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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of administering Tenecteplase directly to the artery in individuals who have had a blood clot removed from the brain due to a stroke. Typically, Tenecteplase is given intravenously, but this trial evaluates its safety and efficacy when delivered intra-arterially. Participants should have experienced a recent stroke caused by a blocked blood vessel and undergone a clot removal procedure. Those with frequent high blood pressure or recent strokes might not be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

Is there any evidence suggesting that intra-arterial Tenecteplase is likely to be safe for humans?

Research has shown that Tenecteplase, when delivered directly into an artery, has been studied for treating strokes caused by large blocked blood vessels. Results indicate that this treatment can open these blockages without increasing bleeding risk. Another study found that Tenecteplase improved blood flow after clot removal without causing additional side effects. The FDA has already approved Tenecteplase for use in stroke patients within the first 3 hours, providing some reassurance about its safety in humans.

In these studies, patients generally tolerated Tenecteplase well, experiencing few serious side effects. This evidence supports its safety in stroke treatment. However, discussing potential risks with a healthcare provider is always important when considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke?

Researchers are excited about intra-arterial Tenecteplase for stroke because it offers a novel delivery method targeting clots directly, which could enhance its effectiveness. Unlike standard treatments like intravenous thrombolytics, this method delivers the drug precisely to the clot site via a microcatheter, potentially reducing the time it takes to restore blood flow in the brain. Additionally, Tenecteplase itself is a powerful clot-busting agent designed to break down clots more effectively than some current options. This targeted approach and potent action could mean quicker recovery times and better outcomes for stroke patients.

What evidence suggests that intra-arterial Tenecteplase could be an effective treatment for stroke?

Research shows that using Tenecteplase directly in the arteries after removing blood clots may help treat strokes caused by major blockages. In this trial, participants will receive either intra-arterial Tenecteplase or a saline placebo following endovascular thrombectomy. Studies have found that Tenecteplase can improve blood flow in the brain after clot removal, which is important for recovery. Specifically, one study found that patients who received Tenecteplase in this way had better results than those who did not. Another study demonstrated that Tenecteplase is effective if used within 24 hours of the first stroke symptoms, a crucial treatment window. While more research is ongoing, these findings suggest that Tenecteplase could be a promising option for stroke patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Rahul Karamchandani, MD

Principal Investigator

Atrium Health Neurosciences Institute

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2836176

Intra-Arterial Tenecteplase After Successful Reperfusion in ... Safety and efficacy of adjunctive intra-arterial tenecteplase following successful thrombectomy in patients with large vessel occlusion: a phase 1/2 randomized ...

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.125.052511

The ETERNAL-LVO Randomized Controlled Trial | Stroke Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12228979/

Intra-Arterial Tenecteplase After Successful Reperfusion in ... This phase 1 and 2 randomized clinical trial investigated both the safety threshold and efficacy of 3 different doses of tenecteplase when ...

4. jnis.bmj.com jnis.bmj.com/content/early/2025/10/23/jnis-2025-024129

Occlusion site and outcomes in intra-arterial tenecteplase ... Intra-arterial (IA) tenecteplase shows potential for large vessel occlusion (LVO) stroke, but prior research did not stratify its efficacy/ ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586825006435

Efficacy and safety of adjunctive intra-arterial tenecteplase ... Efficacy and safety of adjunctive intra-arterial tenecteplase following endovascular thrombectomy for large vessel occlusion acute ischemic stroke: a systematic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39804681/

The POST-TNK Randomized Clinical Trial Objective: To assess the efficacy and adverse events of adjunctive intra-arterial tenecteplase in patients with large vessel occlusion stroke ...

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.031692

Comprehensive Review of Tenecteplase for Thrombolysis ... Tenecteplase has been suggested to improve recanalization and reperfusion without increasing the risk of hemorrhage and may lyse large vessel clots more ...