Fluids in Septic Shock

The Fluids in Septic Shock (FISSH) randomized controlled trial (RCT) aims to determine the impact of using Ringer’s lactate (RL) as compared with 0.9% normal saline (NS) on 30-day mortality and other end points in critically ill adults with septic shock. What are the rationale, methodology, ethics, implementation, and statistical analysis of the FISSH trial? The FISSH trial is an international, randomized, concealed allocation, masked, parallel-group, individual patient RCT. Eligible patients are critically ill adults aged ≥ 16 years who require fluid resuscitation for hypotension or organ hypoperfusion, have a clinical suspicion of infection, and are within 6 hours of emergency department presentation or within 6 hours of consultation by the critical care team for patients from the ward. Participants are randomized to receive either RL or NS for all maintenance and bolus fluids as needed throughout the ICU stay. The primary outcome is 30-day mortality. Secondary outcomes include acute kidney injury, length of ICU and hospital stays, and receipt of organ support. After an interim analysis of results from 548 patients (50% total), the data safety monitoring board recommended continuing the trial. The FISSH trial is conducted in collaboration with the Canadian Critical Care Trials Group. The FISSH trial was launched in October 2017. As of May 12, 2025, 1,019 patients (91.1%) of the target sample size of 1,118 patients have been recruited from 29 study centers. We anticipate recruitment to be complete by the end of 2025. This protocol and statistical analysis plan outlines the design and conduct of the international FISSH randomized controlled trial. The FISSH trial may inform clinical practice guidelines worldwide. ClinicalTrials.gov ; No.: NCT03677102; URL: www.clinicaltrials.gov