What a negative trial does not tell us: Bayesian reanalysis of the enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients randomized clinical trial
Abstract
BACKGROUND
The enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients (IMMUNOCITRE) randomized controlled trial, evaluating the immune effect of restoring arginine deficiency through enteral administration of citrulline in critically ill patients, found no statistically significant difference in Day-7 SOFA score between enteral L-citrulline and placebo in mechanically ventilated ICU patients (p = 0.9). The trial was likely underpowered due to lower-than-expected baseline SOFA scores. We conducted a post hoc Bayesian reanalysis to quantify the posterior probability of benefit and characterize the residual uncertainty beyond the binary frequentist result.
METHODS
We performed a Bayesian reanalysis of all patients from the IMMUNOCITRE trial that included 120 mechanically ventilated ICU patients without sepsis or septic shock from four French intensive care units (ICU). Patients received either enteral L-citrulline (5 g twice daily for 5 days) or isonitrogenous, isocaloric placebo. Three prior distributions were specified to reflect optimistic, neutral, and pessimistic pre-existing beliefs about treatment benefit. The primary outcome (Day-7 SOFA score) was modelled as an ordinal variable using a Bayesian cumulative proportional-odds model adjusted for baseline Day-1 SOFA score. To account for competing terminal events without introducing survivor bias, patients who died before Day 7 were assigned a penalized…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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