Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis

BACKGROUND: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis. OBJECTIVE: To describe a statistical analysis plan for the BLING III study. METHODS: The statistical analysis plan was designed by the trial statistician and chief investigators and approved by the BLING III management committee before the completion of data collection. Statistical analyses for primary, secondary and tertiary outcomes and planned subgroup analyses are described in detail. Interim analysis by the Data Safety and Monitoring Committee (DSMC) has been conducted in accordance with a pre-specified DSMC charter. RESULTS AND CONCLUSIONS: The statistical analysis plan for the BLING III study is published before completion of data collection and unblinding to minimise analysis bias and facilitate public access and transparent analysis and reporting of study findings. TRIAL REGISTRATION: ClinicalTrials.gov Registry NCT03212990.

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Faculty Opinions recommendation of Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1160807.628059 ◽

2009 ◽

Author(s):

Babak Sarani

Keyword(s):

Randomised Controlled Trial ◽

Occupational Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Controlled Trial ◽

Mechanically Ventilated ◽

Randomised Controlled

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Faculty Opinions recommendation of A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomised controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718006609.793477846 ◽

2013 ◽

Author(s):

David Kuter ◽

Rachel Rosovsky

Keyword(s):

Randomised Controlled Trial ◽

Comparative Study ◽

Critically Ill ◽

Critically Ill Patients ◽

Controlled Trial ◽

Randomised Controlled ◽

Double Blinded

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Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-016-1331-3 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 27

Author(s):

Mette Krag ◽

◽

Anders Perner ◽

Jørn Wetterslev ◽

Matt P. Wise ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Proton Pump Inhibitor ◽

Critically Ill ◽

Proton Pump ◽

Study Protocol ◽

Critically Ill Patients ◽

Stress Ulcer ◽

Controlled Trial ◽

Ulcer Prophylaxis ◽

Randomised Controlled

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Evaluating probiotics for the prevention of ventilator-associated pneumonia: a randomised placebo-controlled multicentre trial protocol and statistical analysis plan for PROSPECT

BMJ Open ◽

10.1136/bmjopen-2018-025228 ◽

2019 ◽

Vol 9 (6) ◽

pp. e025228 ◽

Cited By ~ 6

Author(s):

Jennie Johnstone ◽

Diane Heels-Ansdell ◽

Lehana Thabane ◽

Maureen Meade ◽

John Marshall ◽

...

Keyword(s):

Statistical Analysis ◽

Critically Ill ◽

Critically Ill Patients ◽

Controlled Trial ◽

Statistical Analysis Plan ◽

Hospital Length Of Stay ◽

Sensitivity Analyses ◽

Ventilator Associated Pneumonia ◽

Increased Risk ◽

The Impact

IntroductionVentilator-associated pneumonia (VAP) is the most common healthcare-associated infection in critically ill patients. Prior studies suggest that probiotics may reduce VAP and other infections in critically ill patients; however, most previous randomised trials were small, single centre studies. The Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) aims to determine the impact of the probioticLactobacillus rhamnosusGG on VAP and other clinically important outcomes in critically ill adults.MethodsPROSPECT is a multicentre, concealed, randomised, stratified, blinded, controlled trial in patients ≥18 years old, anticipated to be mechanically ventilated ≥72 hours, in intensive care units (ICUs) in Canada, the USA and Saudi Arabia. Patients receive either 1×1010 colony forming units ofL. rhamnosusGG twice daily or an identical appearing placebo. Those at increased risk of probiotic infection are excluded. The primary outcome is VAP. Secondary outcomes are other ICU-acquired infections includingClostridioides difficileinfection, diarrhoea (including antibiotic-associated diarrhoea), antimicrobial use, ICU and hospital length of stay and mortality. The planned sample size of 2650 patients is based on an estimated 15% VAP rate and will provide 80% power to detect a 25% relative risk reduction.Ethics and disseminationThis protocol and statistical analysis plan outlines the methodology, primary and secondary analyses, sensitivity analyses and subgroup analyses. PROSPECT is approved by Health Canada (#9427-M1133-45C), the research ethics boards of all participating hospitals and Public Health Ontario. Results will be disseminated via academic channels (peer reviewed journal publications, professional healthcare fora including international conferences) and conventional and social media. The results of PROSPECT will inform practice guidelines worldwide.Trialregistration numberNCT02462590; Pre-results.

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