Complete Eschar Removal	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)	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	Secondary Endpoint: Patient-Level Comparison of Actual Blood Loss (Volume in mL) Related to Eschar Removal for NexoBrid vs SOC (FAS)	Comparison of NexoBrid over SOC with regard to the blood loss (volume in mL) occurred during the eschar removal procedures.	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.