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Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

SummaryThe impact of the use of loop diuretics to prevent cumulative fluid balance in non‐oliguric patients is uncertain. This is a retrospective study to estimate the association of time‐averaging loop diuretic exposure in a large population of non‐cardiac, critically ill patients with a positive fluid balance (> 5% of body weight). The exposure was loop diuretic and the main outcomes were 28‐day mortality, severe acute kidney injury and successful mechanical ventilation weaning. Time‐fixed and daily time‐varying variables were evaluated with a marginal structural Cox model, adjusting bias for time‐varying exposure and the presence of time‐dependent confounders. A total of 14,896 patients were included. Patients receiving loop diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39–0.81 and baseline variables adjusted hazard ratio 0.53, 95%CI 0.45–0.62); after full adjusting, loop diuretics had no association with 28‐day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74–1.54) or with reducing severe acute kidney injury occurrence during intensive care unit stay – hazard ratio 1.05 (95%CI 0.78–1.42). However, we identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35–1.89). The main results were consistent in the sub‐group analysis for sepsis, oliguria and the study period (2002–2007 vs. 2008–2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant association with mortality. After adjusting for time‐varying variables, the time average of loop diuretic exposure in non‐cardiac, critically ill patients has no association with overall mortality or severe acute kidney injury; however, prolonged mechanical ventilation is a concern.