Statistical analysis plan for the control of blood pressure and risk attenuation-rural Bangladesh, Pakistan, Sri Lanka (COBRA-BPS) trial: a cluster randomized trial for a multicomponent intervention versus usual care in hypertensive patients

Abstract

Background: In rural south Asia, hypertension remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The goal of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) compared to usual care on lowering BP among adults with hypertension in rural south-Asian communities. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness based on clinical and patient-reported endpoints.

Methods/design: The study is a cluster randomized trial which will enroll 2550 participants aged ≥ 40 years with hypertension from rural communities in Bangladesh, Pakistan, and Sri Lanka. The unit of randomization is a cluster defined by 250-300 households. Thirty clusters, 10 from each country, are randomized in a 1:1 ratio to either MCI or usual care, stratified by country and their distance from the clinic. All participants will be assessed every six months over a two-year period after baseline with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits. The primary objective is to assess the effectiveness of MCI as compared with usual care in terms of mean change in systolic BP from baseline to final follow-up at two years. The primary outcome will be modelled using a generalized linear mixed-model for repeated measures based on a participant-level analysis. The model will include cluster random-effects and will use a non-independence residual correlation matrix to account for repeated measures on the same participant. Sensitivity analyses for the primary endpoint will be based on multiple imputation as well as pattern mixture model tipping point analyses. Secondary outcomes will be analyzed using the same modeling approach as for the primary outcome, with appropriate distributions within the exponential family and corresponding link functions.

Discussion: The a priori statistical analysis plan will avoid reporting bias and data-driven analysis for the primary and key secondary outcomes. The results of the study will provide evidence of the benefits and risks of the MCI for BP control in rural communities in south Asian countries with low-resourced public health infrastructure.

Trial registration: Clinicaltrials.gov, NCT02657746 . Registered on 14 January 2016.

Keywords: Blood pressure; Cluster randomized trial; Hypertension; Statistical analysis plan.

Fig. 1

Schematic diagram for cluster selection criteria in the randomization Multicomponent intervention cluster; Usual care cluster; Government clinic nearest to the randomized cluster; Non-randomized cluster; Government clinic outside 10 km radius of randomized cluster. Rectangles represent administrative units. Dotted line surrounding a cluster represents a 10-km radius to the cluster. Dotted line surrounding a government clinic represents a 2-km radium to the clinic. No usual care clusters are within a 10-km radius of MCI clusters. Any usual care cluster should not be nearer to a MCI government clinic than its own; similarly, any MCI cluster should not be nearer to a usual care government clinic than its own

Fig. 2

Statistical power for individual country and overall study at the planned sample size