Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial
- Conditions
- Intracerebral Haemorrhage (ICH)Hypertension
- Interventions
- Registration Number
- NCT02699645
- Lead Sponsor
- The George Institute
- Brief 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.
- Detailed Description
Intracerebral haemorrhage (ICH) is the most serious and least treatable form of stroke, accounting for at least 10% of the 20 million new strokes that occur globally each year. Survivors of ICH are at high risk of recurrent ICH and other serious cardiovascular events.
While there is strong evidence that this risk can be reduced by lowering the blood pressure (BP) of patients after ICH, many patients with ICH do not receive BP-lowering treatment long-term unless BP levels are particularly high, and many do not receive BP combination therapy.
The aim of this study is to assess the safety and efficacy of a combination of fixed low-dose generic BP lowering agents, as a "Triple Pill" strategy on top of standard of care for the prevention of recurrent stroke in patients with a history of ICH and high normal or low grade hypertension. The study is a large-scale, international, double-blind, placebo-controlled, randomised controlled trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1600
- Adults (≥18 years) with a history of primary ICH that is confirmed by imaging (copy of the brain imaging report to be uploaded to the database, labelled with participant identification (ID) and with personal identifiers removed)
- Clinically stable, as judged by investigator
- Average of two resting SBP levels measured 5 minutes apart in the range 130-160mmHg recorded in a seated position (National Heart Foundation of Australia Guidelines). (Patients with higher SBP can be included if considered by attending clinician that management is consistent with local standards of clinical practice)
- Geographical proximity to the recruiting hospital and/or follow-up medical clinic site to allow ready access for in-person clinic visits during follow-up
- No clear contraindication to any of the study treatments
- Provision of written informed consent
-
Taking an ACE-I that cannot be switched to any of the following alternatives:
- telmisartan 20 or 40mg, amlodipine 2.5 or 5mg, indapamide 1.25mg, or
- an equivalent class (ARB, CCB or thiazide [TZ]-like diuretic), or
- a BB
-
Contraindication to any of the study medications, in the context of currently prescribed BP-lowering medication
-
Unable to complete the study procedures and/or follow-up
-
Females of child-bearing age and capability, who are pregnant or breast-feeding, or those of child-bearing age and capability who are not using adequate birth control
-
Significant hyperkalaemia and/or hyponatremia, in the opinion of the responsible physician
-
Estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2
-
Severe hepatic impairment (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3x the upper limit of normal [ULN])
-
Any other condition that in the opinion of the responsible physician or investigator renders the patient unsuitable for the study (e.g. severe disability [i.e. simplified modified Rankin Scale (smRS) of 4-5] or significant memory or behavioural disorder)
Exclusion Criteria for MRI (as applies)
• Any MRI contraindication (e.g. metallic implants, claustrophobia, etc) or participant refusal.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Triple Pill (active treatment) telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg; Placebo Placebo Matched placebo
- Primary Outcome Measures
Name Time Method Recurrent Stroke Average of 6 years Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic.
- Secondary Outcome Measures
Name Time Method Recurrent ICH Average of 6 years Time to first occurrence of recurrent ICH
Ischaemic Stroke Average of 6 years Time to first occurrence of ischaemic stroke
HRQoL according to the EQ-5D-3L Average of 6 years Health-related quality of life according to the European Quality of Life 5-Dimensional Assessment, 3-Level version
Cognitive Impairment Average of 6 years Overall defined by standard cut-points on the Montreal Cognitive Assessment (MoCA)
Depression Average of 6 years According to standard cut-point scores on the PHQ-9
Fatal or disabling stroke Average of 6 years Time to first occurrence of fatal or disabling stroke
Mortality Average of 6 years Mortality
MACE Average of 6 years Major adverse cardiovascular events - CV death, non-fatal MI or non-fatal stroke
Physical function Average of 6 years Physical function as assessed by smRS
Change in SBP Average of 6 years Change in SBP
Cognitive Impairment Supplement Average of 6 years Overall defined by standard cut-points with Brief Memory and Executive Test (BMET) together with assessments of functional impairment related to cognition defined by QDRS score and short form IQCODE, which will also allow subtyping of 'probable' or 'definite' dementia or mild cognitive impairment according to standard diagnostic criteria.
Cerebral small vessel disease Average of 6 years Defined by various standard markers on routine MRI, measured by individual components and overall CSVD burden. The primary measure of CSVD is FLAIR WMH volume.
Medication Adherence Average of 6 years Self-reported measures, pill counts
Safety in terms of Serious Adverse Events (SAEs) Average of 6 years SAEs
Tolerability in terms of Adverse Events of Special Interest (AESIs) Average of 6 years AESIs: Headache, Syncope/collapse, Falls, Pedal oedema/ankle swelling, Hypo/hyperkalaemia, Hyponatraemia
Trial Locations
- Locations (65)
Zuyderland Medical Centre
🇳🇱Heerlen, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Netherlands
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Royal Prince Alfred Hospital
🇦🇺Sydney, New South Wales, Australia
LTD Pineo Medical Ecosystem
🇬🇪Tbilisi, Georgia
Kalubowila (Colombo South) Teaching Hospital
🇱🇰Colombo, Sri Lanka
Hospital Universiti Sains Malaysia
🇲🇾Kubang Kerian, Malaysia
Karapitiya Teaching Hospital
🇱🇰Galle, Sri Lanka
Keelung Chang Gung Memorial Hospital
🇨🇳Keelung, Taiwan
The First University Clinic of Tbilisi State Medical University
🇬🇪Tbilisi, Georgia
National Hospital of Sri Lanka
🇱🇰Colombo, Sri Lanka
Kandy Teaching Hospital
🇱🇰Kandy, Sri Lanka
Peradeniya Teaching Hospital
🇱🇰Peradeniya, Sri Lanka
LTD Urgent Neurological Clinic "Neurology"
🇬🇪Tbilisi, Georgia
Hospital Seberang Jaya
🇲🇾Pulau Pinang, Malaysia
University College Hospital Ibadan
🇳🇬Ibadan, Nigeria
Colombo North Teaching Hospital
🇱🇰Colombo, Sri Lanka
Jaffna Teaching Hospital
🇱🇰Jaffna, Sri Lanka
Ragama Teaching Hospital
🇱🇰Ragama, Sri Lanka
Chiayi Chang Gung Memorial Hospital
🇨🇳Chiayi City, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Irmandade da Santa Casa de Misericórdia de Matão
🇧🇷São Paulo, Brazil
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Port Macquarie Base Hospital
🇦🇺Port Macquarie, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Instituto Flumignano de Medicina
🇧🇷Curitiba, Brazil
Hospital Geral de Fortaleza
🇧🇷Fortaleza, Brazil
Clínica Neurológica e Neurocirurgica de Joinville
🇧🇷Joinville, Brazil
Hospital das Clínicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Universidade Federal de São Paulo
🇧🇷São Paulo, Brazil
Hospital de Base São José do Rio Preto
🇧🇷Rio Prêto, Brazil
Hospital das Clínicas de Ribeirão Preto
🇧🇷Ribeirão Preto, Brazil
Hospital da Bahia
🇧🇷Salvador, Brazil
LTD S. Khechinashvili University Hospital
🇬🇪Tbilisi, Georgia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
Rijnstate Hospital
🇳🇱Arnhem, Netherlands
National University Hospital
🇸🇬Singapore, Singapore
Gampaha District General Hospital
🇱🇰Gampaha, Sri Lanka
Sri Jayewardenepura General Hospital
🇱🇰Nugegoda, Sri Lanka
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Royal Infirmary Edinburgh
🇬🇧Edinburgh, United Kingdom
Victoria Hospital
🇬🇧Kirkcaldy, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
Morriston Hospital
🇬🇧Swansea, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Military Central Hospital 108
🇻🇳Hanoi, Vietnam
Hospital das Clínicas de Botucatu
🇧🇷Botucatu, Brazil
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Brazil
University Kebangsaan Malaysia Medical Centre
🇲🇾Hulu Langat, Malaysia
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Malaysia
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
University Medical Centre, Utrecht
🇳🇱Utrecht, Netherlands
University of Ilorin
🇳🇬Ilorin, Nigeria
Lagos University Teaching Hospital, Lagos
🇳🇬Lagos, Nigeria
Jos University Teaching Hospital
🇳🇬Jos, Nigeria
Teaching Hospital Kurunegala
🇱🇰Kurunegala, Sri Lanka
University Hospital Zurich
🇨🇭Zürich, Switzerland
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Royal Devon & Exeter Hospital
🇬🇧Exeter, United Kingdom
Ahmadu Bello University Teaching Hospital
🇳🇬Zaria, Nigeria