Clinical trial NCT06352632: ACT-GLOBAL Adaptive Platform Trial for Stroke
Official title: A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stroke
Keywords: Adaptive Platform Trial
Blood Pressure
Tenecteplase
Ischaemic stroke
Intracerebral Haemorrhage
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: University of Calgary
name: Berry Consultants
First posted: 2024-04-08
Enrollment: 20000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Adaptive Platform Trial evaluating multiple interventions in multiple states and domains
Primary purpose: TREATMENT

Brief summary: Stroke is causing 6.6 million deaths and is a major cause of disability worldwide in 2019. There remains an urgent need for interventions that improve outcomes which can be implemented with wide applicability for stroke. ACT-GLOBAL is a multi-factorial, multi-arm, multi-stage, randomised, global adaptive platform trial for stroke, aiming to identify the treatment/s associated with the highest chance of improving outcome in stroke patients. In ACT-GLOBAL multiple questions will be evaluated simultaneously and sequentially as data accrues and can evaluate interactions between different treatment options.

Detailed description: Stroke is the second leading cause of death, worldwide. It is also the second largest cause of disability-adjusted-life-years (DALYs) lost after ischaemic heart disease in developing countries, and third largest contributor to DALYs in developed countries (after ischaemic heart disease, low back and neck pain). In 2019, the absolute numbers of new strokes (12.2 million), stroke-related deaths (6.6 million), and people living with stroke (101.5 million) had increased globally from 1990 (70%, 43%, and 85% increases, respectively).

Steady progress has been made in establishing specific management strategies for patients affected by, or at high-risk of, stroke. Unfortunately, only a few acute treatments have been proven to be beneficial: thrombolysis, endovascular thrombectomy, hemicraniectomy, stroke unit care, and aspirin. There is a continued need for interventions that improve outcomes which can be implemented with wide applicability for stroke.

ACT-GLOBAL is an investigator-initiated, multi-factorial, multi-arm, multi-stage, randomised, global adaptive platform trial for stroke, aiming to find the treatment/s associated with the highest chance of improving outcome after stroke. In ACT-GLOBAL multiple questions will be evaluated simultaneously and sequentially as data accrues and can evaluate interactions between different treatment options.

Frequent adaptive analyses are conducted to assess whether a given intervention is superior, inferior, or equivalent either within a domain or for specific populations within the domain. Where it is anticipated that interactions between interventions in different domains may be likely, the statistical models will allow evaluation of such interactions. Each intervention within a domain with prospectively defined and mutually exclusive strata (sub-groups) of participants will be evaluated within the strata, while information from one stratum may be used (via 'borrowing') to contribute to the analysis of the effect of that intervention in other strata. Specific interventions or subgroups within overall populations may be dropped or cease to enrol, based on pre-specified rules.

The adaptive design allows new interventions or domains or both to be introduced. A Response Adaptive Randomisation algorithm may be used to preferentially randomize participants to interventions that appear to be performing better in domains where applicable.

Unlike traditional trial designs which explicitly prohibit co-enrollment of patients into different trials or multiple therapies, or use a factorial design, the adaptive platform design allows investigators to replicate the real-world environment to estimate possible synergy, competitive interference, or safety profiles of complex treatment protocols.

Eligibility criteria: Platform Inclusion Criteria:

1. Age ≥18 years
2. Clinical diagnosis of stroke

Platform Exclusion Criteria:

There are no platform level exclusion criteria

Each state and domain will specify additional inclusion and exclusion criteria in the respective Domain-Specific Registration. Patients who fulfill the overall platform criteria will be assessed for enrollment into each active domain.

Primary outcomes:
measure: modified Rankin scale (mRS) scores
timeFrame: Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration)
Secondary outcomes:
measure: Excellent functional neurological outcome
timeFrame: Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration)
measure: Independent functional neurological outcome
timeFrame: Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration)
measure: Health Related Quality of Life
timeFrame: Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration)
Other outcomes:
measure: Mortality
timeFrame: Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; State and Domain specific time frame may differ (details will be included in domain-specific registration)
Locations:
city: Sydney
country: Australia
facility: The George Institute for Global Health
state: New South Wales
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: The George Institute
name: Craig Anderson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Bijoy Menon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Michael D Hill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Andrew Demchuk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The George Institute
name: Xiaoying Chen, PhD
role: PRINCIPAL_INVESTIGATOR
References: