Stress ulcer prophylaxis versus placebo—a blinded randomized control trial to evaluate the safety of two strategies in critically ill infants with congenital heart disease (SUPPRESS-CHD)

BACKGROUND: Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia, and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit. METHODS: A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 h. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age < 30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study. DISCUSSION: Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined, and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of withholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03667703. Registered 12 September 2018, https://clinicaltrials.gov/ct2/show/NCT03667703?term=SUPPRESS+CHD&draw=2&rank=1. All WHO Trial Registration Data Set Criteria are met in this manuscript.