Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial

NCT02699645 | Completed Phase 3 DMC

• 1 other identifier: TRIDENT-1103886
• Study Type: interventional
• Target: 1,671
• Locations: 10 countries
• Sites: 58

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.

Conditions

Intracerebral Haemorrhage (ICH); Hypertension

Keywords

Blood Pressure (BP); Stroke

Outcome Measures

Primary Outcomes (1)

• Recurrent Stroke

  Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic.

  Average of 6 years

Secondary Outcomes (15)

• Recurrent ICH

  Average of 6 years

• Ischaemic Stroke

  Average of 6 years

• Fatal or disabling stroke

  Average of 6 years

• Mortality

  Average of 6 years

• MACE

  Average of 6 years

Study Arms (2)

Triple Pill (active treatment)

EXPERIMENTAL

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

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

Placebo

PLACEBO COMPARATOR

Matched placebo

Drug: Placebo

Interventions

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

1 pill taken orally once daily for average of 72 months

Also known as: Triple Pill

Triple Pill (active treatment)

Placebo DRUG

1 pill taken orally once daily for average of 72 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The George Institute: lead
• The University of New South Wales: collaborator

Study Sites (58)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Hospital das Clínicas de Botucatu

Botucatu, Brazil

Location

Instituto Flumignano de Medicina

Curitiba, Brazil

Location

Hospital Geral de Fortaleza

Fortaleza, Brazil

Location

Clínica Neurológica e Neurocirurgica de Joinville

Joinville, Brazil

Location

Hospital das Clínicas de Porto Alegre

Porto Alegre, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Brazil

Location

Hospital das Clínicas de Ribeirão Preto

Ribeirão Preto, Brazil

Location

Hospital de Base São José do Rio Preto

Rio Prêto, Brazil

Location

Hospital da Bahia

Salvador, Brazil

Location

Universidade Federal de São Paulo

São Paulo, Brazil

Location

LTD Pineo Medical Ecosystem

Tbilisi, 0112, Georgia

Location

The First University Clinic of Tbilisi State Medical University

Tbilisi, 0141, Georgia

Location

LTD Urgent Neurological Clinic "Neurology"

Tbilisi, 0144, Georgia

Location

LTD S. Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

University Kebangsaan Malaysia Medical Centre

Hulu Langat, Malaysia

Location

Hospital Queen Elizabeth

Kota Kinabalu, Malaysia

Location

Hospital Universiti Sains Malaysia

Kubang Kerian, Malaysia

Location

Sarawak General Hospital

Kuching, Malaysia

Location

Hospital Seberang Jaya

Pulau Pinang, Malaysia

Location

Zuyderland Medical Centre

Heerlen, 6419 PC, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Radboud University Medical Center

Nijmegen, 6525 GC, Netherlands

Location

University College Hospital Ibadan

Ibadan, Nigeria

Location

University of Ilorin

Ilorin, Nigeria

Location

Jos University Teaching Hospital

Jos, Nigeria

Location

Lagos University Teaching Hospital, Lagos

Lagos, Nigeria

Location

Ahmadu Bello University Teaching Hospital

Zaria, Nigeria

Location

National University Hospital

Singapore, Singapore

Location

Kandy Teaching Hospital

Kandy, Kandy, 20000, Sri Lanka

Location

Ragama Teaching Hospital

Ragama, Ragama, 11010, Sri Lanka

Location

Colombo North Teaching Hospital

Colombo, Sri Lanka

Location

Kalubowila (Colombo South) Teaching Hospital

Colombo, Sri Lanka

Location

National Hospital of Sri Lanka

Colombo, Sri Lanka

Location

Karapitiya Teaching Hospital

Galle, Sri Lanka

Location

Gampaha District General Hospital

Gampaha, 11000, Sri Lanka

Location

Jaffna Teaching Hospital

Jaffna, 40000, Sri Lanka

Location

Teaching Hospital Kurunegala

Kurunegala, Sri Lanka

Location

Sri Jayewardenepura General Hospital

Nugegoda, Sri Lanka

Location

Peradeniya Teaching Hospital

Peradeniya, Sri Lanka

Location

Chiayi Chang Gung Memorial Hospital

Chiayi City, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

Location

Royal Infirmary Edinburgh

Edinburgh, EH16 4SB, United Kingdom

Location

Royal Devon & Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Victoria Hospital

Kirkcaldy, KY2 5AH, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, T4 6QG, United Kingdom

Location

Morriston Hospital

Swansea, SA6 6NL, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 34994269 DERIVED

• 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.

  PMID: 34022170 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Hypertension; Stroke

Interventions

Telmisartan; Amlodipine; Indapamide

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Indoles

Study Officials

• Craig Anderson

  The George Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: March 4, 2016
• Study Start: September 28, 2017
• Primary Completion: August 27, 2025
• Study Completion: August 27, 2025
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 2 years after publication of main results
• Access Criteria: Bone fide researchers submit protocol to the Research Office of The George Institute for Global Health

Locations

MY (5); NL (3); BR (10); TW (3); GB (9); NG (5); SR (11); AU (7); SG (1); GE (4)