Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress.

Abstract

BACKGROUND:

Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention.

OBJECTIVES:

The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH.

DESIGN:

An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety.

RESULTS:

Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024.

CONCLUSION:

Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

• Authors: Craig S Anderson, Anthony Rodgers, H Asita de Silva, Sheila Ouriques Martins, Catharina Jm Klijn, Bimsara Senanayake, Ruth Freed, Laurent Billot, Hisatomi Arima, Nguyen Huy Thang, Wan Asyraf Wan Zaidi, Tinatin Kherkheulidze, Kolawole Wahab, Urs Fisher, Tsong-Hai Lee, Christopher Chen, Octavio Pontes-Neto, Thompson Robinson, Jiguang Wang, Sharon Naismith, Lili Song, Floris H Schreuder, Richard I Lindley, Mark Woodward, Stephen MacMahon, Rustam Al-Shahi Salman, Clara K Chow, John Chalmers
• Journal: International journal of stroke : official journal of the International Stroke Society (Int J Stroke) Vol. 17 Issue 10 Pg. 1156-1162 (12 2022) ISSN: 1747-4949 [Electronic] United States
• PMID: 34994269 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents

Topics

• Humans
• Adult
• Stroke
• Cerebral Hemorrhage
• Antihypertensive Agents (therapeutic use)
• Chronic Disease
• Cerebral Infarction