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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06320431




Registration number
NCT06320431
Ethics application status
Date submitted
5/02/2024
Date registered
20/03/2024
Date last updated
1/10/2024

Titles & IDs
Public title
ACT-GLOBAL THROMBOLYSIS (ACT-WHEN-001) Domain Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632
Scientific title
A Multicentre, Prospective, Randomized, Open Label, Blinded-endpoint Trial to Optimize the Use of Intravenous Tenecteplase in Participants with Acute Ischemic Stroke (ACT-GLOBAL THROMBOLYSIS (ACT WHEN-001) Within a Multi-faCtorial, MulTi-arm, Multi-staGe, Randomised, GLOBal Adaptive PLatform Trial for Stroke (ACT-GLOBAL) NCT06352632
Secondary ID [1] 0 0
ACT-WHEN-001
Universal Trial Number (UTN)
Trial acronym
ACT-WHEN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Ischemic Stroke AIS 0 0
Stroke Acute 0 0
Stroke, Acute, Stroke Ischemic 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tenecteplase

No intervention: Standard-dose intravenous tenecteplase (0.25 mg/kg body weight) - 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.

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

Active comparator: 3) No IV thrombolysis [(only in those undergoing EVT or those on DOACs) - No intravenous tenecteplase only applied to subjects on DOACs over the last 24 hours or those planned for emergency EVT


Treatment: Drugs: Tenecteplase
Thrombolytic
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
A reduction of functional dependence analyzed across the whole distribution of outcomes assessed on the modified Rankin Scale (mRS),
Timepoint [1] 0 0
From enrollment to the Day 90 assessment - Day 90 outcomes are assessed in a blinded manner
Secondary outcome [1] 0 0
90-day mortality
Timepoint [1] 0 0
From enrollment to the Day 90 assessment.
Secondary outcome [2] 0 0
Proportion of participants with a Modified Rankin Scale (mRS) of 0-1 at Day 90.
Timepoint [2] 0 0
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Secondary outcome [3] 0 0
Proportion of participants with a Modified Rankin Scale (mRS) of 0-2 at Day 90.
Timepoint [3] 0 0
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Secondary outcome [4] 0 0
Health-related quality of life, as measured by the EQ-5D-5L at Day 90.
Timepoint [4] 0 0
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Secondary outcome [5] 0 0
The frequencies of Serious Adverse Events (SAEs) from enrollment up to Day 4
Timepoint [5] 0 0
From enrollment ( randomization) to the Day 4
Secondary outcome [6] 0 0
Symptomatic intracranial hemorrhage
Timepoint [6] 0 0
Up to 36 hours from randomization
Secondary outcome [7] 0 0
Large parenchymal hemorrhage (PH-2)
Timepoint [7] 0 0
up to 36 hours from randomization
Secondary outcome [8] 0 0
Ordinal shift of 7 levels of mRS at 90 days
Timepoint [8] 0 0
Done by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)
Secondary outcome [9] 0 0
Proportion of participants achieving first pass (eTICI 2c or higher) reperfusion (when treated with EVT).
Timepoint [9] 0 0
Assessed and evaluated after the EVT procedure by the Central Imaging Core lab by blinded radiologists/stroke neurologists-the imaging reading will be done over the course of the trial through study completion.
Secondary outcome [10] 0 0
Proportion of participants achieving successful recanalization (revised arterial occlusive lesion [rAOL] score of 2b-3) at first angiographic acquisition (when treated with EVT).
Timepoint [10] 0 0
Assessed and evaluated after the EVT procedure by the Central Imaging Core lab by blinded radiologists/stroke neurologists. These imaging readings will be done over the course of the trial through study completion.
Secondary outcome [11] 0 0
Ambulatory status at discharge
Timepoint [11] 0 0
Completed the day the patient is discharged from hospital.
Secondary outcome [12] 0 0
Place of residence at 90 days
Timepoint [12] 0 0
Completed at the Day 90 follow-up visit
Secondary outcome [13] 0 0
Imaging assessment (e.g., infarct size and edema volume)
Timepoint [13] 0 0
Assessed and evaluated by the Central Imaging Core lab by blinded radiologists/stroke neurologists. These imaging readings will be performed over the course of the trial through study completion.
Secondary outcome [14] 0 0
Summative total length of hospital stay in the first 90-days after stroke onset
Timepoint [14] 0 0
Completed at the Day 90 follow-up visit.

Eligibility
Key inclusion criteria
1. 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.
2. Consent process completed as per national laws and regulation and the applicable ethics committee requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. Minor stroke patients with non-disabling symptoms.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/09/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2030
Actual
Sample size
Target
4000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Barangaro
Recruitment hospital [1] 0 0
The George Institute for Global Health - Sydney
Recruitment postcode(s) [1] 0 0
NSW 2000 - Sydney
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
A
Country [3] 0 0
Canada
State/province [3] 0 0
British Columbia
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
University of Calgary
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The George Institute for Global Health, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 24 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. In patients with recent (24 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. 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. 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. 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.
Trial website
https://clinicaltrials.gov/study/NCT06320431
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bijoy K Menon, MD
Address 0 0
University of Calgary
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bijoy K Menon, MD
Address 0 0
Country 0 0
Phone 0 0
4039448107
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06320431