Outcomes
AKI, readmission, death, pain
FLASH PULMONARY EDEMA, PROGRESSION, GASTROINTESTINAL BLEEDING, RECRUITMENT
The primary outcome was a composite of progression of AKI, receipt of dialysis, or death within 14 days of randomization or hospital discharge. Progression of AKI was defined by achieving a higher KDIGO AKI stage than the stage present at initial randomization (stage 2 represents a doubling of creatinine, stage 3 a tripling of creatinine).Secondary outcomes included the components of the primary outcome (at 14 days and during the entire admission), the proportion of patients who did not receive one or more MOIs for which they were enrolled within 24 h and while AKI was still present, the duration of AKI, the rate of readmission at 30-days, and hospital costs (as determined by internal cost accounting independent of insurance status). We considered AKI resolved when the most recent measured creatinine no longer met AKI criteriaStrength of guidance regarding empiric discontinuation of the MOIs differed by medication class, as well as by the mechanisms by which they influence renal function, prompting us to pre-specify sub-group analyses stratified by the MOI being received at randomization. We further identified key safety outcomes that may be associated with discontinuation of each class of MOI—all within 14 days or hospital discharge. For NSAIDs, we assessed the rate of prescription of opioid analgesics and maximum pain scores. For RAASi, we assessed the maximum achieved systolic and diastolic blood pressure and the rate of intubation (a proxy for flash pulmonary edema). For PPIs, we assessed the rate of blood transfusion (as inappropriate cessation of PPI may increase the risk of gastrointestinal bleeding), the minimum hemoglobin achieved, and maximum pain scores to capture epigastric pain consequent to PPI cessation.Based on data from our prior trial, we expected the primary outcome to occur in 18.2% of control patients and considered a relative reduction of 20–14.6% would be clinically significant. The target sample size of 5060 individuals provided 90% power to detect a difference at least this large, accounting for two interim analyses and potential 10% contamination of intervention across study arms (as providers exposed to alerts might learn to adjust their care for patients in the usual care arm).The original protocol called for two interim analyses, one at 50% recruitment across four teaching hospitals, and one at 50% recruitment at two non-teaching hospitals, as our prior trial showed a potential signal of harm at the non-teaching hospitals. However, despite no harm signal at the initial interim analysis, the IRB did not grant our request to extend the study into the two non-teaching hospitals. We thus completed recruitment entirely in the four teaching hospitals and completed only one interim analysis.