Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial

NCT ID: NCT02699645

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1671 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2025-08-27

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.

Conditions

Intracerebral Haemorrhage (ICH); Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Triple Pill (active treatment)

telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg;

Group Type: EXPERIMENTAL

telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg

Intervention Type: DRUG

1 pill taken orally once daily for average of 72 months

Placebo

Matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1 pill taken orally once daily for average of 72 months

Interventions

telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg

1 pill taken orally once daily for average of 72 months

Intervention Type: DRUG

Placebo

1 pill taken orally once daily for average of 72 months

Intervention Type: DRUG

Other Intervention Names

Triple Pill

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Any MRI contraindication (e.g. metallic implants, claustrophobia, etc) or participant refusal.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of New South Wales

OTHER

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Anderson

Role: PRINCIPAL_INVESTIGATOR

The George Institute

Locations

Liverpool Hospital

Liverpool, New South Wales, Australia

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Hospital das Clínicas de Botucatu

Botucatu, , Brazil

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

Hospital Moinhos de Vento

Porto Alegre, , Brazil

Hospital das Clínicas de Ribeirão Preto

Ribeirão Preto, , Brazil

Hospital de Base São José do Rio Preto

Rio Prêto, , Brazil

Hospital da Bahia

Salvador, , Brazil

Universidade Federal de São Paulo

São Paulo, , Brazil

LTD Pineo Medical Ecosystem

Tbilisi, , Georgia

The First University Clinic of Tbilisi State Medical University

Tbilisi, , Georgia

LTD Urgent Neurological Clinic "Neurology"

Tbilisi, , Georgia

LTD S. Khechinashvili University Hospital

Tbilisi, , Georgia

University Kebangsaan Malaysia Medical Centre

Hulu Langat, , Malaysia

Hospital Queen Elizabeth

Kota Kinabalu, , Malaysia

Hospital Universiti Sains Malaysia

Kubang Kerian, , Malaysia

Sarawak General Hospital

Kuching, , Malaysia

Hospital Seberang Jaya

Pulau Pinang, , Malaysia

Zuyderland Medical Centre

Heerlen, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Radboud University Medical Center

Nijmegen, , Netherlands

University College Hospital Ibadan

Ibadan, , Nigeria

University of Ilorin

Ilorin, , Nigeria

Jos University Teaching Hospital

Jos, , Nigeria

Lagos University Teaching Hospital, Lagos

Lagos, , Nigeria

Ahmadu Bello University Teaching Hospital

Zaria, , Nigeria

National University Hospital

Singapore, , Singapore

Kandy Teaching Hospital

Kandy, Kandy, Sri Lanka

Ragama Teaching Hospital

Ragama, Ragama, Sri Lanka

Colombo North Teaching Hospital

Colombo, , Sri Lanka

Kalubowila (Colombo South) Teaching Hospital

Colombo, , Sri Lanka

National Hospital of Sri Lanka

Colombo, , Sri Lanka

Karapitiya Teaching Hospital

Galle, , Sri Lanka

Gampaha District General Hospital

Gampaha, , Sri Lanka

Jaffna Teaching Hospital

Jaffna, , Sri Lanka

Teaching Hospital Kurunegala

Kurunegala, , Sri Lanka

Sri Jayewardenepura General Hospital

Nugegoda, , Sri Lanka

Peradeniya Teaching Hospital

Peradeniya, , Sri Lanka

Chiayi Chang Gung Memorial Hospital

Chiayi City, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Linkou Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Royal Infirmary Edinburgh

Edinburgh, , United Kingdom

Royal Devon & Exeter Hospital

Exeter, , United Kingdom

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Victoria Hospital

Kirkcaldy, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Salford Royal Hospital

Salford, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Morriston Hospital

Swansea, , United Kingdom

Countries

Australia; Brazil; Georgia; Malaysia; Netherlands; Nigeria; Singapore; Sri Lanka; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34994269 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34022170 (View on PubMed)

Other Identifiers

TRIDENT-1103886

Identifier Type: -

Identifier Source: org_study_id