ACT-GLOBAL Adaptive Platform Trial for Stroke

Condition(s) studied

Investigational drug(s) / intervention(s)

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

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.

NoNO-42: 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: No deferoxamine mesylate and no colchicine

Deferoxamine mesylate only: Deferoxamine mesylate at a dose of 32mg/kg/day via intravenous infusion immediately (within 1 hour) and continued for 2 consecutive days

Colchicine only: 0.5mg of oral colchicine daily for 30 days

Both deferoxamine mesylate and colchicine: 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: 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: Participants randomised to the No IA thrombolysis group will not receive IA thrombolysis.

Study 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.

Eligibility

Primary outcome measure(s)

• modified Rankin scale (mRS) scores — 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)
  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

Trial sites (2)

More The George Institute trials in Australia

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