Effectiveness and safety of a New Standardised TrEatment Protocol based on initial/early therapy with single-pill combinations of blood pressure-lowering drugs for improving blood pressure control (NewSTeP): Rationale, design of a randomized clinical trial and baseline characteristics of the trial participants (Preprint)

BACKGROUND Hypertension is the leading modifiable risk factor for cardiovascular disease (CVD). Despite availability of blood pressure (BP)-lowering therapies, BP control rates remain suboptimal. Reluctance to initiate treatment with combination therapy and delayed treatment intensification contribute to poor control. Early use of single-pill combinations (SPCs) within standardised treatment protocols (STPs) may improve outcomes, but evidence from India is limited. OBJECTIVE To evaluate the effectiveness and safety of a new STP incorporating initial or early use of SPCs compared with usual care among adults with hypertension. METHODS The New Standardised TrEatment Protocol (NewSTeP) trial is a pragmatic, multicentre, randomized, parallel-group, open-label trial conducted in tertiary healthcare centres in India. Adults with hypertension who are untreated or receiving one BP-lowering drug and require treatment initiation or intensification (n = 300) will be randomized 1:1 to either a new STP incorporating early SPC therapy or usual care. Participants will be followed for 6 months. The primary effectiveness outcome is change in home-measured mean systolic BP from randomization to month 6. The primary safety outcome is discontinuation of trial drug due to adverse events. Secondary outcomes include proportion of participants achieving BP control, change in diastolic BP, incidence of adverse events of special interest, treatment adherence, treatment modification, and time to BP control. A process evaluation will assess reach, implementation, acceptability, and sustainability, while an economic evaluation will assess cost-effectiveness. RESULTS Between October 2025 and March 2026, 300 participants were randomized across nine sites (150 to New STP; 150 usual care) from 360 screened individuals. Final follow-up is expected in September 2026, with results anticipated in October 2026. CONCLUSIONS The NewSTeP trial will provide evidence on the effectiveness, safety, implementation, and cost-effectiveness of an SPC-based STP for hypertension management in India and inform future hypertension control strategies and policies. CLINICALTRIAL The trial is registered with the Clinical Trials Registry–India (CTRI/2025/07/091649).