Mortality time frame variability in septic shock clinical trials: A systematic review.

Abstract

Objective: We sought to delineate the mortality outcome time frames reported in septic shock randomized control trials (RCTs).

Design: Systematic review of PubMed, EMBASE, and the Cochrane Database of Systematic Reviews.

Setting: Intensive care units.

Participants: Studies that included adult patients with septic shock.

Interventions: Any type of intervention.

Main variables of interest: Information about the study, specific patient population, type of study intervention, specific intervention, and number of patients. Mortality time frames were analyzed for geographical differences and changes over time.

Results: The search yielded 2660 unique citations. After screening, 132 eligible studies were identified. A total of 234 mortality time frames were collected from the included studies, of which 15 timeframes were unique. The most frequently reported time frame was 28-day mortality (n = 98, 74% of trials), followed by hospital mortality (n = 35, 27%), ICU mortality (n = 30, 23%), and 90-day mortality (n = 29, 22%). The most reported mortality time frame was 28 days in studies from every continent except Africa. The studies published between 2008 and 2013 (25%) more frequently reported hospital and ICU mortality combination than studies published between 2014 and 2019 (11.4%) (P = 0.043).

Conclusions: There was considerable variability in the mortality time frames reported in ICU-based septic shock trials. This variability may lead to under or overestimation of the problem, overlooking the effectiveness of the interventions studied, and further limiting the application of trials and their pooling in meta-analyses. A consensus regarding time frame reporting in septic shock trials is long overdue.