A Study to Evaluate the Efficacy and Safety of NexoBrid in Children With Thermal Burns Compared the Standard of Care

NCT02278718 | Completed Phase 3 Results DMC

• 1 other identifier: MW2012-01-01
• Study Type: interventional
• Target: 145
• Locations: 14 countries
• Sites: 36

Brief Summary

This study will be a two-arms study intending to demonstrate superiority of NexoBrid treatment over SOC in children with thermal burns. The study objective is to evaluate the safety and clinical benefit of NexoBrid in hospitalized children (0-17 years) with deep partial and/or full thickness thermal burns of 1-30% TBSA and to compare NexoBrid to standard of care (SOC).

Conditions

Thermal Burns

Outcome Measures

Primary Outcomes (1)

• Time to Complete Eschar Removal (in Days)

  Measured by a survival analysis of incidence of complete eschar removal as a function of time. Eschar removal will be measured at the end of the debridement starting from randomization date, assessed until complete eschar removal is achieved (in days)

  From randomization date 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 Outcomes (4)

• Incidence of Surgical Excision Performed for Eschar Removal

  Until complete eschar removal has been achieved. Complete eschar removal was achieved within 0.99 days (95% CI: 0.88 to 1.04) for the NexoBrid treatment arm and 5.99 days (95% CI: 2.71 to9.84) for the SOC treatment arm.

• Blood Loss Related to Eschar Removal

  Hematocrit - immediately before each procedure and 4 hrs after its completion. The amount of blood transfused will be summed over all transfusions carried out during the debridement procedure and up to 24 hrs from the end time of the debridement procedure

• Percent Area of Autograft Performed in DPT Wounds - Main Analysis, Patient Level.

  Assessment will be performed by the investigator immediately after each autograft procedure was performed, before application of coverage.

• Incidence of Autograft Performed in Deep Partial Thickness Wounds

  Patient's wounds were assessed until complete healing of all wounds, during the period from complete eschar removal was achieved until complete wound closure. Median time in the population was approx. 4.5 weeks and longest follow up period was of 12 weeks

Study Arms (2)

NexoBrid Gel

EXPERIMENTAL

NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours.

Drug: NexoBrid

Standard of Care

ACTIVE COMPARATOR

Non surgical and Surgical Debridement

Procedure: Standard of Care

Interventions

NexoBrid DRUG

NexoBrid is an enzymatic debriding agent for Eschar Removal.

NexoBrid Gel

Standard of Care PROCEDURE

Surgical or Non-Surgical methods for Eschar Removal

Standard of Care

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Stage 1: Males and females between 4 years to 18 years of age, Stage 2 (upon DSMB review): Males and females between 1 year to 18 years of age, Stage 3 (upon DSMB review): Males and females between 0 years to 18 years of age.
• Thermal burns caused by fire/flame, scalds or contact.
• Patient total burns area ≥ 1% DPT and / or FT,
• Patient total burns area should be ≤ 30% TBSA; SPT, DPT and/or FT in depth,
• Signed written informed consent by a legal guardian can be obtained within 84 hours of the burn injury.
• At least one wound (a continuous burn area which can be treated in one session; might include several anatomical areas) in a patient should meet all following criteria:
• Wound that is ≥ 1% TBSA (DPT and/or FT) (not including face, perineal or genital),
• Wound is composed of DPT and/or FT in depth. Superficial partial thickness areas may be included in the wound area only if cannot be separated from deeper areas (e.g. surrounded by or mixed with DPT areas) and might interfere with the treatment of the deeper areas,
• Wound that is potentially intended for surgical eschar removal,
• Wound's blisters can be unroofed, as judged by the investigator.

You may not qualify if:

• Patients weighing less than 3kg,
• Patients who are unable to follow study procedures and follow up period,
• Patients with electrical or chemical burns,
• Patient with a continuous burn area above 15% TBSA,
• Patients with no DPT and/or FT burn area (only SPT wounds),
• Patient with circumferential anterior/posterior trunk fire/flame burns, \>15% TBSA (Circumferential is defined as encircling ≥ 80% of the trunk circumference),
• The following pre-enrolment dressings: a. Flammacerium, b. Silver Nitrate (AgNO3),
• Patients with diagnosed infections,
• Diagnosis of smoke inhalation injury,
• Patients with pre-enrolment wounds which are covered by eschar saturated with iodine or by SSD pseudoeschar (e.g. pseudoeschar as a result of \>12h SSD treatment),
• Patients with pre-enrolment escharotomy,
• Pregnant women (positive pregnancy test) or nursing mothers,
• Poorly controlled diabetes mellitus (HbA1c\>9%),
• Known Cardio-pulmonary disease, oxygen-dependent pulmonary diseases, broncho-pneumonia, uncontrolled asthma,
• Known conditions which interfere with circulation (peripheral vascular disease, edema, lymphedema, surgery to the regional lymph nodes, obesity),

Sponsors & Collaborators

• MediWound Ltd: lead

Study Sites (36)

Maricopa Special Health Care District

Phoenix, Arizona, 85008, United States

Location

University Of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33146, United States

Location

The University of South Florida Board of Trustees

Tampa, Florida, 33620, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

Shriners Hospital for Children

Boston, Massachusetts, 02114, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Legacy Emanuel Hospital & Health Center dba Legacy Research Institute

Portland, Oregon, 97232, United States

Location

Drexel University

Philadelphia, Pennsylvania, 19134, United States

Location

Shawn Jekins Children's Hospital

Charleston, South Carolina, 29425s, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

University Hospital, Department of Plastic Surgery

Ghent, B 9000, Belgium

Location

S. Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

Unfallkrankenhaus Berlin Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie

Berlin, 12683, Germany

Location

Klinikum Stuttgart - Olgahospital

Stuttgart, D-70176, Germany

Location

MRE Bethesda Gyermekkórháza

Budapest, H-1146, Hungary

Location

B.A.Z Megyei Kórház és Egyetemi Oktatókórház

Miskolc, H-3526, Hungary

Location

Klinikai Kozpont Gyermekgyogyaszati Klinika

Pécs, H-7624, Hungary

Location

Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg

New Delhi, National Capital Territory of Delhi, 110001, India

Location

Krishna Rajendra Hospital

Mysuru, 570001, India

Location

Vardhman Mahavir Medical College (VLCC) and Safdarjung Hospital

New Delhi, 110029, India

Location

Universitary Integrated Hospital Verona (AOUI Verona),

Verona, 37126, Italy

Location

Acute Burn Care &Trauma Surgery, Dept Surgery/Burn Center, Rode Kruis Ziekenhuis, LUMC University Leiden

Beverwijk, 1942, Netherlands

Location

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, 30-663, Poland

Location

Szpital Dzieciecy im.prof.dr.med Jana Bogdanowicza, Oddzial Chirurgii i Urologii Dzieciecej z Pododdzialem Leczenia Oparzen

Warsaw, Poland

Location

Spitalul Clinic de Urgenta pentru Copii "Sfanta Maria"

Iași, 700309, Romania

Location

Spitalul Clinic de Urgenta Tg- Mures

Târgu Mureş, 54000, Romania

Location

Univerzitná nemocnica Bratislava, Klinika popálenin a rekonštrukčnej chirurgie

Bratislava, 826 06, Slovakia

Location

La Paz University Hospital

Madrid, 28046, Spain

Location

Boulevar Sur s/n

Valencia, 46026, Spain

Location

CNPE "City clinical hospital of immediate and urgent medical aid n.a.Meshchaninov" of Kharkiv CC and State institution 'Zaitsev V.T. Institute of general and urgent surgery of the National academy of medical sciences of Ukraine'

Kharkiv, 61103, Ukraine

Location

Communal institution "Odessa Regional Clinical Medical Center"

Odesa, 65049, Ukraine

Location

Birmingham Children´s Hospital NHS Foundation Trust

Birmingham, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Rosenberg L, Krieger Y, Bogdanov-Berezovski A, Silberstein E, Shoham Y, Singer AJ. A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT. Burns. 2014 May;40(3):466-74. doi: 10.1016/j.burns.2013.08.013. Epub 2013 Sep 26.

  PMID: 24074719 BACKGROUND

Related Links

• Related Info

MeSH Terms

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Keren David Zarbiv
• Organization: MediWound

kerend@mediwound.com

972-77-9714103

Study Officials

• Lior Rosenberg, Prof.

  MediWound Ltd

  STUDY CHAIR

• Yaron Shoham, Dr.

  MediWound Ltd

  STUDY DIRECTOR

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: October 30, 2014
• Study Start: May 1, 2015
• Primary Completion: April 1, 2021
• Study Completion: December 1, 2022
• Last Updated: September 27, 2024
• Results First Posted: September 27, 2024

Record last verified: 2024-09

Locations

PL (2); GB (2); BE (1); IT (1); HU (3); IN (3); DE (2); GE (1); SL (1); NL (1); ES (2); US (13); UA (2); RO (2)