Dataset Information

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

ABSTRACT:

Background

The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.

Objective

To outline the statistical analysis plan for the REVISE trial.

Methods

REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated.

Results

The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment.

Conclusions

This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide.

Trial registration

www.

Clinicaltrials

gov NCT03374800. November 21, 2017.

SUBMITTER: Heels-Ansdell D

PROVIDER: S-EPMC10701941 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

Heels-Ansdell Diane D Billot Laurent L Thabane Lehana L Alhazzani Waleed W Deane Adam A Guyatt Gordon G Finfer Simon S Lauzier François F Myburgh John J Young Paul P Arabi Yaseen Y Marshall John J English Shane S Muscedere John J Ostermann Marlies M Venkatesh Bala B Zytaruk Nicole N Hardie Miranda M Hammond Naomi N Knowles Serena S Saunders Lois L Poole Alexis A Al-Fares Abdulrahman A Xie Feng F Hall Richard R Cook Deborah D

Trials 20231206 1

<h4>Background</h4>The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.<h4>Objective</h4>To outline the statistical analysis plan for the REVISE trial.<h4>Methods</h4>REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expec ...[more]

PMID: 38057875

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Project description:BackgroundCritically 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 other outcomes in patients with and without COVID-19 infection.MethodsThe ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.DiscussionProphylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.Trial registrationREVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].

Project description:BackgroundMajor Outcomes with Personalized Dialysate TEMPerature (MyTEMP) is a 4-year cluster-randomized clinical trial comparing the effect of using a personalized, temperature-reduced dialysate protocol versus a dialysate temperature of 36.5°C on cardiovascular-related death and hospitalization. Randomization was performed at the level of the dialysis center ("the cluster").ObjectiveThe objective is to outline the statistical analysis plan for the MyTEMP trial.DesignMyTEMP is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized trial.SettingA total of 84 dialysis centers in Ontario, Canada.PatientsApproximately 13 500 patients will have received in-center hemodialysis at the 84 participating dialysis centers during the trial period (April 3, 2017, to March 1, 2021, with a maximum follow-up to March 31, 2021).MethodsPatient identification, baseline characteristics, and study outcomes will be obtained primarily through Ontario administrative health care databases held at ICES. Covariate-constrained randomization was used to allocate the 84 dialysis centers (1:1) to the intervention group or the control group. Centers in the intervention group used a personalized, temperature-reduced dialysate protocol, and centers in the control group used a fixed dialysate temperature of 36.5°C.OutcomesThe primary outcome is a composite of cardiovascular-related death or major cardiovascular-related hospitalization (defined as a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) recorded in administrative health care databases. The key secondary outcome is the mean drop in intradialytic systolic blood pressure, defined as the patients' predialysis systolic blood pressure minus their nadir systolic blood pressure during the dialysis treatment. Anonymized data on patients' predialysis and intradialytic systolic blood pressure were collected at monthly intervals from each dialysis center.Analysis planThe primary analysis will follow an intent-to-treat approach. The primary outcome will be analyzed at the patient level as the hazard ratio of time-to-first event, estimated from a subdistribution hazards model. Within-center correlation will be accounted for using a robust sandwich estimator. In the primary analysis, patients' observation time will end if they experience the primary outcome, emigrate from Ontario, or die of a noncardiovascular cause (which will be treated as a competing risk event). The between-group difference in the mean drop in intradialytic systolic blood pressure obtained during the dialysis sessions throughout the trial period will be analyzed at the center level using an unadjusted random-effects linear mixed model.Trial statusThe MyTEMP trial period is April 3, 2017, to March 31, 2021. We expect to analyze and report results by 2023 once the updated data are available at ICES.Trial registrationMyTEMP is registered with the US National Institutes of Health at clincaltrials.gov (NCT02628366).Statistical analytic planVersion 1.1 June 15, 2021.

Project description:To effectively navigate a crowded and dynamic visual world, our neurocognitive system possesses the remarkable ability to extract and learn its statistical regularities to implicitly guide the allocation of spatial attention resources in the immediate future. The way through which we deploy attention in the visual space has been consistently outlined by a "center-surround inhibition" pattern, wherein a ring of sustained inhibition is projected around the center of the attentional focus to optimize the signal-noise ratio between goal-relevant targets and interfering distractors. While it has been observed that experience-dependent mechanisms could disrupt the inhibitory ring, whether statistical learning of spatial contingencies has an effect on such a surround inhibition and - if any - through which exact mechanisms it unravels are hitherto unexplored questions. Therefore, in a visual search psychophysical experiment, we aimed to fill this gap by entirely mapping the visuo-spatial attentional profile, asking subjects (N = 26) to detect and report the gap orientation of a 'C' letter appearing either as a color singleton (Baseline Condition) or as a non-salient probe (Probe Condition) - among other irrelevant objects - at progressively increasing probe-to-singleton distances. Critically, we manipulated the color singleton spatial contingency so as to make it appear more frequently adjacent to the probe, specifically at a spatial distance where attending the color singleton generates surround-inhibition on the probe, hindering attentional performance. Results showed that statistical learning markedly reshaped the attentional focus, transforming the center-surround inhibition profile into a non-linear gradient one through a performance gain over the high probability probe-to-singleton distance. Noteworthy, such reshaping was uneven in time and asymmetric, as it varied across blocks and specifically appeared only within manipulated visual quadrants, leaving unaltered the unmanipulated ones. Our findings offer insights of theoretical interest in understanding how environmental regularities orchestrate the way we allocate attention in space through plastic re-weighting of spatial priority maps. Additionally, going beyond the physical dimension, our data provide interesting implications about how visual information is coded within working memory representations, especially under scenarios of heightened uncertainty.

Dataset Information

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

Background

Objective

Methods

Results

Conclusions

Trial registration

Clinicaltrials

Publications

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

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