To determine the effectiveness of more intensive BP lowering provided by a *Triple Pill* strategy on top of standard of care, on the time to first occurrence of recurrent stroke after ICH.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Vascular haemorrhagic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Primary outcome: Time to first occurrence of recurrent stroke, whether
ischaemic or ICH.
- Secondary outcomes: Recurrent ICH; ischaemic stroke; fatal or disabling
stroke; mortality; MACE [major adverse CV events of CV death, non-fatal
myocardial infarction, or non-fatal stroke]; health-related quality of life
[HRQoL] using the EuroQoL Group 5-Dimension Self-Report Questionnaire [EQ-5D];
physical function (simplified modified Rankin scale [smRS]); cognitive
impairment, defined by standard cut-points on the Montreal Cognitive
Assessments [MoCA].
Secondary outcome
see item primary study parameters/outcome of the study.
Background summary
Intracerebral haemorrhage [ICH] is the most serious and least treatable form of
stroke, accounting for at least 10% of the 20 million new strokes in the world
each year. Survivors are at high risk of recurrent ICH and other serious
cardiovascular [CV] events. Whilst there is strong evidence that this risk can
be reduced by lowering blood pressure [BP], many ICH patients do not receive
any BP lowering treatment, and if they do, receive treatment such that their BP
is inadequately controlled. TRIDENT has been designed to resolve persisting
clinical uncertainty and provide definitive evidence on the effectiveness of
more intensive BP lowering to prevent recurrent serious CV events after ICH
using a simplified combination regimen of BP lowering agents.
Study objective
To determine the effectiveness of more intensive BP lowering provided by a
*Triple Pill* strategy on top of standard of care, on the time to first
occurrence of recurrent stroke after ICH.
Study design
Multicentre, international, double-blinded, placebo-controlled, parallel-group,
randomized controlled trial of a fixed low-dose combination BP lowering pill
(Triple Pill) on top of standard of care, in patients with a history of acute
ICH and systolic BP [SBP] levels defined as at least *high normal to borderline
high* (defined as 130-160 mmHg) and on either minimal or no BP lowering
treatment according to standard guideline definitions.
A 2-week, active run-in phase (in which all participants will receive the
Triple Pill) will precede the double-blind treatment period to ensure the
randomization of patients who tolerate the treatment regimen and procedures,
thus increasing the likelihood of high adherence to the follow-up schedule.
Intervention
All participants who meet the eligibility criteria for the study will be
randomized to:
1. Active treatment: encapsulation of generic regulatory approved combination
of low doses of telmisartan 20mg, amlodipine 2.5mg, and indapamide 1.25mg
(*Triple Pill*), or;
2. Control: encapsulation of 3 placebo tablets.
Study burden and risks
The main risks associated with this trial are (serious) adverse events caused
by antihypertensive drugs (e.g. headache, syncope/collapse, falls, pedal
oedema/ankle swelling, hyperkalaemia, hypokalaemia, hyponatraemia). It is
currently uncertain which of the treatment strategies mentioned above is most
effective and safe. The burden will consist of 5 visits in the first year, with
two follow-up visits yearly thereafter.
Level 10, King George V Building, Missenden Road 83-117
Camperdown NSW 2050
AU
Level 10, King George V Building, Missenden Road 83-117
Camperdown NSW 2050
AU
Listed location countries
Age
Inclusion criteria
1. Adults (>=18 years) with a history stroke due to primary intracerebral
haemorrhage (ICH) confirmed by brain imaging, 2. Clinically stable, as judged
by investigator, 3. Two resting systolic BP (SBP) levels, measured 5 minutes
apart in the range 130-160mmHg recorded in a seated position., 4. Provision of
written informed consent.
Exclusion criteria
1. Taking an ACE inhibitor antihypertensive drug that cannot be switched to any
of the following alternatives:, - telmisartan 20 or 40mg, amlodipine 2.5 or
5mg, indapamide 1.25, or;, - an equivalent class (angiotensin receptor blocker,
calcium channel blocker, or thiazide-like diuretic), or;, - a beta-blocker, 2.
Contraindication to any of the study medications, in the context of currently
prescribed BP lowering medication, 3. Unlikely/unable to complete the study
procedures and/or follow-up, 4. Females of child bearing age and capability,
who are pregnant or breast-feeding, or those not using adequate contraception,
5. Any condition that in the opinion of the responsible physician or
investigator that renders the patient unsuitable for the study (e.g. severe
disability (ie modified Rankin Scale [mRS] score of 4-5] or significant memory
or behavioural disorder or hyperkalaemia and/or hyponatremia, defined by local
lab criteria)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003724-23-NL |
| ClinicalTrials.gov | NCT02699645 |
| CCMO | NL61790.091.17 |