Craig S Anderson1,2,3,4, Anthony Rodgers1, H Asita de Silva5,6, Sheila Ouriques Martins7,8, Catharina Jm Klijn9, Bimsara Senanayake10, Ruth Freed1, Laurent Billot1,11,12, Hisatomi Arima13, Nguyen Huy Thang14, Wan Asyraf Wan Zaidi15, Tinatin Kherkheulidze16, Kolawole Wahab17, Urs Fischer18,19, Tsong-Hai Lee20,21, Christopher Chen22, Octavio Pontes-Neto23, Thompson Robinson24, Jiguang Wang25, Sharon Naismith26, Lili Song1,2, Floris H Schreuder9, Richard I Lindley1,27, Mark Woodward1,11, Stephen MacMahon1,11, Rustam Al-Shahi Salman28, Clara K Chow1,27, John Chalmers1. 1. The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. 2. The George Institute China at Peking University Health Sciences Center, Beijing, China. 3. Heart Health Research Center, Beijing, China. 4. Neurology Department, Royal Prince Alfred Hospital, Sydney, NSW, Australia. 5. Clinical Trials Unit, Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka. 6. Institute of Neurology, National Hospital of Sri Lanka, Colombo, Sri Lanka. 7. Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. 8. Neurology Service, Hospital Moinhos de Vento, Porto Alegre, Brazil. 9. Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. 10. Neurology Department, National Hospital of Sri Lanka, Colombo, Sri Lanka. 11. The George Institute for Global Health, School of Public Health, Imperial College London, London, UK. 12. University of Bordeaux, Bordeaux, France. 13. Department of Preventive Medicine and Public Health, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. 14. Stroke Unit, 115 Hospital, Ho Chi Minh City, Vietnam. 15. Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia. 16. Department of Neurology, Tbilisi State Medical University, Tbilisi, GA, USA. 17. Department of Medicine, University of Ilorin, Ilorin, Nigeria. 18. Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland. 19. Department of Neurology, University Hospital Basel, Basel, Switzerland. 20. Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, UK. 21. College of Medicine, Chang Gung University, Taoyuan, UK. 22. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 23. Department of Neurosciences and Behavioural Sciences, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil. 24. College of Life Sciences and NIHR Biomedical Research Centre, University of Leicester, Leicester, UK. 25. Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 26. Faculty of Science, Charles Perkins Centre and Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. 27. Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW, Australia. 28. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
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.
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.