Coenrolment in a Stress Ulcer Prophylaxis Trial: Protocol for a Substudy of Characteristics and Consequences

Abstract Background Coenrolment is defined as the enrolment of an individual patient into more than one study. This protocol describes a study of coenrolment nested in a randomized, blinded, parallel-group trial of stress ulcer prophylaxis comparing the effect of pantoprazole versus placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding, and the primary safety outcome of 90-day all-cause mortality. The objective of this study is to determine the characteristics of patients, centers and studies involved in coenrolment, and the association of coenrolment with trial metrics and patient outcomes. Methods This is a pre-planned study with 5 specific aims and a priori hypotheses. The aims are to analyze: 1) the informed consent model of the coenrolled studies, timing of coenrolment, coenrolled study affiliation, and coenrolled study funding; 2) the characteristics of patients and centers involved in coenrolment versus not involved in coenrolment; 3) the association of coenrolment with adverse events; 4) the effect of coenrolment on protocol deviations; and 5) the impact of coenrolment on the effect of pantoprazole on the primary efficacy outcome (upper gastrointestinal bleeding) and the primary safety outcome (90-day mortality). We will use descriptive analyses and regression analysis to examine patterns and predictors of coenrolment. Results All 4821 trial participants will be included in this trial, 1719 (35.7%) of whom were coenrolled in at least one other study. Conclusions Among invasively ventilated patients in this stress ulcer prophylaxis trial, we will generate much needed empiric evidence about coenrolment in critically ill patients. These data will help to inform future guidance documents on this topic.