Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial

Hypertension Clinical Trial

— TRIDENT  

Official title:

Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT), Substudies: MRI, Cognitive

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02699645
• Other study ID #: TRIDENT-1103886
• Status: Recruiting
• Phase: Phase 3
• Start date: September 28, 2017
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: The George Institute
• Contact: Natalie Espinosa
• Phone: +61 2 8052 4561
• Email: nespinosa[@]georgeinstitute.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1600
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Exclusion Criteria for MRI (as applies)

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

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Hypertension
• Intracerebral Haemorrhage (ICH)

Intervention

Drug:
• telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg
1 pill taken orally once daily for average of 72 months
• Placebo
1 pill taken orally once daily for average of 72 months

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	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	Irmandade da Santa Casa de Misericórdia de Matão	São Paulo
Brazil	Universidade Federal de São Paulo	São Paulo
Georgia	LTD Pineo Medical Ecosystem	Tbilisi
Georgia	LTD S. Khechinashvili University Hospital	Tbilisi
Georgia	LTD Urgent Neurological Clinic "Neurology"	Tbilisi
Georgia	The First University Clinic of Tbilisi State Medical University	Tbilisi
Malaysia	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
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Rijnstate Hospital	Arnhem
Netherlands	Zuyderland Medical Centre	Heerlen
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	University Medical Centre, Utrecht	Utrecht
Nigeria	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
Singapore	National University Hospital	Singapore
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	Kandy Teaching Hospital	Kandy
Sri Lanka	Teaching Hospital Kurunegala	Kurunegala
Sri Lanka	Sri Jayewardenepura General Hospital	Nugegoda
Sri Lanka	Peradeniya Teaching Hospital	Peradeniya
Sri Lanka	Ragama Teaching Hospital	Ragama
Switzerland	University Hospital Zurich	Zürich
Taiwan	Chiayi Chang Gung Memorial Hospital	Chiayi City
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Keelung Chang Gung Memorial Hospital	Keelung
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
United Kingdom	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
Vietnam	Military Central Hospital 108	Hanoi

Sponsors (2)

Lead Sponsor	Collaborator
The George Institute	The University of New South Wales

Countries where clinical trial is conducted

Australia,  Brazil,  Georgia,  Malaysia,  Netherlands,  Nigeria,  Singapore,  Sri Lanka,  Switzerland,  Taiwan,  United Kingdom,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrent Stroke	Time to first occurrence of recurrent stroke, whether ischaemic or haemorrhagic.	Average of 6 years
Secondary	Recurrent ICH	Time to first occurrence of recurrent ICH	Average of 6 years
Secondary	Ischaemic Stroke	Time to first occurrence of ischaemic stroke	Average of 6 years
Secondary	Fatal or disabling stroke	Time to first occurrence of fatal or disabling stroke	Average of 6 years
Secondary	Mortality	Mortality	Average of 6 years
Secondary	MACE	Major adverse cardiovascular events - CV death, non-fatal MI or non-fatal stroke	Average of 6 years
Secondary	Physical function	Physical function as assessed by smRS	Average of 6 years
Secondary	Change in SBP	Change in SBP	Average of 6 years
Secondary	HRQoL according to the EQ-5D-3L	Health-related quality of life according to the European Quality of Life 5-Dimensional Assessment, 3-Level version	Average of 6 years
Secondary	Cognitive Impairment	Overall defined by standard cut-points on the Montreal Cognitive Assessment (MoCA)	Average of 6 years
Secondary	Cognitive Impairment Supplement	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.	Average of 6 years
Secondary	Depression	According to standard cut-point scores on the PHQ-9	Average of 6 years
Secondary	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.	Average of 6 years
Secondary	Medication Adherence	Self-reported measures, pill counts	Average of 6 years
Secondary	Safety in terms of Serious Adverse Events (SAEs)	SAEs	Average of 6 years
Secondary	Tolerability in terms of Adverse Events of Special Interest (AESIs)	AESIs: Headache, Syncope/collapse, Falls, Pedal oedema/ankle swelling, Hypo/hyperkalaemia, Hyponatraemia	Average of 6 years