ACT-GLOBAL Adaptive Platform Trial for Stroke

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.

Conditions

• Stroke

Interventions

DRUG

Standard-dose intravenous tenecteplase

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

DRUG

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)

OTHER

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)

OTHER

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)

OTHER

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)

OTHER

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

OTHER

No deferoxamine mesylate and no colchicine

No deferoxamine mesylate and no colchicine

DRUG

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

DRUG

Colchicine only

0.5mg of oral colchicine daily for 30 days

DRUG

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

DRUG

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.

OTHER

no IA thrombolysis

Participants randomised to the No IA thrombolysis group will not receive IA thrombolysis.

Sponsors & Collaborators

• University of Calgary

  collaborator OTHER

• Berry Consultants

  collaborator OTHER

• The George Institute

  lead OTHER

Principal Investigators

• Craig Anderson, MD, PhD · The George Institute

• Bijoy Menon, MD · University of Calgary

• Michael D Hill, MD · University of Calgary

• Andrew Demchuk, MD · University of Calgary

• Xiaoying Chen, PhD · The George Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-09-26

Primary Completion

2034-09-30

Completion

2034-09-30

Countries

• Australia
• Canada

Study Locations