FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trial

Abstract

Introduction0.9% saline and Ringer’s lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and death. Few large multicentre randomised trials have been conducted to evaluate the effect of these two fluids on clinically important outcomes.MethodsFLUID is a pragmatic pilot cluster randomised crossover trial in which four hospitals will be randomised to normal saline or Ringer’s lactate for 14 weeks, then crossover to the alternative fluid for the subsequent 14 weeks after 1 to 3 week transition. With waiver of informed consent, all adult and paediatric patients admitted to participating sites will be included in the FLUID trial except for neonates. Primary feasibility outcome is study fluid protocol adherence (target:≥80%). Secondary feasibility outcomes include time to research ethics board (REB) approval and readiness to trial initiation (≤3 months from REB submission and approval). Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes for the future large FLUID trial will be described. Protocol adherence will be collected by site at specified time points. All clinical data will be obtained at patient level through provincial health administrative data held at the Institute for Clinical Evaluative Sciences (ICES). Event rates for the primary and secondary outcomes will be described using frequencies and proportions with 95% CIs. Intracluster and interperiod correlation coefficients will be calculated from population-level data available at ICES.Ethics and disseminationThe study protocol has been approved by the Ottawa Health Science Research Ethics Board. The FLUID pilot will determine feasibility, and ICES data across all potential sites in Ontario will allow calculation of sample size parameter estimates to inform the design and implementation of the large trial.Trial registration numberNCT02721485; Pre-results.

Developing a framework for the ethical design and conduct of pragmatic trials in healthcare: a mixed methods research protocol

“…The FLUID trial is a pragmatic cluster randomized cross-over trial comparing resuscitation with Ringer’s Lactate versus normal saline on death and hospital readmissions in hospitalized patients, with outcomes assessed using health administrative data [ 28 ]. Both fluids are considered usual care interventions that have been available for decades and are administered to many hospitalized patients.…”

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer’s lactate

“…These calculations include varying within and between cluster correlation co-efficients which are required for cluster RCT sample size calculations. 29 The 1% absolute difference is very small and was agreed to by our FLUID team, the CCCTG and our patient partners as these differences are highly important at the population (hospital or healthcare system) level with thousands of hospital admissions every year.…”

“…A standardised strategy for site trial preparation and conduct was implemented and is summarised in detail in the published FLUID protocol BMJ Open 2018;8;e022780.doi.1136/bmjopen-2018-022780. 29 …”

“…In advance of FLUID trial start-up at each participating hospital, several communication strategies were implemented to ensure all key stakeholders (staff physicians, trainees, nurses) were educated about FLUID, 29 BMJ Open 2018;8;e022780.doi.1136/bmjopen-2018-022780). These communication strategies ensured that physicians and nurses knew there was a small amount of the non-allocated study fluid available for use throughout the hospital if the treating physician chose to opt out of using the study fluid for a given patient.…”

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials

“…Different consent models have been used in prior cluster randomized crossover trials (CRXO), including traditional consent models [ 5 , 6 ], waiver of consent [ [7] , [8] , [9] ], and deferred consent models [ [10] , [11] , [12] ]. The selection of a consent model varies based on the patient population, the level of risk associated with the intervention, the study outcomes and the data collection requirements.…”