A Multicenter, Multinational, Randomized, Controlled, Open Label Study, Performed in Children With Thermal Burns, to Evaluate the Efficacy and Safety of NexoBrid as Compared to Standard of Care (SOC) Treatment
试验速览
- 阶段
- 3 期
- 入组人数
- 145
- 试验地点
- 36
- 主要终点
- Time to Complete Eschar Removal (in Days)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 0 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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),
- •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),
- •ASA greater than 2
- •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,
- •Enrollment in any investigational drug trial within 4 weeks prior to screening,
- •Current (within 12 months prior to screening) alcohol (daily consumption > 3 units for males and >2 units for females) or drug abuse,
- •Prisoners and incarcerated
- •Patients who might depend on the clinical study site or investigator.
- •Patient expresses objection to participate in the study.
- •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)
- •General condition of patient would contraindicate surgery
研究组 & 干预措施
Standard of Care
Non surgical and Surgical Debridement
干预措施: Standard of Care (Procedure)
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.
干预措施: NexoBrid (Drug)
结局指标
主要结局
Time to Complete Eschar Removal (in Days)
时间窗: 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.
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)
次要结局
- 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)