Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial

Summary

An investigator initiated and conducted, multicentre, international, double-blinded, placebo-controlled, parallel-group, randomised controlled trial to determine the effect of more intensive blood pressure control provided by a fixed low-dose combination blood pressure lowering pill ("Triple Pill") strategy on top of standard of care, on time to first occurrence of recurrent stroke in patients with a history of stroke due to intracerebral haemorrhage.

Timeline

Start

2017-09-28

Primary completion

2025-08-27

Completion

2025-08-27

Outcome

Met primary endpoint

paper recurrent stroke had occurred in 38 patients (4.6%) in the triple-pill group and 62 (7.4%) in the placebo group PMID 42019018 ↗

paper (hazard ratio, 0.61; 95% confidence interval [CI], 0.41 to 0.92; P = 0.02) PMID 42019018 ↗

Publications

• Trident Research Group; Anderson CS, Chow CK, de Silva HA, Senanayake B, Wahab K, Al-Shahi Salman R, Klijn CJM, Martins SO, Espinosa N, Kuhles L, Billot L, Arima H, Carcel C, Wang X, Li Q, Shan S, Shanthakumar M, Nguyen HT, Palliyaguruge D, Peiris J, Ranawaka UK, Bandusena S, Rajendiran T, Wijegunasinghe D, Gunasekera H, Wijeweera I, Dissanayake A, Keshavaraj A, Obiako RO, Akinyemi R, Nasi L, Bazan R, Moro CHC, Battaglini M, Zetola V, Law WC, Chia YK, Cordato D, Grimley R, Dahanayaka A, Liyanagamage S, Fernando N, Rasheed NA, Kakabadze N, Beridze M, Aravinthan M, Sahathevan V, Wijesundara D, Ruwanpathirana P, Wan Zaidi WA, Kherkheulidze T, Fischer U, de Souza AC, Lee TH, Chen C, Pontes-Neto O, Robinson T, Wang J, Naismith SL, Barnett M, Delfino C, You S, Liu F, Delcourt C, Moullaali TJ, Wilkinson T, Watson N, Santo K, Han Q, Souza MA, Jolink WMT, Cristofari AB, Zhou Z, Schreuder FH, Lindley RI, Armenis M, Woodward M, Freed R, Song L, Chalmers J, Rodgers A. Three Low-Dose Antihypertensive Agents in a Single Pill after Intracerebral Hemorrhage. N Engl J Med. 2026 Apr 23;394(16):1571-1582. doi: 10.1056/NEJMoa2515043.
• Anderson CS, Rodgers A, de Silva HA, Martins SO, Klijn CJ, Senanayake B, Freed R, Billot L, Arima H, Thang NH, Zaidi WAW, Kherkheulidze T, Wahab K, Fisher U, Lee TH, Chen C, Pontes-Neto O, Robinson T, Wang J, Naismith S, Song L, Schreuder FH, Lindley RI, Woodward M, MacMahon S, Salman RA, Chow CK, Chalmers J. Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress. Int J Stroke. 2022 Dec;17(10):1156-1162. doi: 10.1177/17474930211068671. Epub 2022 Jan 7.
• Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Amlodipine	Other / unclassified	2.5 mg	Oral
Subject	Indapamide	Small molecule	1.25 mg	Oral
Subject	Telmisartan	Other / unclassified	20 mg	Oral

Indications