Digoxin in rheumatic heart disease - Rationale and design of a multi-centre, placebo controlled double blind randomised controlled trial (Dig-RHD trial).

Background: Rheumatic heart disease (RHD), is a public health problem in low and middle-income countries. It causes high morbidity and mortality due to heart failure (HF), but there are no randomised trials of HF-treatments in these patients. Digoxin is an inexpensive drug that is widely used in RHD despite a lack of data on its effect on clinical outcomes. The Digoxin in RHD (Dig-RHD) trial will evaluate the impact of the drug on clinical outcomes in patients with RHD.

Methods: The Dig-RHD trial is an investigator-initiated multi-centre, pragmatic, randomized placebo-controlled, parallel-arm, superiority trial. Symptomatic adult patients with RHD were randomized to receive oral digoxin or matching placebo on a background of usual care. The primary outcome is a composite of all-cause death, new-onset or worsening HF. Key secondary outcomes are, all-cause death, HF-related death, hospitalization for HF, sudden death, and self-reported quality of life. Patients were enrolled at 12 academic medical centres in India, beginning in February 2022. Enrolment of 1769 patients was completed in August 2024. One interim review of the data by the independent Data Safety Monitoring Board, after half the primary outcome events had accrued, indicated no safety signals. The last follow-up visits are scheduled to complete in December 2025.

Conclusion: Dig-RHD is the first randomized trial of digoxin in RHD powered for clinical outcomes, and the results will have major implications for the routine management of patients with RHD. (Clinical trial registration: CTRI/2021/04/032858).