Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201907745723209 Date of Approval: 22/07/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT)
Official scientific title 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 (TRIDENT).
Brief summary describing the background and objectives of the trial Acute 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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TRIDENT
Disease(s) or condition(s) being studied Acute Intracerebral Haemorrhage, Hypertension
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 23/09/2019
Actual trial start date 06/12/2019
Anticipated date of last follow up 30/06/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 1500
Actual target sample size (number of participants) 1606
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Triple Pill Telmisartan 20mg, Amlodipine 2.5mg, and Indapamide 1.25mg 1 pill taken orally once daily for an average of 36 months Triple Pill (active treatment) - telmisartan 20mg, amlodipine 2.5mg and indapamide 1.25mg; taken orally, once daily for 36 months. Medication adherence and accountability is monitored through self-reports of doses missed and pill counts at every visit until end of treatment (Visits 3-9) 750
Control Group Placebo 1 pill 1 capsule taken orally once daily for an average of 36 months Placebo - commonly used excipients (to be determined) received via blinded study capsules 750 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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. (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: o telmisartan 20 or 40mg, amlodipine 2.5 or 5mg, indapamide 1.25 or 2.5mg, or o an equivalent class (ARB, CCB or thiazide-like diuretic), or o a beta-blocker • 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) <30 mL/min/1.73m2 • Severe hepatic impairment (ALT or AST >3x the upper limit of normal [ULN]) Any other conditions that in the opinion of the responsible physician or investigator that renders the patient unsuitable for the study (e.g. severe disability [i.e. smRS of 4-5] or significant memory or behavioural disorder) 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 19/06/2019 National Health Research Ethics Committee of Nigeria
Ethics Committee Address
Street address City Postal code Country
Federal Ministry of Health, Federal Secretariat Complex Shehu Shagari Way, Garki, Abuja P.M.B. 083, Garki-Abuja Abuja 00001 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Recurrent ICH, assessed by patient and/or clinical report verified by medical documentation of stroke symptoms and imaging Reviewed 6-monthly, patient follow up,3 years
Secondary Outcome Ischaemic Stroke, assessed by patient and/or clinical report verified by medical documentation of stroke symptoms and imaging Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Fatal or disabling stroke, assessed by patient and/or clinical report verified by medical documentation of stroke symptoms and imaging. Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Mortality, assessed by review of medical records Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Occurrence of MACE (major adverse CV events - CV death, non-fatal myocardial infarction, or non-fatal stroke), assessed by patient report verified by medical records and investigations Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Physical function assessed by Modified Rankin Scale (mRS) assessed during follow up clinic visits Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Change in systolic blood pressure (BP) assessed by sphygmomanometer during follow up clinic visits Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Health-related Quality of Life (HRQoL) according to the EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D) assessed during follow up clinic visits Reviewed 6-monthly, patient follow up,3 years
Secondary Outcome Clinically significant cognitive impairment, overall defined by standard cut-points on the Montreal Cognitive Assessment (MoCA), and supplemented with the Brief Memory & Executive Test (BMET) Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Medical adherence assessed by self-reported measures and pill counts. Reviewed 6-monthly, patient follow up,3 years
Secondary Outcome Depression, according to standard cut-point scores on the PHQ-9. Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome Cerebral small vessel disease 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. Reviewed 6-monthly, patient follow up, 3 years
Secondary Outcome safety (serious adverse events [SAEs]); and tolerability (adverse events of special interest [AESI]) Reviewed 6-monthly, patient follow up, 3 years
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Ilorin P.M.B. 1515 Ilorin 240003 Nigeria
Ahmadu Bello University Teaching Hospital Samaru zaria 810001 Nigeria
Jos University Teaching Hospital P.M.B. 2076 Jos 930001 Nigeria
Lagos University Teaching Hospital Ishaga Road Lagos 00001 Nigeria
University College Hospital Ibadan Queen Elizabeth Road, Ibadan 00001 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
National Health and Medical Research Council Level 1, 16 Marcus Clarke Street Canberra ACT 2601 Australia
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor The George Institute for Global Health Level 18, International Towers 3, 300 Barangaroo Ave, Barangaroo NSW 2000 Barangaroo 2000 Australia Health and Medical Research Institute
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kolawole Wahab wahab.bw@unilorin.edu.ng 08033800873 University of Ilorin Teaching Hospital
City Postal code Country Position/Affiliation
Ilorin Nigeria Principal Investigator University of Ilorin Teaching Hospital Regional Coordinating Center
Role Name Email Phone Street address
Scientific Enquiries Craig Anderson canderson@georgeinstitute.org.au +61299934521 The George Institute for Global Health, Australia Level 18, International Towers 3, 300 Barangaroo Ave, Barangaroo NSW 2000, Barangaroo, Australia
City Postal code Country Position/Affiliation
Barangaroo NSW 2000 Australia Principal Investigator The George Institute
Role Name Email Phone Street address
Public Enquiries Adebukunola Telufusi info@xceneresearch.com +2348149906684 15 Ogundana Street, Off Allen Avenue
City Postal code Country Position/Affiliation
Lagos 000001 Nigeria Executive Director CRO Xcene Research
Role Name Email Phone Street address
Public Enquiries Ruth Freed rfreed@georgeinstitute.org.au +61299934522 The George Institute for Global Health, Australia Level 18, International Towers 3, 300 Barangaroo Ave, Barangaroo NSW 2000, Barangaroo, Australia
City Postal code Country Position/Affiliation
Barangaroo NSW 2000 Australia Senior Project Manager The George Institute for Global Health
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The intention is to publish the results in aggregate in a peer reviewed journal within 12 months of completion and not to share IPD. Clinical Study Report The IDP information will not be shared The IDP information will not be shared
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information