SLCTR Registration Number
Date of Registration
The date of last modification
Feb 12, 2018
Scientific Title of Trial
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 acute stroke due to intracerebral hemorrhage.
Public Title of Trial
Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT): Effect of intensive blood pressure lowering treatment provided by a Triple Pill strategy on the time to first occurrence of recurrent stroke in patients with a history of acute stroke due to intracerebral haemorrhage.
Disease of Health Condition(s) Studied
Stroke caused by Intracerebral Hemorrhage (ICH), Hypertension
Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial(TRIDENT)
Universal Trial Number
Any other number(s) assigned to the trial and issuing authority
NCT02699645 (ClinicalTrials.gov), ANZCTR: 12616000327482 (Australian New Zealand Clinical Trials Registry)
What is the research question being addressed?
Can the superiority of a combination of fixed low-dose generic blood pressure lowering agents as a “Triple Pill” strategy on top of standard of care prevent recurrent stroke in patients with a history of ICH and high normal or low-grade hypertension?
Type of study
Randomized controlled trial
Study sites • National Hospital of Sri Lanka • Sri Jayewardenepura General Hospital • Colombo North Teaching Hospital, Ragama • Kurunegala Teaching Hospital • Peradeniya Teaching Hospital
Method of randomization: via a secure web-based internet system. The randomization ratio will be 1:1, and will be stratified to ensure balance in prognostic factors: country of recruitment, age (<65 vs. >65 years) and average of 2 recorded baseline systolic BP measurements (<140 vs >140mmHg).
The double-blind period will be preceded by a single-blind (participants will remain blind), active run-in phase to ensure tolerability and adherence of the regimen. This will last a minimum of 2 weeks and may be extended for a further 2 weeks if the first period was interrupted, problematic or another reason (maximum 4 weeks run-in phase)
All randomized participants will receive study medication for an average of three years.
Interventions Experimental arm: Triple Pill (active treatment) telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg. 1 capsule taken orally once daily for 36 months
Placebo Comparator: Placebo Received via blinded study capsules. 1 capsule taken orally once daily for 36 months
Male and female adults (>18 years) with a history of up to 6 months after symptom onset of primary ICH that is confirmed by imaging (copy of the brain imaging report to be submitted to the Central Coordinating Centre (CCC) labelled with study ID and with personal identifiers removed)
Clinically stable, as judged by investigator
Two resting systolic blood pressure (SBP) levels measured 5 minutes apart in the range 130-160mmHg recorded in a seated position (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
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 1.25 or 2.5mg, or • an equivalent class (ARB, CCB or thiazide-like diuretic), or • a beta-blocker
Contraindication to any of the study medications, in the context of currently prescribed lowering medication
Unlikely/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 not Using adequate birth control
The time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic, assessed by patient and/or clinical report verified by medical documentation of stroke symptoms and imaging.
Primary outcome(s) - Time of assessment(s)
6 monthly from commencement for a total of 3 years
Secondary outcome(s) - Time of assessment(s)
6 monthly from commencement for a total of 3 years
Target number/sample size
500 subjects from Sri Lanka (250 in each arm)
Countries of recruitment
Australia, Japan, Netherlands, Sri Lanka, Taiwan, Province of China, United Kingdom
Anticipated start date
Anticipated end date
State of ethics review approval
Approved by the Ethics Review Committee, Faculty of Medicine, University of Kelaniya on 14 Mar 2017 (P/112/03/2017)
National Health and Medical Research Council (NHMRC) of Australia (Grant number: APP1103886)
Contact person for Scientific Queries/Principal Investigator
Dr Bimsara Senanayake
National Hospital of Sri Lanka Colombo 10
Primary study sponsor/organization
The George Institute for Global Health
The University of Sydney Level 10, King George V Building, 83-117 Missenden Rd Camperdown NSW 2050 Australia
+61 2 8052 4500
+61 2 8052 4501