Intra-Arterial Tenecteplase for Stroke

(TNK-FLOW Trial)

Overseen By Anna Maria Swiatek, MSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Oral anticoagulants, Thrombolytics

Disqualifiers: Bleeding, Hypertension, Stroke history, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Immediate

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the safety and feasibility of using intra-arterial Tenecteplase in patients undergoing blood clot extraction for treatment of acute ischemic (non-bleeding) stroke. Tenecteplase is a drug that is currently FDA-approved to treat a heart attack but not currently approved for stroke treatment.

Will I have to stop taking my current medications?

The trial requires that you have not used certain oral anticoagulants (blood thinners) like dabigatran, rivaroxaban, apixaban, or edoxaban within the last 48 hours. If you are on these medications, you may need to stop them before participating.

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

Research shows that Tenecteplase is as effective as another drug, Alteplase, for treating strokes, and it may even work better in some cases by helping to open blocked blood vessels in the brain. It has been used successfully in different hospitals, showing it can be a reliable option for stroke treatment. ^{1 2 3 4 5}

Is tenecteplase safe for use in humans?

Research shows that tenecteplase is generally as safe as alteplase, a similar drug, for treating acute ischemic stroke. Studies found no significant differences in safety outcomes like bleeding in the brain or death between the two drugs. ^{6 7 8 9 10}

How is the drug tenecteplase unique in treating stroke?

Tenecteplase is a genetically engineered drug that can be administered directly into the artery (intra-arterial) for treating acute ischemic stroke, which may offer faster and more effective treatment for large vessel blockages compared to the standard drug alteplase. It is also being studied for its potential to avoid the need for mechanical procedures to remove clots. ^{2 11 12 13 14}

Research Team

Rahul Karamchandani, MD

Principal Investigator

Atrium Health Neurosciences Institute

Eligibility Criteria

This trial is for adults who were independent before their stroke, have a moderate to severe blockage in the brain's large arteries, and can get treatment within 4.5 to 24 hours of symptoms starting. They must not have serious bleeding risks or other major health issues that could interfere with the study.

Inclusion Criteria

I was independent in daily activities before my current health issue.

Baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 6

I had stroke symptoms due to a blocked artery in my neck or brain within the last 24 hours.

Exclusion Criteria

I have a brain tumor or blood vessel problem larger than 1 cm.

I have had a recent brain bleed seen on imaging before or after a clot removal procedure.

My blood pressure remains high after treatment, despite medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a one-time dose of intra-arterial Tenecteplase or saline following endovascular thrombectomy

Immediate

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and effectiveness, including assessment of symptomatic intracranial hemorrhage and neurological improvement

36 hours

1 visit (in-person)

Extended Follow-up

Participants are monitored for long-term outcomes, including mortality and functional status using the Modified Rankin Scale and other measures

90 days

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Tenecteplase

Trial Overview The trial tests if Tenecteplase, a drug approved for heart attacks but not strokes, is safe when given directly into an artery after mechanical clot removal in stroke patients. It compares this method to using saline (saltwater solution).

Participant Groups

Group I: Intra-arterial Tenecteplase Experimental Treatment 1 Intervention

Following endovascular thrombectomy for large vessel occlusion stroke one-time dose of intra-arterial Tenecteplase (0.125 mg/kg, maximum dose 12.5 mg) will be delivered over 5-10 seconds by the treating neuro-interventionalist through a microcatheter positioned as close as possible to the residual thrombus or as distal as possible in the originating vessel, per the discretion of the neuro-interventionalist.

Group II: Intra-arterial Saline Placebo Group 1 Intervention

Following endovascular thrombectomy for large vessel occlusion stroke one-time dose of saline (0.9% NaCl solution) will be delivered over 5-10 seconds by the treating neuro-interventionalist through a microcatheter positioned as close as possible to the residual thrombus or as distal as possible in the originating vessel, per the discretion of the neuro-interventionalist.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

In acute ischemic stroke, early IV tenecteplase was noninferior to alteplase for excellent functional outcome. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Tenecteplase Averting Mechanical Thrombectomy in Emergent Large Vessel Occlusion. [2020]

3. India pubmed.ncbi.nlm.nih.gov

Acute ischemic stroke thrombolysis with tenecteplase: An institutional experience from South India. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke. [2021]

5. Uganda pubmed.ncbi.nlm.nih.gov

Thrombolysis for acute ischemic stroke by tenecteplase in the emergency department of a Moroccan hospital. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS). [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. [2018]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Tenecteplase vs. Alteplase for Intravenous Thrombolytic Therapy of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations. [2022]

11. Scotland pubmed.ncbi.nlm.nih.gov

Complete recovery following intra-arterial tenecteplase administration in a woman with acute ischemic stroke. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Major Bleeding Postadministration of Tenecteplase Versus Alteplase in Acute Ischemic Stroke. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Evolving Thrombolytics: from Alteplase to Tenecteplase. [2023]

14. France pubmed.ncbi.nlm.nih.gov

Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society. [2023]