ACT-GLOBAL Adaptive Platform Trial for Stroke

T

The George Institute

Status and phase

Not yet enrolling
Phase 3

Conditions

Stroke

Treatments

Drug: Low-dose intravenous tenecteplase
Other: Moderate Blood Pressure Control
Other: No intravenous tenecteplase
Other: Intensive Blood Pressure Control
Drug: Standard-dose intravenous tenecteplase
Other: Placebo
Drug: NoNO-42
Other: Conservative Blood Pressure Control

Study type

Interventional

Funder types

Other

Identifiers

NCT06352632
ACT-GLOBAL_Master

Details and patient eligibility

About

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.

Full 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.

Enrollment

20,000 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

Single Blind

20,000 participants in 3 patient groups

IV thrombolysis domain
Experimental group
Description:
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to optimize the use of intravenous Tenecteplase in participants with Acute Ischemic Stroke.
Treatment:
Drug: Standard-dose intravenous tenecteplase
Other: No intravenous tenecteplase
Drug: Low-dose intravenous tenecteplase
Blood Pressure domain
Experimental group
Description:
Third Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED3/MT) as a domain of ACT-GLOBAL to compare three BP lowering management strategies, that of conservative, moderate and intensive BP lowering in patients with Acute Ischaemic Stroke admitted to participating hospitals who has an elevated SBP after reperfusion therapy via Endovascular Thrombectomy, and reliably determine, which approach leads to improved functional outcome. Locally available and approved i.v. BP lowering agents can be used in this domain.
Treatment:
Other: Conservative Blood Pressure Control
Other: Intensive Blood Pressure Control
Other: Moderate Blood Pressure Control
ACT-42 domain
Experimental group
Description:
This domain has a Phase 2b, multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive design and aim to determine the efficacy and safety of NoNO-42 in participants with Acute Ischaemic Stroke selected for thrombolysis with or without Endovascular Thrombectomy.
Treatment:
Drug: NoNO-42
Other: Placebo

Trial contacts and locations

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Central trial contact

Xiaoying Chen, PhD; Bijoy Menon, MD, PhD

Data sourced from clinicaltrials.gov

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