Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: the multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT)

Abstract

IntroductionThe effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain.Methods and analysisThe Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60.Ethics and disseminationROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results.

Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT)

“…The investigator initiated ROCIT study was a parallel group, placebo-controlled, randomised clinical trial conducted in the ICUs of five hospitals in Perth, Western Australia (ANZCTR 12617000783325). The protocol was prospectively approved by the research ethics committee (HREC) of all participating institutions and reported prior to completion of the study (South Metropolitan Health Service Human Research Ethics Committee ref:RGS000004, St John of God Health Care Human Research Ethics Committee ref:1183) [ 12 ]. Initial HREC approval had included the provision to enrol participants who lacked capacity to provide informed consent, where prospective consent was able to be obtained from the person responsible.…”

“…In the placebo group, a mean DAOH 60 of 37 and standard deviation (SD) of nine was assumed, using previous estimates from the lead study site [ 12 ]. Based on a two-sided type I error rate of 0.05 and sample size inflation of 20% to account for rank-based testing, a further 5% each for withdrawn consent and loss to follow-up, a sample size of 220 participants was determined to have 80% power to detect a between-group difference in DAOH 60 of 4 days.…”

“…Based on a two-sided type I error rate of 0.05 and sample size inflation of 20% to account for rank-based testing, a further 5% each for withdrawn consent and loss to follow-up, a sample size of 220 participants was determined to have 80% power to detect a between-group difference in DAOH 60 of 4 days. This difference was considered clinically meaningful to ICU consumers [ 12 ].…”