ACT-GLOBAL IA Thrombolysis(ACT-REACT-004)Domain Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632

NCT07687056 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: ACT REACT-004ACT GLOBAL
• Study Type: interventional
• Target: 1,500
• Locations: 2 countries
• Sites: 13

Brief Summary

Study Design and Duration: This domain will be conducted as part of ACT-GLOBAL platform trial and will have the nested domain name of REACT. It has a prospective, randomised, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design of up to 1,500 subjects with Acute Ischemic Stroke (AIS) who undergo EVT. Randomisation will be stratified by country/ region, and the IA thrombolytic agent (tenecteplase or alteplase). Minimal sufficient balance algorithm will operate within each stratum to preserve balance on key covariates while maintaining allocation randomness. Participants will be followed for 90 days (or until death, if prior to 90 days). The end of the trial is defined as the date that all participants have completed their Day 90 assessment. Primary outcome data will be determined by simplified, structured method of assessment using the modified Rankin scale (mRS), conducted through centralized telephone interviews or online media performed by central trial personnel blinded to treatment assignment and received. Domain Interventions: The intervention group will receive a single dose of local intraarterial thrombolysis using either tenecteplase (at a dose of 0.0625mg/kg; maximum dose of 6.25mg) or alteplase (0.225 mg/kg; maximum dose, 20mg) at the end of EVT procedure plus standard of care while the control group will receive standard of care alone. The selection of the thrombolytic agent will be determined according to local availability. The dose of intraarterial thrombolysis will be increased if the above dose meets prespecified posterior probabilities at the first or second interims. In all eligible patients:

1. 1.Local intra-arterial thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg\*
2. 2.No intra-arterial thrombolysis.
3. 3.The dose of IA thrombolysis may be doubled to 0.125 mg/kg tenecteplase or 0.45 mg/kg alteplase if this dose shows futility at pre-specified interims Randomization will be stratified by country/ region, the IA thrombolytic agent used (tenecteplase or alteplase). IA thrombolysis will be administered as a one-time treatment.

Conditions

Stroke, Acute Ischemic; Endovascular Thrombectomy; Acute Ischemic Stroke AIS

Keywords

Tenecteplase; Alteplase; Intra-arterial thrombolysis; Stroke; Endovascular Thrombectomy; EVT; Domain; Platform; Thrombolysis

Outcome Measures

Primary Outcomes (1)

• A reduction of functional dependence analyzed across the whole distribution of outcomes assessed on the modified Rankin Scale (mRS),

  Modified Rankin Scale (mRS) -which scores of 0 to 1 indicate a favourable outcome without or with symptoms but no disability, scores of 2 to 5 indicate increasing levels of disability (and dependency), and a score of 6 indicates death.

  From enrollment to the Day 90 assessment - Day 90 outcomes are assessed in a blinded manner

Secondary Outcomes (1)

• Rate of 90-day mortality

  From enrollment to the Day 90 assessment.

Other Outcomes (13)

• The Proportion of participants with a Modified Rankin Scale (mRS) of 0-1 at Day 90.

  Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)

• The Proportion of participants with a Modified Rankin Scale (mRS) of 0-2 at Day 90.

  Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)

• Rating the Health-related quality of life, as measured by the EQ-5D-5L at Day 90.

  Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)

Study Arms (2)

Local intra-arterial (IA) thrombolysis using either tenecteplase or alteplase

ACTIVE COMPARATOR

The intervention group will receive local intra-arterial (IA) thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg.

Biological: Tenecteplase or Alteplase- depending upon availability at each treating centre

No IA thrombolysis

PLACEBO COMPARATOR

No intra-arterial thrombolysis.

Other: Control

Interventions

Tenecteplase or Alteplase- depending upon availability at each treating centre BIOLOGICAL

Intra-arterial thrombolysis after endovascular therapy

Also known as: Thrombolytic (2 options), tNKase, Metalyse,, tPA, Activase

Local intra-arterial (IA) thrombolysis using either tenecteplase or alteplase

Control OTHER

No intra-arterial thrombolysis after endovascular therapy

No IA thrombolysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Clinical diagnosis of stroke

Sponsors & Collaborators

• University of Calgary: lead
• The George Institute for Global Health, Australia: collaborator

Study Sites (13)

The George Institute for Global Health

Sydney, Barangaroo, NSW 2000, Australia

Location

University of Calgary- Foothills Medical Centre

Calgary, Alberta, T2N2T9, Canada

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Kelowna Regional Hospital

Kelowna, British Columbia, Canada

Location

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Location

University of British Columbia

Vancouver, British Columbia, Canada

Location

University of Manitoba - Winnipeg Health Science Centre

Winnipeg, Manitoba, Canada

Location

Health Sciences North Horizon Sante-Nord

Greater Sudbury, Ontario, Canada

Location

Ottawa Civic Hospital

Ottawa, Ontario, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Location

CHUM -Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Location

CIUSSS de l'Estrie - CHUS Fleurimont Hôpital (Sherbrooke)

Sherbrooke, Quebec, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Location

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Tenecteplase; Fibrinolytic Agents; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cardiovascular Agents; Therapeutic Uses; Hematologic Agents; Biological Factors

Study Officials

• Bijoy K Menon, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Craig Anderson, MD

  The George Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bijoy K Menon, MD

CONTACT

403-944-8107; bkmmenon@ucalgary.ca

Craig Anderson, MD

CONTACT

403-944-8107; canderson@georgeinstitute.org.au

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The trial will have allocation concealment and blinded endpoint assessment, but open-label treatment. Given the time sensitive nature of acute stroke treatment, blinding the enrolling personnel to treatment assignment is not practical. Clinical site staff, including the Principal Investigator (PI), sub-investigators, clinic site staff, and the Sponsor will not be blinded to treatment allocated or received. In the event of an emergency the PI will be already unblinded. The trial will have blinded endpoint assessment on Day 90, with central blinded assessors contacting the participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ACT GLOBAL Principal Investigator, Clinical Professor of Neurology, Section Head, MD

Model Details: Patients will be randomized to IA thrombolysis (using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg) vs no IA thrombolysis (1:1 randomization). Randomization will be stratified by country/ region, the IA thrombolytic agent used (tenecteplase or alteplase). Randomization will be centralized, secure and concealed, using a web-based server and minimal sufficient balance method (minimization procedure) will be used to achieve distribution balance for key variables.

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: July 7, 2026
• Study Start: June 10, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): March 31, 2031
• Last Updated: July 7, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12); AU (1)