Thermal BurnsPhase 3NCT02148705
A Study to Evaluate the Efficacy and Safety of NexoBrid in Subjects With Thermal Burns
A Phase 3 study testing NexoBrid in people with Thermal Burns, run by MediWound Ltd at 29 sites in 8 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 77 years
- Conditions the study is for
- Thermal Burns
- What is being tested?
- NexoBrid
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 175 participants
- Where
- 29 sitesin 8 countries
- Study dates
- 27 May 2015to 20 Aug 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 77 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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)
- 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).
- Pre-existing diseases which interfere with circulation (severe peripheral vascular disease, edema, lymphedema, regional lymph nodes, significant varicose veins),
- 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)
- Chronic systemic steroid intake,
- History of allergy and/or known sensitivity to pineapples, papaya, Bromelain or papain,
- Current (within 12 months prior to screening) suicide attempt,
- Mentally incapacitated adults who are incapable of giving legal consent
- Enrollment in any investigational drug trial within 4 weeks prior to screening,
- Current (within 12 months prior to screening) alcohol or drug abuse (see definition in section 1.1)
- Prisoners and incarcerated,
- Patients who might depend on the clinical study site or investigator.
Trial locations and contacts
29 sites in 8 countries.
29 sites in 8 countries
United States18 sites
Lehigh Valley Hospital and Health Network
Allentown, Pennsylvania, 18103
Joseph M. Still Research Foundation, Inc.
Augusta, Georgia, 30909
University of Colorado at Denver, Teaching
Aurora, Colorado, 80045
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 8163
The General Hospital Corporation d/b/a Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Florida- Dept. of Surgery
Gainesville, Florida, 32610
University of Texas Medical Branch
Galveston, Texas, 77550
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Burnett Burn Center at The University of Kansas Hospital
Kansas City, Kansas, 66160
Regional Medical Center ,Regional One Health
Memphis, Tennessee, 38103
Columbia St. Mary's, Inc.
Milwaukee, Wisconsin, 53211
University of South Alabama Department of Surgery
Mobile, Alabama, 36617
New-York Presbyterian Hospital
New York, New York, 10065
Maricopa Medical Center
Phoenix, Arizona, 85008
University of Utah Hospital
Salt Lake City, Utah, 84132
HarborView Medical Center
Seattle, Washington, 98104
Emergency Medicine Stony Brook University Hospital
Stony Brook, New York, 11794
Medstar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Romania3 sites
Spitalul Clinic de Urgenta de Chirurgie Plastica, Reparatorie si Arsuri
Bucharest, 010713
Spitalul Clinic de Urgenta "Sf. Ioan"
Bucharest, 042122
Spitalul Clinic de Urgenta "Bagdasar-Arseni"
Bucharest, 41915
Germany2 sites
Unfallkrankenhaus Berlin Zentrum für Schwerbrandverletzte mit Plastischer Chirurgie
Berlin
BG Universitätsklinikum Bergmannsheil GmbH
Bochum, 44789
Italy2 sites
Hospital A. Cardarelli of Napoli
Naples
Ospedale di Cisanello
Pisa, 56125
Belgium1 site
University Hospital, Department of Plastic Surgery
Ghent, B 9000
Czechia1 site
Klinika popálenin a rekonstrukční chirurgie, Fakultní nemocnice Brno
Brno, 62500
Georgia1 site
Khechinashvili University Hospital - Thermal Injuries
Tbilisi, 0179
About this study
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
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:
- To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing complete eschar removal as compared with Gel vehicle,
- 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,
- 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.
Read the 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.
- Conditions
- Thermal Burns
- Being tested
- NexoBrid, Standard of Care (SOC), Gel Vehicle
- Keywords
- fire/flame, scalds, contact
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NexoBridDrug
Standard of Care (SOC)Procedure or surgery
Gel VehicleDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Procedure: Standard of Care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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).
Measured: 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
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)
Measured: 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)
Comparison of NexoBrid over SOC with regard to the blood loss (volume in mL) occurred during the eschar removal procedures.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2014 (estimated)
- Study start27 May 2015
- Primary completion12 Jun 2018
- Study completion20 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thermal BurnsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- MediWound Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02148705
- Sponsor's protocol ID
- MW 2010-03-02
- Status last verified
- Jun 2023
- First submitted
- 22 May 2014
- Last updated
- 10 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 37715999
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02148705
- Acronym / sponsor ID
- MW 2010-03-02
- Conditions
- Thermal Burns
- Keywords
- fire/flame, scalds, contact
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- MediWound LtdIndustry (pharma, biotech, devices)
- Study start
- 27 May 2015 (actual)
- Primary completion
- 12 Jun 2018 (actual)
- Study completion
- 20 Aug 2020 (actual)
- First posted
- 28 May 2014 (estimated)
- Results
- Posted 27 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing complete eschar removal as compared with Gel vehicle,
- 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,
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NexoBrid Gel | Experimental | Drug: NexoBridNexoBrid 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. |
| Gel Vehicle | Placebo comparator | Drug: Gel 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. |
| Standard of Care (SOC) | Active comparator | Procedure: 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. |
Who may qualify
- Ages
- 18 to 77 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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,
Key exclusion criteria (26 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NexoBrid | Drug | NexoBrid Gel |
| Standard of Care (SOC) | Procedure or surgery | Standard of Care (SOC) |
| Gel Vehicle | Drug | Gel Vehicle |
Primary outcome
Primary Endpoint: Number of Participants With Complete Eschar Removal.
Time frame: 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.
3 secondary outcomes
Secondary Endpoint: Number of Participants With Surgical Excision Performed or Eschar Removal for NexoBrid vs SOC (FAS)
Time frame: 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
Time frame: 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)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37715999Shoham 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NexoBrid in people with Thermal Burns, run by MediWound Ltd at 29 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Romania, Germany, Italy, Belgium and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Endpoint: Number of Participants With Complete Eschar Removal. (time frame: post application (post 2 h soaking)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02148705, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.