4000 Participants Needed

Tenecteplase for Stroke

(ACT-WHEN Trial)

Recruiting at 4 trial locations
BK
CA
Brian H. Buck, MD, FRCPC profile photo
Overseen ByBrian H. Buck, MD, FRCPC
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: University of Calgary
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have taken direct oral anticoagulants (DOACs) in the last 24 hours, it may affect how the treatment is administered.

What data supports the effectiveness of the drug Tenecteplase for stroke?

Research shows that Tenecteplase can lead to better early improvement in brain function after a stroke compared to another drug called alteplase. It also has practical advantages, like being easier to use, which has led some hospitals to prefer it for treating strokes.12345

Is tenecteplase generally safe for humans?

Research shows that tenecteplase is generally as safe as alteplase, a similar medication, for treating acute ischemic stroke. Studies found no significant differences in safety outcomes like bleeding in the brain or death between the two drugs.678910

How does the drug Tenecteplase differ from other stroke treatments?

Tenecteplase is unique because it is a genetically engineered version of a natural enzyme that helps dissolve blood clots, and it is administered as a single, quick injection, unlike some other treatments that require longer infusions.1112131415

What is the purpose of 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 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.

Research Team

BK

Bijoy K Menon, MD

Principal Investigator

University of Calgary

CA

Craig Anderson, MD

Principal Investigator

The George Institute

Eligibility Criteria

This trial is for up to 4,000 patients with acute ischemic stroke who are considered for intravenous thrombolysis. It's not clear what the specific inclusion or exclusion criteria are, but typically participants would need a confirmed diagnosis and be within a certain time frame from symptom onset.

Inclusion Criteria

I had a stroke and got to the hospital within 4.5 hours.
I have taken a DOAC medication or am planned for an emergency EVT.
I may qualify for IVT despite having conditions usually advised against it, as per my doctor's judgment.
See 1 more

Exclusion Criteria

I had a minor stroke but can still do most of my daily activities.
I don't have conditions that prevent me from receiving clot-dissolving drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous tenecteplase at either standard-dose (0.25 mg/kg) or low-dose (0.18 mg/kg) as a single bolus

Immediate administration post-randomization
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at Day 90

90 days
Day 90 assessment (in-person or by telephone)

Extension/Long-term follow-up

Participants may be monitored for additional outcomes and safety measures beyond the initial follow-up period

Long-term

Treatment Details

Interventions

  • Tenecteplase
Trial Overview The study compares different doses of tenecteplase (a clot-busting drug) in stroke treatment: standard-dose vs. low-dose, and its use with or without emergency endovascular thrombectomy (EVT). The goal is to find out which approach is more effective for patients including those recently on oral anticoagulants.
Participant Groups
3Treatment groups
Active Control
Group I: Standard-dose intravenous tenecteplase (0.25 mg/kg body weight)Active Control1 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.
Group II: 2) IVT with tenecteplase at low-dose: 0.18 mg/kgActive Control1 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 0.18 mg/kg body weight (maximum dose 18 mg) over 10-20 seconds as soon as possible after randomization.
Group III: 3) No IV thrombolysis [(only in those undergoing EVT or those on DOACs)Active Control1 Intervention
No intravenous tenecteplase only applied to subjects on DOACs over the last 24 hours or those planned for emergency EVT

Tenecteplase is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as TNKase for:
  • Acute ST elevation myocardial infarction (STEMI)
🇪🇺
Approved in European Union as Metalyse for:
  • Acute myocardial infarction

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials
827
Recruited
902,000+

The George Institute for Global Health, Australia

Collaborator

Trials
20
Recruited
50,200+

Findings from Research

In a meta-analysis of four randomized controlled trials with 1334 patients, tenecteplase showed a significant improvement in early major neurological outcomes compared to alteplase for treating acute ischemic stroke.
However, there were no significant differences in long-term functional outcomes, rates of intracerebral hemorrhage, or mortality between the two treatments, suggesting that while tenecteplase may offer early benefits, its overall safety and efficacy are comparable to alteplase.
Tenecteplase versus alteplase in acute ischemic stroke: systematic review and meta-analysis.Thelengana, A., Radhakrishnan, DM., Prasad, M., et al.[2020]
Tenecteplase (TNK) shows a higher rate of recanalization compared to alteplase in treating ischemic stroke, without increasing the risk of intracerebral hemorrhage, based on recent clinical trials.
While TNK demonstrates advantages in recanalization, its superiority over alteplase in improving functional outcomes and early neurological improvement is not consistently observed, indicating the need for further targeted clinical trials.
Tenecteplase in Ischemic Stroke: Challenge and Opportunity.Li, G., Wang, C., Wang, S., et al.[2022]
Intra-arterial administration of tenecteplase (TNK) for acute ischemic stroke was found to be safe, with no significant increase in intracranial hemorrhage compared to other thrombolytics or mechanical thrombectomy.
Patients treated with TNK showed a borderline significant trend towards better functional outcomes at 30 days, suggesting it may be as effective as current treatments, although further studies are needed to confirm these findings.
Intra-arterial tenecteplase for treatment of acute ischemic stroke: feasibility and comparative outcomes.Georgiadis, AL., Memon, MZ., Shah, QA., et al.[2018]

References

Tenecteplase versus alteplase in acute ischemic stroke: systematic review and meta-analysis. [2020]
Tenecteplase in Ischemic Stroke: Challenge and Opportunity. [2022]
Intra-arterial tenecteplase for treatment of acute ischemic stroke: feasibility and comparative outcomes. [2018]
Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke. [2021]
Tenecteplase versus alteplase before mechanical thrombectomy: experience from a US healthcare system undergoing a system-wide transition of primary thrombolytic. [2023]
Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS). [2023]
Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. [2018]
Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis. [2022]
Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Off-Label Use of Tenecteplase for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Incorporation of a new radioactive compound, 4+Sn-117m DTPA, into normal and burred rat femurs. [2016]
Fixation of distal femoral osteotomies with self-reinforced polymer/bioactive glass rods: an experimental study on rabbits. [2019]
13.United Statespubmed.ncbi.nlm.nih.gov
Biocompatibility of fixation materials in the brain. [2019]
[Evaluation of the usefulness of polytetrafluoroethylene (PTFE) prosthesis in cranioplasty. Experimental studies]. [2006]
Tetracalcium phosphate: Synthesis, properties and biomedical applications. [2010]
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