REVISE:Re-Evaluating theInhibition ofStressErosions in the ICU: a randomised trial protocol (original) (raw)
Related papers
Acta Anaesthesiologica Scandinavica, 2019
Background The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report one-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. Methods In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40 mg vs. placebo (saline) once daily during their ICU stay. We assessed mortality at one year and did sensitivity analyses according to the trial protocol and statistical analysis plan. Accepted Article This article is protected by copyright. All rights reserved. Results A total of 3261 of the 3291 patients with available data (99.1%) were followed up at one year after randomisation; 1635 were allocated to pantoprazole and 1626 to placebo. At one year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01; 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole versus placebo on one-year mortality in the predefined subgroups, i.e. patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs. surgical ICU patients. Conclusion We did not observe a difference in one-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay.
Critical care medicine, 2017
A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients. In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials. Ninety-one pati...
Annals of Saudi medicine
Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increase infections. Therefore, a large randomized clinical trial (RCT) is needed to inform modern practice. The aim of this multicenter pilot trial is to determine the feasibility of performing a large RCT to investigate the efficacy and safety of withholding intravenous pantoprazole. We will include adult critically ill patients who have an anticipated duration of ventilation of >=48 hours. We will exclude patients with acute or recent GI bleeding, pregnancy, dual antiplatelet therapy, poor prognosis or intent to withdraw life support, or previous enrolment in this or a confounding trial. Following informed consent, patients will be randomized to receive ...
Critical Care, 2016
Background: The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill. Methods: We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome. Results: In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I 2 = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I 2 = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I 2 = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I 2 = 0 %, moderate confidence), or ICU length of stay (mean difference (MD),-0.38 days; 95 % CI-1.49, 0.74; P = 0.51; I 2 = 30 %, low confidence). No RCT reported Clostridium difficile infection. Conclusions: PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.
Trials
Background Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and...
Trials, 2016
Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable. The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastr...
Acta Anaesthesiologica Scandinavica, 2018
Background: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. Methods: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. Conclusions: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.
Intensive Care Medicine, 2003
Objective: To compare the rates of clinically significant gastrointestinal bleeding and the number of blood units and endoscopies required for gastrointestinal hemorrhage between patients receiving or not receiving stress-ulcer prophylaxis. Design: Historical observational study comparing two consecutive periods: with (phase 1) and without stress-ulcer prophylaxis (phase 2). Design and setting: A 17-bed intensive care unit in a university teaching hospital. Patients: In phase 1 there were 736 patients and in phase 2 737. Those in the two phases were comparable in age and reason for admission; clinically significant gastrointestinal bleeding rates did not differ between the two phases, but patients in phase 2 were more severely ill. Measurements and results: Comparable numbers of blood units were transfused per bleeding patient in the two phases, especially for patients with significant gastrointestinal bleeding. During each phase 19 fibroscopies were performed for significant bleeding, and two patients required surgery. The clinically significant gastrointestinal bleeding rate and outcome did not differ in patients with at least one risk factor. Total expenditures directly related to gastrointestinal bleeding were similar during the two phases; the total cost incurred by stress-ulcer prophylaxis was estimated at € 6700. Conclusions: Our results suggest that stress-ulcer prophylaxis does not influence the clinically significant gastrointestinal bleeding rate in intensive care unit patients or the cost of its management.
Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU
New England Journal of Medicine
BACKGROUND Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P = 0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621.
Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses
JAMA: The Journal of the American Medical Association, 1996
Critically ill patients are at risk of developing stress ulcers in the upper digestive tract. Multiple risk factors have been associated with the development of this condition, with variable risk of association. Decades of research have suggested the benefit of using pharmaco logic prophylaxis to reduce the incidence of clinically important upper gastrointestinal bleeding, with no reduction in overall mortality. It has been the standard of care to provide prophylaxis to patients at risk. Options for prophylaxis include: proton -pump inhibitors, histamine 2 -receptor antagonists, or sucralfate. The choice of prophylaxis depends on multiple factors including the presence of risk factors, risk for nosocomial pneumonia, and possibly cost.