Tenecteplase for Stroke

(ACT-WHEN Trial)

Recruiting at 23 trial locations

Overseen By Brian H. Buck, MD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Calgary

Must not be taking: DOACs

Disqualifiers: Active bleeding, Recent surgery, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 91

Duration: Immediate administration post-randomization

4000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best way to use tenecteplase, a clot-busting drug, for treating strokes caused by blocked blood vessels. Researchers compare different doses of the drug and assess its use with other treatments like endovascular thrombectomy, a procedure to remove clots. They seek to identify the most effective approach for people with recent strokes, particularly those who have taken blood thinners or require emergency procedures. Individuals who have experienced a significant stroke within the last 4.5 hours and might benefit from intravenous clot treatment may qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in stroke treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tenecteplase is generally safe for treating sudden strokes caused by blocked blood flow to the brain. Studies have found that it can help people recover abilities like speech and movement more quickly.

There is a risk of bleeding in the brain, known as symptomatic intracranial hemorrhage, but this is a known risk with stroke treatments. Doctors closely monitor for this after administering the drug.

Compared to another stroke treatment, alteplase, tenecteplase is similarly safe, with no major differences in side effects. People who have used tenecteplase in the past have generally shown good recovery of abilities after a stroke.

In summary, research considers tenecteplase safe. It offers a balance of benefits and risks that doctors evaluate when selecting it as a treatment option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for ischemic stroke, like alteplase, work by dissolving blood clots to restore blood flow to the brain. But tenecteplase, the study drug, has some exciting advantages. It’s administered as a single, quick bolus, making it easier and faster to use than the continuous infusion required for alteplase. Additionally, tenecteplase has a longer half-life, which could potentially improve outcomes by sustaining its clot-busting effects. Researchers are particularly interested in exploring both standard and lower doses to find the safest and most effective option for patients, especially for those who are unable to receive traditional IV thrombolysis.

What evidence suggests that this trial's treatments could be effective for acute ischemic stroke?

Research has shown that tenecteplase effectively treats sudden strokes caused by blocked blood flow to the brain. Studies have found that it helps people recover faster. Approximately 37% of patients treated with tenecteplase can return to their daily activities with little or no disability, which is similar to or slightly better than results for alteplase, another stroke treatment. Tenecteplase also effectively breaks down clots when used within 4.5 hours of stroke onset. Overall, it is considered a strong option for stroke treatment.

In this trial, participants will receive either a standard dose of tenecteplase (0.25 mg/kg) or a low dose (0.18 mg/kg) to evaluate its effectiveness and safety at different dosages. ^{1 2 3 4 6}

Who Is on the Research Team?

Bijoy K Menon, MD

Principal Investigator

University of Calgary

Craig Anderson, MD

Principal Investigator

The George Institute

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Standard-dose intravenous tenecteplase (0.25 mg/kg body weight) Active Control 1 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/kg Active Control 1 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 Control 1 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

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+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial tenecteplase for treatment of acute ischemic stroke: feasibility and comparative outcomes. Georgiadis, AL., Memon, MZ., Shah, QA., et al.[2018]

In a meta-analysis of six nonrandomized studies involving 1820 patients, tenecteplase showed higher odds of achieving a good functional outcome at 90 days compared to alteplase, suggesting it may be more effective for treating acute ischemic stroke.

Tenecteplase was found to be as safe as alteplase, with no significant differences in rates of symptomatic intracranial hemorrhage or parenchymal hematoma, supporting its use in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label Use of Tenecteplase for the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis. Katsanos, AH., Psychogios, K., Turc, G., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase in acute ischemic stroke: systematic review and meta-analysis. Thelengana, A., Radhakrishnan, DM., Prasad, M., et al.[2020]

In a study of 148 patients with acute ischemic stroke, those treated with tenecteplase (TNK) showed a significantly higher rate of spontaneous recanalization (23.5%) compared to those treated with alteplase (TPA) (10.3%), suggesting TNK may be more effective in restoring blood flow in large vessel occlusion cases.

The safety profile of TNK was comparable to TPA, with similar rates of symptomatic intracranial hemorrhage, 90-day mortality, and functional outcomes, indicating that TNK is a safe alternative for thrombolytic therapy in acute ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase before mechanical thrombectomy: experience from a US healthcare system undergoing a system-wide transition of primary thrombolytic. Hendrix, P., Collins, MK., Griessenauer, CJ., et al.[2023]

The new tin radiopharmaceutical, 4+Sn-117m DTPA, has a favorable half-life of 14 days for physical decay and 7.8 days for biological decay, making it suitable for therapeutic use in orthopedics.

This compound shows a strong affinity for newly calcified bone, which could enhance targeted treatment in orthopedic applications, while demonstrating a significant difference in retention between skeletal and whole body tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of a new radioactive compound, 4+Sn-117m DTPA, into normal and burred rat femurs. Hurst, LC., Badalamente, MA., Oster, ZH., et al.[2016]

In a study involving 48 juvenile New Zealand White rabbits, commercially pure titanium and vitallium microscrews showed similar inflammatory responses in the brain after 26 weeks, indicating they are relatively biocompatible, though still more inflammatory than silicone elastomer, a well-established neurosurgical material.

316L stainless steel wire caused the highest inflammatory response over time, suggesting it may not be the best choice for craniofacial fixation due to potential neurotoxicity compared to titanium and vitallium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biocompatibility of fixation materials in the brain. Mofid, MM., Thompson, RC., Pardo, CA., et al.[2019]

Tenecteplase is as safe and effective as alteplase for treating acute ischemic stroke, based on a meta-analysis of 14 studies involving 3537 patients, showing no significant differences in 90-day outcomes.

Patients treated with tenecteplase may experience higher rates of early neurological improvement compared to those treated with alteplase, suggesting a potential advantage in the initial recovery phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis. Ma, P., Zhang, Y., Chang, L., et al.[2022]

In a study of 71 patients with tandem lesion strokes, tenecteplase (TNK) showed a higher rate of intracranial reperfusion (20%) compared to alteplase (7%), suggesting TNK may be more effective in restoring blood flow in these cases.

However, there were no significant differences in functional outcomes, mortality, or rates of symptomatic intracranial hemorrhage between TNK and alteplase, indicating that both treatments have similar safety and efficacy profiles for patients with tandem lesion strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials. Yogendrakumar, V., Churilov, L., Mitchell, PJ., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase in Ischemic Stroke: Challenge and Opportunity. Li, G., Wang, C., Wang, S., et al.[2022]

In a study of 165 patients treated with tenecteplase for ischemic stroke, the safety profile was comparable to that of 254 patients treated with alteplase, with similar rates of symptomatic intracranial hemorrhage (1.8% vs. 2.7%) and angioedema (2.4% vs. 0.4%).

The use of tenecteplase was found to be feasible and effective, showing no significant difference in functional independence at 90 days compared to alteplase, indicating it can be a viable alternative for stroke treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke. Zhong, CS., Beharry, J., Salazar, D., et al.[2021]

In a study involving 36 rabbits, self-reinforced poly(DTE carbonate) and poly(DTE carbonate)/bioactive glass rods were found to be effective for fixing bone osteotomies, showing suitable mechanical strength for this purpose.

The poly(DTE carbonate)/bioactive glass rods maintained their mechanical properties better over time compared to the poly(DTE carbonate) rods, with less reduction in bending and shear strength after 100 weeks, indicating a potential advantage for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixation of distal femoral osteotomies with self-reinforced polymer/bioactive glass rods: an experimental study on rabbits. Pyhältö, T., Lapinsuo, M., Pätiälä, H., et al.[2019]

In a study involving 12 cats, cranial bone defects were successfully reconstructed using tarflen (PTFE) plates, indicating potential for use in cranioplastic surgery.

Histopathological analysis over a 3-month observation period revealed that tarflen is chemically inactive, suggesting it may be a safe option for long-term implantation in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the usefulness of polytetrafluoroethylene (PTFE) prosthesis in cranioplasty. Experimental studies]. Zaborski, G., Szot, W.[2006]

Monoclinic tetracalcium phosphate (TTCP) is a unique calcium phosphate with a higher calcium-to-phosphate ratio than hydroxyapatite, making it valuable in biomaterials for bone applications.

TTCP is commonly used in self-setting calcium phosphate bone cements that convert to hydroxyapatite in the body, demonstrating its effectiveness in promoting bone healing and integration with implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetracalcium phosphate: Synthesis, properties and biomedical applications. Moseke, C., Gbureck, U.[2010]

A comprehensive analysis of 19,514,140 case reports revealed that while tenecteplase is as effective as alteplase for treating acute ischemic stroke, it has a higher incidence of serious adverse events (AEs) such as death and cardiogenic shock, indicating potential safety concerns.

Unexpected adverse reactions, including ocular issues and pneumonia aspiration, were identified with tenecteplase, highlighting the need for ongoing monitoring to ensure patient safety before it can be considered a full alternative to alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS). Shi, FE., Yu, Z., Sun, C., et al.[2023]

In a study involving 1585 patients across 5 randomized clinical trials, tenecteplase showed significantly greater complete recanalization and early neurological improvement compared to alteplase in treating acute ischemic stroke.

Both treatments had similar safety profiles, with no significant differences in rates of recovery, functional independence, or serious complications like intracerebral hemorrhage, indicating that tenecteplase is at least as effective and safe as alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. Kheiri, B., Osman, M., Abdalla, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12402402/

Efficacy and Safety of Tenecteplase in Acute Ischemic Stroke Tenecteplase improves early neurological recovery and recanalization and provides excellent functional outcomes in acute ischemic stroke.

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.125.053256

Tenecteplase for Acute Ischemic Stroke at 4.5 to 24 Hours The efficacy outcomes comprised: (1) excellent functional outcome (mRS score, 0–1 at 90 days), (2) good functional outcome (mRS score, 0–2 at 90 ...

3. tnkase.com tnkase.com/acute-ischemic-stroke/clinical-data/act-trial-efficacy.html

TNKase® (tenecteplase) | Efficacy in Acute Ischemic Stroke 37% of TNKase-treated patients had excellent functional outcomes (defined as mRS 0-1) 90 to 120 days following a stroke vs ~36% for alteplase.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831320

Safety and Effectiveness for Tenecteplase and Alteplase in ... This comparative effectiveness study compares the clinical effectiveness and safety of tenecteplase and alteplase for the treatment of acute ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2402980

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without ... Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1052305725001168

An updated meta-analysis of randomized controlled trials Data regarding the efficacy and safety of tenecteplase (TNK) in patients with acute ischemic stroke (AIS) who present outside the standard treatment window ...