The TRIDENT trial aims to determine the effectiveness and safety of a single pill combination of three low-dose components (telmisartan 20mg, amlodipine 2.5mg and indapamide 1.25mg) versus placebo on top of standard of care, in patients with a history of stroke due to intracerebral hemorrhage. It is designed as an international, multicenter, double-blind, placebo-controlled, parallel-group, randomized controlled trial. The primary outcome is time from randomization to first occurrence of recurrent stroke, whether intracerebral hemorrhage, ischemic or undifferentiated. This statistical analysis plan pre-specifies the method of analysis for key outcomes and variables collected in the trial. The primary analysis will consist of a Cox proportional hazard adjusted for stratification variables. The analysis plan also includes planned sensitivity analyses including covariate adjustments and subgroup analyses.

AR is seconded part-time to work for George Medicines (GM), which is partly owned by George Health Enterprises (GHE), the social enterprise arm of The George Institute for Global Health (TGI), which holds patents for low-dose fixed-dose combination products for the treatment of hypertension and diabetes; AR is listed as one of the inventors (US 10,369,15; US 10,799,487; US 10,322,117; US 11,033,544). GHE and GM have received funding from public and private investors to conduct the research required for regulatory approval of cardiovascular combination products; AR does not have a financial interest in these patent applications or investments. CA is a consultant for Auzone BioTech China. RB is employed by Veristat. LB and SS report no conflicts of interest.

NCT02699645

This study was funded by The National Health and Medical Research Council (NHMRC) of Australia (Grants 1149987 and 1103886) and PROADI SUS - Ministry of Health of Brazil and Hospital Moinhos de Vento (NUP number 25000.209767/2018-61).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Protocol X16-0082 & 2019/ETH06459 (GI-AU-NMH-2016-01, Version 6.0, Date 6 December 2022): Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial was approved by the Research Ethics and Governance Office of Sydney Local Area Health District, office at the Royal Prince Alfred Hospital, CAMPERDOWN NSW Australia 2050

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the Principal Investigator, Professor Craig Anderson