Efficacy of propofol-supplemented cardioplegia on biomarkers of organ injury in patients having cardiac surgery using cardiopulmonary bypass: a Statistical Analysis Plan for the ProMPT-2 randomised controlled trial.

Abstract

Background The ProMPT-2 trial (Propofol for Myocardial Protection Trial #2) aims to compare the safety and efficacy of low and high dose propofol supplementation of the cardioplegia solution during adult cardiac surgery versus sham supplementation. This update presents the statistical analysis plan, detailing how the trial data will be analysed and presented. Outlined analyses are in line with the Consolidated Standards of Reporting Trials and the statistical analysis plan has been written prior to database lock and the final analysis of trial data to avoid reporting bias (following recommendations from the International Conference on Harmonisation of Good Clinical Practice). Methods/design ProMPT-2 is a multi-centre, blinded, parallel three-group randomised controlled trial aiming to recruit 240 participants from UK cardiac surgery centres to either sham cardioplegia supplementation, low dose (6µg/ml) or high dose (12µg/ml) propofol cardioplegia supplementation. The primary outcome is cardiac-specific troponin T levels (a biomarker of cardiac injury) measured during the first 48h following surgery. The statistical analysis plan describes the planned analyses of the trial primary and secondary outcomes in detail, including approaches to deal with: missing data, multiple testing, violation of model assumptions, withdrawals from the trial, non-adherence with the treatment and other protocol deviations. It also outlines the planned sensitivity analyses and exploratory analyses to be performed. Discussion This manuscript prospectively describes, prior to the completion of data collection and database lock, the analyses to be undertaken for the ProMPT-2 trial to reduce risk of reporting and data-driven analyses. Trial registration: ISRCTN, ISRCTN15255199. Registered 26th March 2019, https://www.isrctn.com/ISRCTNISRCTN15255199