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

NCT ID: NCT02278718

Last Updated: 2024-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2022-12-31

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).

Detailed Description

A total of 160 patients will be randomized into NexoBrid and SOC treatment (80 patients per arm).

Age distribution will be managed as follows:

• 45 patients 0-23 months old
• 45 patients 24 months-3 years old
• 30 patients 4-11 years old
• 20 patients 12-17 years old The remaining 20 patients will be enrolled to any of the above groups, per their age during enrollment.

The study will be conducted in three stages. In Stage I, at least 24 children age 4-18 years, hospitalized in burn units, with deep partial thickness burns ranging from 1%-30% TBSA, and who meet the entrance criteria, will be enrolled. Upon completion of stage I, a safety analysis will be performed on safety parameters and the results will be evaluated by a Data Safety Monitoring Board (DSMB) as defined in the agreed charter. If the DSMB does not have any safety concerns, Stage II will commence, this time enrolling at least 26 additional children aged of 1-18 years according to the study procedures. A DSMB will be convened to assess the safety data of the first 50 patients enrolled at stages 1 & 2. If the DSMB has not found any safety concerns, stage III will commence in which patients from the age of birth to 18 years will be included (stage III will include 110 remaining patients required to reach a total of 160 patients).

Following the enrollment of a subject to the study and prior to randomization, physicians will define one or more Target Wounds (TWs) per subject according to TWs definition. All subjects' DPT and FT burns that fit the specified criteria are intended to receive study treatment per randomized study arm and therefore, must be designated as TWs.

Prior to eschar removal treatment with NexoBrid or SOC 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 or SOC, following randomization). Subsequent to eschar removal, all wounds will be assessed and treated in the same manner, in accordance with post-eschar removal wound care strategy. Furthermore, subjects will undergo daily assessments (Vital signs (VS) and pain assessments) for one week and weekly assessments thereafter, until wound closure. Following wound closure, subjects will be followed up at 6 weeks, 12 weeks, and after that, at 6, 12, 18 and 24 months (for a blinded assessment of cosmesis, function and QoL evaluation).

All subjects will be invited to one additional extended follow up visit that will occur at least 30 months after wound closure confirmation for a blinded assessment of cosmesis, function and QoL evaluation.

Conditions

Thermal Burns

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

NexoBrid Gel

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.

Group Type: EXPERIMENTAL

NexoBrid

Intervention Type: DRUG

NexoBrid is an enzymatic debriding agent for Eschar Removal.

Standard of Care

Non surgical and Surgical Debridement

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: PROCEDURE

Surgical or Non-Surgical methods for Eschar Removal

Interventions

NexoBrid

NexoBrid is an enzymatic debriding agent for Eschar Removal.

Intervention Type: DRUG

Standard of Care

Surgical or Non-Surgical methods for Eschar Removal

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. 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.

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

3. Patient total burns area ≥ 1% DPT and / or FT,

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

5. 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:

1. Wound that is ≥ 1% TBSA (DPT and/or FT) (not including face, perineal or genital),

2. 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,

3. Wound that is potentially intended for surgical eschar removal,

4. Wound's blisters can be unroofed, as judged by the investigator.

Exclusion Criteria

1. Patients weighing less than 3kg,

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

3. Patients with electrical or chemical burns,

4. Patient with a continuous burn area above 15% TBSA,

5. Patients with no DPT and/or FT burn area (only SPT wounds),

6. Patient with circumferential anterior/posterior trunk fire/flame burns, >15% TBSA (Circumferential is defined as encircling ≥ 80% of the trunk circumference),

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

8. Patients with diagnosed infections,

9. Diagnosis of smoke inhalation injury,

10. 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),

11. Patients with pre-enrolment escharotomy,

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

13. Poorly controlled diabetes mellitus (HbA1c>9%),

14. Known Cardio-pulmonary disease, oxygen-dependent pulmonary diseases, broncho-pneumonia, uncontrolled asthma,

15. Known conditions which interfere with circulation (peripheral vascular disease, edema, lymphedema, surgery to the regional lymph nodes, obesity),

16. Any known conditions that would preclude safe participation in the study or adding further risk to the basic acute burn trauma (such as immuno-compromising diseases, life threatening trauma, severe pre-existing coagulation disorder, pulmono-cardiovascular, liver or neoplastic disease),

17. ASA greater than 2

18. Chronic systemic steroid intake,

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

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

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

22. Current (within 12 months prior to screening) alcohol (daily consumption > 3 units for males and >2 units for females) or drug abuse,

23. Prisoners and incarcerated

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

25. Patient expresses objection to participate in the study.

26. Patients with other severe cutaneous trauma at the same sites as the burns (i.e. blunt, avulsion or deep abrasion) or previous burn(s) at the same treatment site(s)

27. General condition of patient would contraindicate surgery

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MediWound Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lior Rosenberg, Prof.

Role: STUDY_CHAIR

MediWound Ltd

Yaron Shoham, Dr.

Role: STUDY_DIRECTOR

MediWound Ltd

Locations

Maricopa Special Health Care District

Phoenix, Arizona, United States

University Of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

The University of South Florida Board of Trustees

Tampa, Florida, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Shriners Hospital for Children

Boston, Massachusetts, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Legacy Emanuel Hospital & Health Center dba Legacy Research Institute

Portland, Oregon, United States

Drexel University

Philadelphia, Pennsylvania, United States

Shawn Jekins Children's Hospital

Charleston, South Carolina, United States

University of Utah

Salt Lake City, Utah, United States

Harborview Medical Center

Seattle, Washington, United States

University Hospital, Department of Plastic Surgery

Ghent, , Belgium

S. Khechinashvili University Hospital

Tbilisi, , Georgia

Unfallkrankenhaus Berlin Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie

Berlin, , Germany

Klinikum Stuttgart - Olgahospital

Stuttgart, , Germany

MRE Bethesda Gyermekkórháza

Budapest, , Hungary

B.A.Z Megyei Kórház és Egyetemi Oktatókórház

Miskolc, , Hungary

Klinikai Kozpont Gyermekgyogyaszati Klinika

Pécs, , Hungary

Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg

New Delhi, National Capital Territory of Delhi, India

Krishna Rajendra Hospital

Mysuru, , India

Vardhman Mahavir Medical College (VLCC) and Safdarjung Hospital

New Delhi, , India

Universitary Integrated Hospital Verona (AOUI Verona),

Verona, , Italy

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

Beverwijk, , Netherlands

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, , Poland

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

Warsaw, , Poland

Spitalul Clinic de Urgenta pentru Copii "Sfanta Maria"

Iași, , Romania

Spitalul Clinic de Urgenta Tg- Mures

Târgu Mureş, , Romania

Univerzitná nemocnica Bratislava, Klinika popálenin a rekonštrukčnej chirurgie

Bratislava, , Slovakia

La Paz University Hospital

Madrid, , Spain

Boulevar Sur s/n

Valencia, , Spain

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, , Ukraine

Communal institution "Odessa Regional Clinical Medical Center"

Odesa, , Ukraine

Birmingham Children´s Hospital NHS Foundation Trust

Birmingham, , United Kingdom

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Countries

United States; Belgium; Georgia; Germany; Hungary; India; Italy; Netherlands; Poland; Romania; Slovakia; Spain; Ukraine; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 24074719 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/?term=nexobrid

Related Info

Other Identifiers

MW2012-01-01

Identifier Type: -

Identifier Source: org_study_id