BackgroundThe burden of over 300 million individuals living with hypertension in India is increasing steadily. Most current guidelines recommend initial combination therapy for effective blood pressure (BP) control. However, there is no randomised evidence to inform which combinations to use in South Asian population accounting for over one-quarter of the world’s population. MethodsThis multi-centre, single-blind, randomised, three-arm trial recruited men and women aged 30-79 years with hypertension. The trial compares the efficacy of commonly recommended single pill combinations (SPCs) of three drug classes – calcium channel blocker (amlodipine), ACE inhibitor (perindopril), and a thiazide-like diuretic (indapamide). The primary objective is to determine the most effective two-drug combination, initially at starting doses with forced up-titration at 2 months, in reducing 24-hour ambulatory systolic blood pressure (ASBP) at 6 months. The trial has 85% power to detect a difference of 3mmHg in 24-hour SBP amongst the groups.Participant recruitment took place from August 2022 to February 2024. Baseline resultsThe 1981 participants (42.0% women) enrolled had a mean age of 52.1(SD 11.3) years and a mean BMI of 26.5(SD 4.2) kg/m2. 58.1% and 18.6% of participants were known to have hypertension and diabetes, respectively. The mean ASBP was 135.6 (SD 17.0) mmHg, and the mean ambulatory diastolic blood pressure was 84.5 (SD 10.9) mmHg. ConclusionThe TOPSPIN trial is the first randomised evaluation of commonly used BP-lowering combination therapies in a South Asian population. The results have potentially significant implications for choosing first-line antihypertensive agents among Indians and South Asian diaspora.