Duffett Mark, Choong Karen, Foster Jennifer, Gilfoyle Elaine, Lacroix Jacques, Pai Nikhil, Thabane Lehana, Cook Deborah J
Departments of Pediatrics and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario Canada.
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia Canada.
Pilot Feasibility Stud. 2017 May 19;3:26. doi: 10.1186/s40814-017-0142-y. eCollection 2017.
Despite sparse pediatric data on effectiveness, the majority of critically ill children receive medications to prevent gastrointestinal (GI) bleeding. Stress ulcer prophylaxis may have unintended consequences-increasing the risk of nosocomial infections-which may be more serious and common than the bleeding which these drugs are prescribed to prevent. Randomized controlled trials (RCTs) in pediatric critical care are exceptionally challenging to complete, thus a rigorous pilot RCT is crucial. The objective of this pilot RCT is to assess the feasibility of a large multicentre RCT of stress ulcer prophylaxis with pantoprazole to prevent upper GI bleeding vs. placebo.
A multi-centre blinded pilot RCT of 120 children in six Canadian PICUs. Children expected to require mechanical ventilation for more than 48 h will be randomized to receive intravenous pantoprazole 1 mg/kg or identical placebo once daily until they no longer need mechanical ventilation. We have four feasibility outcomes and will consider the trial successful if we achieve:Effective screening: If >80% of eligible patients are approached for consent.Timely enrollment: if >80% of participants receive their first dose of the assigned study drug within 1 day of becoming eligible.Participant accrual: If the average monthly enrolment is two or more participants per centre per month.Protocol adherence: if >90% of doses are administered according to the protocol.
There are many uncertainties about the risks and benefits of stress ulcer prophylaxis. In an era of widespread use-where clinicians prescribe prophylaxis to the more severely ill-a large, rigorous RCT is required. A trial to determine if a strategy of withholding stress ulcer prophylaxis is not inferior to a strategy of routine stress ulcer prophylaxis will be challenging. A carefully designed and implemented pilot trial is essential.
ClinicalTrials.gov:NCT02929563 (Registered October 3, 2016).
尽管关于疗效的儿科数据稀少，但大多数危重症儿童都接受预防胃肠道（GI）出血的药物治疗。应激性溃疡预防可能会产生意想不到的后果——增加医院感染风险——这可能比这些药物所预防的出血更为严重和常见。在儿科重症监护中完成随机对照试验（RCT）极具挑战性，因此严格的预试验RCT至关重要。这项预试验RCT的目的是评估一项大型多中心RCT的可行性，该RCT比较泮托拉唑预防应激性溃疡以防止上消化道出血与安慰剂的效果。
在加拿大六个儿科重症监护病房对120名儿童进行多中心双盲预试验RCT。预计需要机械通气超过48小时的儿童将被随机分组，接受每日一次静脉注射泮托拉唑1mg/kg或相同的安慰剂，直至不再需要机械通气。我们有四个可行性指标，如果达到以下标准，将认为试验成功：有效筛查：如果>80%符合条件的患者被邀请签署知情同意书。及时入组：如果>80%的参与者在符合条件的1天内接受第一剂分配的研究药物。参与者招募：如果平均每月每个中心招募两名或更多参与者。方案依从性：如果>90%的剂量按照方案给药。
关于应激性溃疡预防的风险和益处存在许多不确定性。在广泛使用的时代——临床医生对病情较重的患者进行预防治疗——需要进行一项大型、严格的RCT。确定不进行应激性溃疡预防策略是否不劣于常规应激性溃疡预防策略的试验将具有挑战性。精心设计和实施的预试验至关重要。
ClinicalTrials.gov：NCT02929563（2016年10月3日注册）。
