ACT-GLOBAL Adaptive Platform Trial for Stroke

ConditionStroke

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age18+

SponsorThe George Institute

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years

Clinical diagnosis of stroke

Disqualifiers

None

Trial design

Design model

Factorial

Treatments tested in this trial

Standard-dose intravenous tenecteplase
Drug
Standard-dose intravenous tenecteplase (0.25 mg/kg body weight); one-time IV bolus injection soon after randomisation
Low-dose intravenous tenecteplase
Drug
Low-dose intravenous tenecteplase (0.18 mg/kg body weight); one-time IV bolus injection soon after randomisation
No intravenous tenecteplase
Other intervention
No intravenous tenecteplase only in subjects on direct oral anticoagulant (DOACs) or those planned for emergency endovascular thrombectomy (EVT)
Conservative Blood Pressure Control
Other intervention
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
Other intervention
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
Other intervention
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
Other intervention
100 mL of 0.9% normal saline, administered as a single IV infusion with a 20-minute dosing duration.
NoNO-42
Drug
NoNO-42 at weight-based dosing - 2.6 mg/Kg, administered as a single IV infusion with a 20-minute dosing duration
No deferoxamine mesylate and no colchicine
Other intervention
No deferoxamine mesylate and no colchicine
Deferoxamine mesylate only
Drug
Deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) and continued for 2 consecutive days
Colchicine only
Drug
0.5mg of oral colchicine daily for 30 days
Both deferoxamine mesylate and colchicine
Drug
Deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) and continued for 2 consecutive days; plus 0.5mg of oral colchicine daily for 30 consecutive days
IA thrombolysis
Drug
Participants randomised to the IA thrombolysis group will receive IA thrombolysis (tenecteplase or alteplase) at the time of completion of the mechanical thrombectomy part of the EVT procedure. Tenecteplase will be given at a dose of 0.0625mg/kg (maximum dose of 6.25mg) and alteplase at a dose of 0.225 mg/kg (maximum dose 22.5mg) intraarterially by the treating neuro-interventional staff. The selection of thrombolytic agent will be determined according to local availability. The study drug dose will be increased to 0.125 mg/ kg (maximum dose 12.5mg) for tenecteplase or 0.45 mg/kg (maximum dose 40mg) for alteplase if above dose meet prespecified posterior probabilities at the first or second interims per adaptive design report.
no IA thrombolysis
Other intervention
Participants randomised to the No IA thrombolysis group will not receive IA thrombolysis.

Treatment groups

20,000 Participants

are divided into 5 treatment groups

Group A: IV thrombolysis domainExperimental treatment 3 interventions

Group B: Blood Pressure domainExperimental treatment 3 interventions

Group C: ACT-42 domainExperimental treatment 2 interventions

Group D: INTERACT5 DomainExperimental treatment 4 interventions

Group E: IA Thrombolysis DomainExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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 1. = No significant disability; able to carry out all usual activities 2. = Slight disability; can look after own affairs, but unable to carry out all previous activities 3. = Moderate disability; require some help 4. = Moderately severe disability; unable to attend to own bodily needs without assistance 5. = Severe disability; bedridden and requiring constant nursing care and attention 6. = Dead

Time frame

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

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.

Time frame

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.

Time frame

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.

Time frame

Other outcomes

Mortality

Mortality status equals to death which will be collected at all visits during the trial period

Time frame

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)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

The George Institute

Lead sponsor

University of Calgary

Collaborator

Berry Consultants

Collaborator

Source ClinicalTrials.gov

Apply now