Design of the asian diabetes outcomes prevention trial: biomarker-guided primary prevention and key protocol updates

Background

Cardiovascular disease is the leading cause of death in type 2 diabetes mellitus (T2D). Early identification of high-risk individuals using biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) provides an opportunity for targeted intensive primary prevention.

Purpose

Among biomarker (NT-proBNP)-identified high-risk T2D patients without pre-existing cardiovascular disease, to test whether intensive preventive therapy reduces cardiovascular events, compared to standard of care.

Methods

Asian Diabetes Outcome Prevention Trial (ADOPT) is a prospective multinational randomized open-label, parallel group, active-controlled, two-arm, long-term morbidity and mortality trial with patients followed for a minimum of 2 years in Singapore, Malaysia, Taiwan, China, India and United Arab Emirates. The target population is adults with T2D and an NT-proBNP >100 pg/mL but without cardiovascular disease (defined as known coronary stenosis > 70%, reduced left ventricular ejection fraction < 40%, or a history of myocardial infarction/coronary revascularization/heart failure hospitalization/stroke/prior non-traumatic lower limb amputation or angioplasty). Patients are randomized to either the (1) Intensive Treatment group (high doses of renin-angiotensin-aldosterone system inhibitor and beta-blocker, as well as preferential use of a sodium-glucose co-transporter 2 inhibitor, on top of standard therapy); or (2) Control group (standard of care). An earlier version of the ADOPT trial design was presented as a poster at the Heart Failure Congress 2019; the current abstract reflects major protocol updates, including revised NT-proBNP eligibility thresholds, early trial termination, and adoption of a hierarchical primary composite endpoint. To improve recruitment feasibility while maintaining population risk, ADOPT lowered the NT-proBNP inclusion threshold from 125 to 100 pg/mL, aligning with emerging evidence that Asians may exhibit heightened cardiovascular risk at lower NT-proBNP levels than Western populations. The ADOPT trial originally began as an event-driven trial in July 2020. Due to funding expiry, recruitment was terminated early in Dec 2024 with 739 randomized patients and followed or 2 years minimally. The primary hierarchical composite endpoint consists of all-cause death, first cardiovascular hospitalization, urgent and elective cardiovascular visits, change in kidney function, change in NT-proBNP at 1 year, HbA1c control (7% threshold) at 2years and blood pressure control (120mmHg and 130mmHg thresholds) at 2years analysed using a win ratio approach.

Significance: No previous cardiovascular outcome trial has tested this intensive primary prevention strategy in a high-risk T2D population identified through biomarkers in a predominantly Asian population. The intensive intervention used in ADOPT may improve patient outcomes, reduce healthcare costs and influence the regional care of patients with T2D.For image description, please refer to the figure legend and surrounding text.