Dataset Information

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).

ABSTRACT:

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.

SUBMITTER: Mills KI

PROVIDER: S-EPMC7322718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStress ulcer prophylaxis is commonly used in pediatric critical care, to prevent upper gastrointestinal bleeding. The most frequently used agents are histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). The risk-benefit ratio for stress ulcer prophylaxis is uncertain, because data from randomized clinical trials (RCTs) on the effectiveness and harms of prophylaxis in children are limited.ObjectiveTo describe the views of Canadian pediatric intensivists about a future RCT of stress ulcer prophylaxis.MethodsWe conducted an online survey of Canadian pediatric critical care physicians. We e-mailed information about the study and a link to a 10-item survey to 111 potential respondents, with 2 reminders for nonrespondents. We assessed the relationship between respondents' characteristics and their views about the need for and potential participation in a trial using logistic regression and assessed regional differences using the χ2 test.ResultsThe 68 physicians who replied (61% of potential respondents) had a median of 12 (interquartile range 5-20) years of experience. Forty-four (65%) of the respondents stated that a large, rigorous RCT of stress ulcer prophylaxis in children is needed, and 94% (62 of 66) indicated that it should include a placebo group. The 3 most common designs suggested were a 3-arm trial comparing PPI, H2RA, and placebo (56% [37 of 66 respondents to this question]) and 2-arm trials comparing PPI with placebo (15% [n = 10]) and H2RA with placebo (8% [n = 5]). The 5 patient groups that respondents most commonly stated should be excluded (because they should not receive placebo) were children receiving acid suppression at home (66% [42 of 64 respondents to this question]) or corticosteroids (59% [n = 38]), those with severe coagulopathy or receiving extracorporeal membrane oxygenation (both 36% [n = 23]), and those with burns (31% [n = 20]). Most respondents indicated a willingness to participate in an RCT (64% [42 of 66 respondents to this question]), whereas some (29% [n = 19]) indicated that participation would depend on trial design or funding; only 8% (n = 5) were disinclined to participate.ConclusionsThere is considerable interest in a placebo-controlled RCT of stress ulcer prophylaxis among pediatric critical care physicians in Canada, but consensus on key elements of the trial design is needed.

Project description:PurposeStress ulcer prophylaxis (SUP) is commonly prescribed in the intensive care unit. However, data from systematic reviews and conventional meta-analyses are limited by imprecision and restricted to direct comparisons. We conducted a network meta-analysis of randomized clinical trials (RCTs) to examine the safety and efficacy of drugs available for SUP in critically ill patients.MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials through April 2017 for randomized controlled trials that examined the efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date or language restrictions were applied. Data on study characteristics, methods, outcomes, and risk of bias were abstracted by two reviewers.ResultsOf 96 potentially eligible studies, we included 57 trials enrolling 7293 patients. The results showed that PPIs are probably more effective for preventing clinically important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95% confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13, 0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence). There were no convincing differences among H2RA, sucralfate, and placebo. PPIs probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27; 95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR 1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar across interventions (moderate quality). Estimates of baseline risks of bleeding varied significantly across studies, and only one study reported on Clostridium difficile infection. Definitions of pneumonia varied considerably. Most studies on sucralfate predate pneumonia prevention strategies.ConclusionsOur results provide moderate quality evidence that PPIs are the most effective agents in preventing CIB, but they may increase the risk of pneumonia. The balance of benefits and harms leaves the routine use of SUP open to question.

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Project description:BackgroundProton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults.MethodsLiterature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed.ResultsTwenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR)?=?0.58; 95% confidence intervals (CI): 0.42-0.81] and overt GI bleeding (RR?=?0.48; 95% CI: 0.36-0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31-0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23-1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR?=?0.61; 95% CI: 0.44-0.85; TSA-adjusted CI: 0.16-2.38) and overt GI bleeding (RR?=?0.64; 95% CI: 0.42-0.96; TSA-adjusted CI: 0.12-3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR?=?0.37; 95% CI: 0.25-0.55; TSA-adjusted CI: 0.22-0.63), but not the clinically important GI bleeding (RR?=?0.27; 95% CI: 0.04-2.09).ConclusionsSUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

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