Johnstone Jennie, Meade Maureen, Marshall John, Heyland Daren K, Surette Michael G, Bowdish Dawn Me, Lauzier Francois, Thebane Lehana, Cook Deborah J
Public Health Ontario, Toronto, Ontario Canada ; St. Joseph's Health Center, Toronto, Ontario Canada ; Department of Medicine, University of Toronto, Toronto, Canada.
Department of Medicine, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, Ontario Canada ; Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
Pilot Feasibility Stud. 2015 May 24;1:19. doi: 10.1186/s40814-015-0013-3. eCollection 2015.
Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate.
METHODS/DESIGN: Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 10 colony forming units of GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded.
The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and hospital length of stay, and mortality. The morbidity, mortality, and cost of VAP underscore the need for cost-effective prophylactic interventions. The PROSPECT Pilot Trial is the initial step toward rigorously evaluating whether probiotics decrease nosocomial infections, have no effect, or actually cause infections in critically ill patients.
ClinicalTrials.gov. NCT01782755.
益生菌被定义为摄入后可能对健康有益的活微生物。对益生菌试验的荟萃分析表明，在重症监护病房（ICU）的患者中使用益生菌时，呼吸机相关性肺炎（VAP）的发生率总体降低25%，感染率降低18%。然而，之前的试验规模较小，大多为单中心试验，且存在较高的偏倚风险。在开展一项大规模的严格试验以测试益生菌是有益、有害还是无影响之前，需要进行一项先导试验。PROSPECT先导试验的目的是确定在机械通气的危重症患者中开展一项更大规模试验研究鼠李糖乳杆菌GG的可行性。我们预先确定，更大规模试验的可行性将基于及时招募患者、高方案依从性、最小污染以及可接受的VAP发生率。
方法/设计：纳入预计接受机械通气≥72小时的ICU中年龄≥18岁的患者。如果患者存在益生菌相关感染风险增加、有严格的肠内用药禁忌证、怀孕、之前参加过相关试验或正在接受姑息治疗，则将其排除。在获得知情同意后，患者按1:1的固定比例随机分组，分组块大小不定，按ICU以及内科、外科或创伤入院诊断进行分层。患者通过鼻胃管每天两次接受1×10菌落形成单位的鼠李糖乳杆菌GG（Culturelle，洛辛工业有限公司）或悬浮于自来水中的相同安慰剂。临床和研究人员、患者及其家属均不知情。
该先导试验的主要结局如下：（1）招募成功，（2）方案依从性≥90%，（3）污染≤5%，（4）VAP发生率约为10%。其他临床结局包括VAP、其他感染、腹泻（总体、抗生素相关性和艰难梭菌性）、ICU和住院时间以及死亡率。VAP的发病率、死亡率和成本突出了对具有成本效益的预防性干预措施的需求。PROSPECT先导试验是严格评估益生菌是否能降低危重症患者医院感染、是否无效或实际上是否会导致感染的第一步。
ClinicalTrials.gov。NCT01782755。
