Dataset Information

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

ABSTRACT:

Background

The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor.

Objective

We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database.

Methods

The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses.

Results

The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status.

Conclusions

We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase.

International registered report identifier (irrid)

DERR1-10.2196/36261.

SUBMITTER: Adhikari NK

PROVIDER: S-EPMC9166642 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

Adhikari Neill Kj NK Pinto Ruxandra R Day Andrew G AG Masse Marie-Hélène MH Ménard Julie J Sprague Sheila S Annane Djillali D Arabi Yaseen M YM Battista Marie-Claude MC Cohen Dian D Cook Deborah J DJ Guyatt Gordon H GH Heyland Daren K DK Kanji Salmaan S McGuinness Shay P SP Parke Rachael L RL Tirupakuzhi Vijayaraghavan Bharath Kumar BK Charbonney Emmanuel E Chassé Michaël M Del Sorbo Lorenzo L Kutsogiannis Demetrios James DJ Lauzier François F Leblanc Rémi R Maslove David M DM Mehta Sangeeta S Mekontso Dessap Armand A Mele Tina S TS Rochwerg Bram B Rewa Oleksa G OG Shahin Jason J Twardowski Pawel P Young Paul Jeffrey PJ Lamontagne François F

JMIR research protocols 20220520 5

<h4>Background</h4>The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor.<h4>Objective</h4>We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database.<h4>Methods</h4>The SAP w ...[more]

PMID: 35420994

Similar Datasets

Project description:BackgroundTransforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (< 8 weeks).MethodsThe STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (< 8 weeks): (1) TESI combined with levobupivacaine added to oral pain medication (intervention group 1) versus oral pain medication alone (control group), (2) intervention group 1 versus transforaminal epidural injection with levobupivacaine and saline solution added to oral pain medication (intervention group 2), and (3) intervention group 2 versus control group. Co-primary outcomes were physical functioning (Roland Morris Disability Questionnaire), pain intensity (10-point numerical rating scale), and global perceived recovery (7-point Likert scale, dichotomized into 'recovered' and 'not recovered'). For all three comparisons, we defined the following minimal clinically relevant between-group differences: two points for pain intensity (range 0-10), four points for physical functioning (range 0-24) and a 20% difference in recovery rate. Secondary outcomes are health-related quality of life (EQ-5D-5L) and patient satisfaction (7-point Likert scale) and surgery rate. We also collected resource use data to perform an economic evaluation. Analyses will be conducted by intention-to-treat with p < 0.05 (two-tailed) for all three comparisons. Effects will be estimated using mixed models by maximum likelihood. For each comparison, mean differences, or difference in proportions, between groups will be tested per time point and an overall mean difference, or difference in proportions, between groups during the complete duration of follow-up (6 months) will be estimated. In the economic evaluation, Multivariate Imputation by Chained Equations will be used to handle missing data. Cost and effect differences will be estimated using seemingly unrelated regression, and uncertainty will be estimated using bootstrapping techniques.DiscussionThis statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (< 8 weeks).Trial registrationDutch National trial register NTR4457 (6 March 2014).

Dataset Information

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

Background

Objective

Methods

Results

Conclusions

International registered report identifier (irrid)

Publications

Lessening Organ Dysfunction With Vitamin C (LOVIT) Trial: Statistical Analysis Plan.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets