ACT-GLOBAL THROMBOLYSIS (ACT-WHEN-001) Domain Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632

NCT06320431 | Recruiting Phase 3 DMC

• 1 other identifier: ACT-WHEN-001
• Study Type: interventional
• Target: 4,000
• Locations: 2 countries
• Sites: 24

Brief Summary

This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design. Up to 4,000 patients with presumed acute ischemic stroke (AIS) 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. This domain aim is to efficiently, reliably, and simultaneously, determine the comparative effectiveness of intravenous thrombolysis (IVT) using standard-dose intravenous tenecteplase (0.25 mg/kg body weight), vs. low-dose intravenous tenecteplase (0.18 mg/kg body weight) in all patients who present to hospital with acute ischemic stroke and are considered for intravenous thrombolysis. In addition, this domain also seeks to study standard-dose intravenous tenecteplase (0.25 mg/kg body weight), vs. low-dose intravenous tenecteplase (0.18 mg/kg body weight) vs. no TNK upfront with rescue IA TNK if necessary (in those eligible for emergency EVT) and no TNK upfront in those who have taken DOACs during the preceding 48 hours. This domain therefore seeks to generate more robust randomized evidence to guide clinicians in their decisions over the balance of risks and treatment with intravenous thrombolysis with tenecteplase wherever such evidence is currently insufficient. This domain will currently evaluate four research questions in relation to the use of IVT with tenecteplase:

1. 1.In patients with recent (48 hours) intake of a standard-dose direct oral anticoagulant (DOAC), how should IVT be used? - Use standard-dose (0.25 mg/kg body weight) or low-dose tenecteplase (0.18 mg/kg) or not at all.
2. 2.In patients planned to be treated with endovascular thrombectomy, how should tenecteplase be used? -Treat with IV tenecteplase (standard- or low-dose) or not at all.
3. 3.In any patient receiving IVT, what is the optimal dose of tenecteplase? - use standard-dose (0.25 mg/kg body weight) or low-dose tenecteplase (0.18 mg/kg).
4. 4.To what extent is the treatment effect of standard- vs. low-dose tenecteplase modified by key patient characteristics, such as diabetes, prior antiplatelet therapy, renal failure, or frailty, old age or having a heavy burden of cerebral small vessel disease on brain imaging.

Conditions

Acute Ischemic Stroke AIS; Stroke Acute; Stroke, Acute, Stroke Ischemic

Keywords

Stroke; Thrombolysis; Platform; Tenecteplase; Endovascular thrombectomy; EVT; Domain

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 (14)

• 90-day mortality

  From enrollment to the Day 90 assessment.

• 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)

• 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)

• 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)

• The frequencies of Serious Adverse Events (SAEs) from enrollment up to Day 4

  From enrollment ( randomization) to the Day 4

Study Arms (3)

Standard-dose intravenous tenecteplase (0.25 mg/kg body weight)

NO INTERVENTION

The intervention group will receive intravenous tenecteplase as a single bolus as per the standard manufacturers' instructions for use. The dose administered will be 0.25 mg/kg body weight (maximum dose 25 mg) over 10-20 seconds as soon as possible after randomization.

2) IVT with tenecteplase at low-dose: 0.18 mg/kg

ACTIVE COMPARATOR

The intervention group will receive intravenous tenecteplase as a single bolus as per the standard manufacturers' instructions for use. The dose administered will be 0.18 mg/kg body weight (maximum dose 18 mg) over 10-20 seconds as soon as possible after randomization.

Drug: Tenecteplase

3) No IV thrombolysis [(only in those undergoing EVT or those on DOACs)

ACTIVE COMPARATOR

No intravenous tenecteplase only applied to subjects on DOACs over the last 24 hours or those planned for emergency EVT

Drug: Tenecteplase

Interventions

Tenecteplase DRUG

Thrombolytic

Also known as: TNKase, Metalyse

2) IVT with tenecteplase at low-dose: 0.18 mg/kg; 3) No IV thrombolysis [(only in those undergoing EVT or those on DOACs)

Eligibility Criteria

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

You may qualify if:

• All patients with disabling AIS presenting within 4.5 hours of symptom onset or last known well who may benefit from intravenous thrombolysis (IVT) with tenecteplase. Patients potentially eligible for IVT with conditions described as relative contraindications in national guidelines where physician discretion is recommended are eligible. Patients who received a DOAC, and those planned for emergency EVT are eligible.
• Consent process completed as per national laws and regulation and the applicable ethics committee requirements.

You may not qualify if:

• Any absolute contraindication for IV thrombolysis per current national guidelines. Examples include those who are actively bleeding, had recent intracranial surgery, head trauma, intracranial or subarachnoid hemorrhage, or a bleeding diathesis.
• Minor stroke patients with non-disabling symptoms.

Sponsors & Collaborators

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

Study Sites (24)

The George Institute for Global Health

Sydney, Barangaroo, NSW 2000, Australia

NOT YET RECRUITING

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

RECRUITING

Monash University (Box Hill)

Melbourne, Victoria, Australia

RECRUITING

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

Medicine Hat Regional Hospital

Medicine Hat, Alberta, Canada

NOT YET RECRUITING

Red Deer Regional Hospital

Red Deer, Alberta, Canada

NOT YET RECRUITING

University of Alberta

Edmonton, A, Canada

RECRUITING

Kelowna Regional Hospital

Kelowna, British Columbia, Canada

NOT YET RECRUITING

Royal Columbian Hospital

New Westminster, British Columbia, Canada

NOT YET RECRUITING

University of British Columbia

Vancouver, British Columbia, Canada

RECRUITING

Brandon Regional Hospital

Brandon, Manitoba, Canada

NOT YET RECRUITING

University of Manitoba - Winnipeg Health Science Centre

Winnipeg, Manitoba, Canada

RECRUITING

Queen Elizabeth II Health Science Center (Halifax)

Halifax, Nova Scotia, Canada

NOT YET RECRUITING

Health Sciences North Horizon Sante-Nord

Greater Sudbury, Ontario, Canada

RECRUITING

McMaster University Hamilton Health Sciences Centre

Hamilton, Ontario, Canada

RECRUITING

Kingston General Hospital

Kingston, Ontario, Canada

NOT YET RECRUITING

Lawson Health Research Institute- London

London, Ontario, Canada

NOT YET RECRUITING

University of Ottawa

Ottawa, Ontario, Canada

RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

RECRUITING

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

RECRUITING

Queen Elizabeth Hospital (PEI)

Charlottetown, Prince Edward Island, Canada

RECRUITING

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

NOT YET RECRUITING

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

Sherbrooke, Quebec, Canada

NOT YET RECRUITING

Royal University Hospital

Saskatoon, Saskatchewan, Canada

RECRUITING

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; 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

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

4039448107; bkmmenon@ucalgary.ca

Craig Anderson, MD

CONTACT

4039448107; 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: MD

Model Details: Randomization will be stratified by: (1) planned emergency endovascular thrombectomy (EVT) and (2) known use or history to suggest use of a standard-dose direct oral anticoagulant (DOAC) within the last 48 hours. Randomization will be centralized, secure and concealed, using a web-based server and permuted blocks of varying sizes will be used. This will result in four pre-defined strata: (i) EVT+ / DOAC+ (ii) EVT+ / DOAC- (iii) EVT- / DOAC+ and (iv) EVT- / DOAC-. Patients in strata 1, 2 and 3 will be randomized to standard-dose IV tenecteplase (0.25 mg/kg body weight) vs. Low-dose tenecteplase (0.18 mg/kg body weight) or no IV thrombolysis (1:1:1 randomization). Patients in strata 4 will be randomized to standard-dose intravenous (IV) tenecteplase (0.25 mg/kg body weight) vs. Low-dose IV tenecteplase (0.18 mg/kg body weight) only (1:1 randomization). Emergency EVT is defined as anticipated arterial puncture time in the enrolling hospital ≤ 60 minutes from randomization.

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: March 20, 2024
• Study Start: September 26, 2024
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 17, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); CA (21)