ACT-GLOBAL Adaptive Platform Trial for Stroke

Stroke Clinical Trial

Official title:

A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06352632
• Other study ID #: ACT-GLOBAL_Master
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 2024
• Est. completion date: May 2034

Study information

• Verified date: May 2024
• Source: The George Institute
• Contact: Xiaoying Chen, PhD
• Phone: +61280524549
• Email: xchen[@]georgeinstitute.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20000
• Est. completion date: May 2034
• Est. primary completion date: May 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Standard-dose intravenous tenecteplase
Standard-dose intravenous tenecteplase (0.25 mg/kg body weight); one-time IV bolus injection soon after randomisation
• Low-dose intravenous tenecteplase
Low-dose intravenous tenecteplase (0.18 mg/kg body weight); one-time IV bolus injection soon after randomisation

Other:
• No intravenous tenecteplase
No intravenous tenecteplase only in subjects on direct oral anticoagulant (DOACs) or those planned for emergency endovascular thrombectomy (EVT)
• Conservative Blood Pressure Control
No or minimal Systolic Blood Pressure (SBP) control; SBP reduction by 5-10mmHg or a target of 175-180mmHg if very-high baseline SBP (=180mmHg); the timing of administration of interventions is specified to be immediately after randomisation; the intervention target is to be achieved ideally at 1 hour after randomisation and maintained for 24 hours (or until hospital discharge or death if this should occur earlier)
• Moderate Blood Pressure Control
SBP reduction by 10-20mmHg or a target of 160 ± 5, whichever is higher; no control if low-high baseline SBP (150-160mmHg); the timing of administration of interventions is specified to be immediately after randomisation; the intervention target is to be achieved ideally at 1 hour after randomisation and maintained for 24 hours (or until hospital discharge or death if this should occur earlier)
• Intensive Blood Pressure Control
SBP reduction by 30-50mmHg or a target of 140±5 mmHg, whichever is higher after endovascular thrombectomy (EVT); the timing of administration of interventions is specified to be immediately after randomisation; the intervention target is to be achieved ideally at 1 hour after randomisation and maintained for 24 hours (or until hospital discharge or death if this should occur earlier)
• Placebo
100 mL of 0.9% normal saline, administered as a single IV infusion with a 20-minute dosing duration.

Drug:
• NoNO-42
NoNO-42 at weight-based dosing - 2.6 mg/Kg, administered as a single IV infusion with a 20-minute dosing duration

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
The George Institute	Berry Consultants, University of Calgary

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	Mortality status equals to death which will be collected at all visits during the trial period	Platform level time frame: 90 days in Ischaemic Stroke State; Domain specific time frame may differ (details will be included in domain-specific registration)
Primary	modified Rankin scale (mRS) scores	The mRS is a 7-outcome ordered categorical scale that assesses functional neurological status after stroke. It is not intended for use as a measure of historical functional status. It is well accepted as a standard outcome around the world in the stroke community, by patients and by regulatory authorities. The seven values and the clinical summary of the individual scores are summarized in the following: 0 = No symptoms; = No significant disability; able to carry out all usual activities; = Slight disability; can look after own affairs, but unable to carry out all previous activities; = Moderate disability; require some help; = Moderately severe disability; unable to attend to own bodily needs without assistance; = Severe disability; bedridden and requiring constant nursing care and attention; = Dead	Platform level time frame: 90 days in Ischaemic Stroke State; Domain specific time frame may differ (details will be included in domain-specific registration)
Secondary	Excellent functional neurological outcome	Excellent functional neurological outcome means modified Rankin scale (mRS) scores 0-1. The minimum mRS is 0 (no symptoms) while the maximum mRS is 6 (death). The higher the mRS score is the worse outcome is.	Platform level time frame: 90 days in Ischaemic Stroke State; Domain specific time frame may differ (details will be included in domain-specific registration)
Secondary	Independent functional neurological outcome	Independent functional neurological outcome means modified Rankin scale (mRS) scores 0-2. The minimum mRS is 0 (no symptoms) while the maximum mRS is 6 (death). The higher the mRS score is the worse outcome is.	Platform level time frame: 90 days in Ischaemic Stroke State; Domain specific time frame may differ (details will be included in domain-specific registration)
Secondary	Health Related Quality of Life	Health Related Quality of Life based on EuroQol 5 Dimension 5 Level (EQ-5D-5L).The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems.	Platform level time frame: 90 days in Ischaemic Stroke State; Domain specific time frame may differ (details will be included in domain-specific registration)

External Links

•   ACT-GLOBAL ACT-42 Domain Registration Link
•   ACT-GLOBAL Blood Pressure Domain Registration Link
•   ACT-GLOBAL IV Thrombolysis Domain Registration Link