NCT06352632

Brief 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20,000

participants targeted

Target at P75+ for phase_3 stroke

Timeline
101mo left

Started Sep 2024

Longer than P75 for phase_3 stroke

Geographic Reach
2 countries

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress16%
Sep 2024Sep 2034

First Submitted

Initial submission to the registry

April 2, 2024

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 8, 2024

Completed
6 months until next milestone

Study Start

First participant enrolled

September 26, 2024

Completed
9.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2034

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2034

Last Updated

November 21, 2024

Status Verified

November 1, 2024

Enrollment Period

9.9 years

First QC Date

April 2, 2024

Last Update Submit

November 18, 2024

Conditions

Keywords

Adaptive Platform TrialBlood PressureTenecteplaseIschaemic strokeIntracerebral Haemorrhage

Outcome Measures

Primary Outcomes (1)

  • 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

    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 (3)

  • Excellent functional neurological outcome

    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)

  • Independent functional neurological outcome

    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)

  • Health Related Quality of Life

    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)

Other Outcomes (1)

  • Mortality

    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)

Study Arms (4)

IV thrombolysis domain

EXPERIMENTAL

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.

Drug: Standard-dose intravenous tenecteplaseDrug: Low-dose intravenous tenecteplaseOther: No intravenous tenecteplase

Blood Pressure domain

EXPERIMENTAL

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.

Other: Conservative Blood Pressure ControlOther: Moderate Blood Pressure ControlOther: Intensive Blood Pressure Control

ACT-42 domain

EXPERIMENTAL

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.

Other: PlaceboDrug: NoNO-42

INTERACT5 Domain

EXPERIMENTAL

This is a domain within the Intracerebral Haemorrhage State of the ACT-GLOBAL adaptive platform trial for stroke. The objective of this domain is to determine the efficacy of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, compared to standard of care alone, on improving functional outcome in patients with acute spontaneous supratentorial ICH.

Other: No deferoxamine mesylate and no colchicineDrug: Deferoxamine mesylate onlyDrug: Colchicine onlyDrug: Both deferoxamine mesylate and colchicine

Interventions

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

IV thrombolysis domain

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

IV thrombolysis domain

No intravenous tenecteplase only in subjects on direct oral anticoagulant (DOACs) or those planned for emergency endovascular thrombectomy (EVT)

IV thrombolysis domain

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)

Blood Pressure domain

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)

Blood Pressure domain

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)

Blood Pressure domain
PlaceboOTHER

100 mL of 0.9% normal saline, administered as a single IV infusion with a 20-minute dosing duration.

ACT-42 domain

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

ACT-42 domain

No deferoxamine mesylate and no colchicine

INTERACT5 Domain

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

INTERACT5 Domain

0.5mg of oral colchicine daily for 30 days

INTERACT5 Domain

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

INTERACT5 Domain

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years
  • Clinical diagnosis of stroke

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

The George Institute for Global Health

Sydney, New South Wales, 2005, Australia

RECRUITING

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

Related Links

MeSH Terms

Conditions

StrokeIschemic StrokeCerebral Hemorrhage

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesIntracranial HemorrhagesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AlkaloidsHeterocyclic Compounds

Study Officials

  • Craig Anderson, MD, PhD

    The George Institute

    PRINCIPAL INVESTIGATOR
  • Bijoy Menon, MD

    University of Calgary

    PRINCIPAL INVESTIGATOR
  • Michael D Hill, MD

    University of Calgary

    PRINCIPAL INVESTIGATOR
  • Andrew Demchuk, MD

    University of Calgary

    PRINCIPAL INVESTIGATOR
  • Xiaoying Chen, PhD

    The George Institute

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Bijoy Menon, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Model Details: Adaptive Platform Trial evaluating multiple interventions in multiple states and domains
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 2, 2024

First Posted

April 8, 2024

Study Start

September 26, 2024

Primary Completion (Estimated)

September 1, 2034

Study Completion (Estimated)

September 1, 2034

Last Updated

November 21, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will share

After a domain is completed, the archived de-identified limited dataset of randomized participants will be transmitted to and stored in the ACT-GLOBAL Data Repository, for use by researchers. Data can be shared after publication of the main results unless specified otherwise in domain-specific registration.

Shared Documents
STUDY PROTOCOL
Time Frame
Data can be shared after publication of the main results.
Access Criteria
Data can be shared after publication of the main results, based on approval of a submitted protocol to the Publication Committee and relevant ethics review. Data can be shared to bona fide researchers with experience in medical research, and with no conflict of interest that may potentially influence their interpretation of any analyses, and employed by a recognised academic institute, health service organisation, commercial research organisation of from the pharmaceutical industry. The data sharing will be only for analyses within the constraints of the consent under which the data were originally gathered consent. Data sharing with industry will be according to relevant contracts with appropriate approvals from all stake holders.

Locations