ACT-GLOBAL THROMBOLYSIS (ACT-WHEN-001) Domain Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Calgary
About this trial
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. 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. 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Tenecteplase
DrugThrombolytic
Treatment groups
4,000 Participants
are divided into 3 treatment groupsGroup A: Standard-dose intravenous tenecteplase (0.25 mg/kg body weight)No intervention 0 interventions
Group B: 2) IVT with tenecteplase at low-dose: 0.18 mg/kgActive comparator 1 intervention
Group C: 3) No IV thrombolysis [(only in those undergoing EVT or those on DOACs)Active comparator 1 intervention
Trial outcomes
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.
Time frame
From enrollment to the Day 90 assessment - Day 90 outcomes are assessed in a blinded mannerSecondary outcomes
1
90-day mortality
Date and cause of death are collected from randomization until End of Study.
Time frame
From enrollment to the Day 90 assessment.2
Proportion of participants with a Modified Rankin Scale (mRS) of 0-1 at Day 90.
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.
Time frame
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)3
Proportion of participants with a Modified Rankin Scale (mRS) of 0-2 at Day 90.
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.
Time frame
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)4
Health-related quality of life, as measured by the EQ-5D-5L at Day 90.
The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The version of the instrument selected for the trial is interviewer administered either in-person, or by telemedicine or by telephone. The respondents will also rate their overall health on the day of the interview on a 0-100 visual analogue scale (EQ-VAS).
Time frame
Completed by telephone at the Day 90 assessment (Day 90 outcomes are assessed in a blinded manner)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Calgary
Lead sponsor
The George Institute for Global Health, Australia
Collaborator
Source ClinicalTrials.gov