Tenecteplase for Stroke

(DoubleDoseTNK Trial)

Overseen By Alexandra L Czap, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Hermann Health System

Must not be taking: Antiplatelets, Amyloid therapy, Anticoagulants

Disqualifiers: LVO, MeVO, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you cannot be on more than one antiplatelet agent within 48 hours prior to enrollment, and you must not have used certain blood thinners like warfarin or direct oral anticoagulants within specified time frames before joining the trial.

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

Research shows that Tenecteplase can lead to better early neurological improvement compared to another drug, alteplase, in patients with acute ischemic stroke. It is also noted for its practical advantages and similar safety outcomes. ^{1 2 3 4 5}

Is tenecteplase safe for use in humans?

Tenecteplase has been studied for safety in treating acute ischemic stroke and is generally considered as safe as alteplase, another stroke treatment. However, in patients with severe strokes, there was a higher mortality rate at 90 days with tenecteplase, so safety should be monitored closely in these cases. ^{6 7 8 9 10}

How does the drug Tenecteplase differ from other treatments for stroke?

Tenecteplase is unique because it is a genetically modified drug that can be given as a single injection, making it more convenient than alteplase, which requires a longer infusion. It also has a higher specificity for fibrin (a protein involved in blood clotting) and a longer half-life, potentially leading to better outcomes in large vessel occlusions without increasing the risk of bleeding. ^{3 11 12 13 14}

What is the purpose of this trial?

In this pilot safety study, the investigators will give a second dose of Intravenous Tenecteplase (IV TNK) to patients receiving the initial TNK dose within 3 hrs of last known normal (LKN), have a baseline National Institutes of Health Stroke Scale (NIHSS) \> 6, and who do not clinically improve within 45 minutes of the first dose, or who improve but then deteriorate, and can still be treated within 4.5 hours from LKN. Patients will require a second computed tomography (CT) scan to rule out any bleeding, and meet the usual inclusion and exclusion criteria for TNK treatment, before the second dose which must be given within 4.5 hrs of LKN. Both TNK doses will be 0.25 mg/kg. The initial TNK dose may be given on the Mobile Stroke Unit (MSU) or Emergency Department (ED), and the second dose in the ED. Informed consent will be obtained before the second dose is given. The primary outcome will be symptomatic intracranial hemorrhage (sICH) (SITS-MOST criteria) or serious systemic bleeding within 36 hours. Secondary outcomes will be any intracranial hemorrhage, any bleeding, discharge NIHSS and modified Rankin Score (mRS), and mRS at 90 days (sliding dichotomy). 20 patients will be enrolled. Enrollment will be stopped if more than 3 sICH occur (\> 80% confidence that sICH rate is \> 5%. If successful, this study will be followed by a larger phase 2b controlled safety confirmation and pilot efficacy study,

Eligibility Criteria

This trial is for acute ischemic stroke patients who haven't improved after a first dose of Tenecteplase within 3 hours from symptom onset, have an NIHSS score over 6, and can receive a second dose within 4.5 hours. They must not show bleeding on a CT scan and meet standard criteria for Tenecteplase.

Inclusion Criteria

NIHSS > 6 for both first and second dose

Time from LKN < 3 hrs (first dose) and < 4.5 hours (second dose)

Patient/legally authorized representative has signed the Informed Consent Form

Exclusion Criteria

I am scheduled for a clot removal procedure before my second dose of TENECTEPLASE.

I have a bleeding disorder.

I've used heparin recently and my blood test shows slower clotting.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Initial Treatment

Participants receive the first dose of IV Tenecteplase within 3 hours of last known normal

Immediate

1 visit (in-person)

Second Dose Administration

Participants receive a second dose of IV Tenecteplase if they do not improve within 45 minutes of the first dose or deteriorate after initial improvement

Within 4.5 hours of last known normal

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neuro checks and NIHSS assessments

90 days

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Tenecteplase

Trial Overview The study tests the safety of giving a second dose of Tenecteplase to stroke patients who don't respond to the initial treatment. It measures severe bleeding risks and changes in neurological status immediately after treatment and at follow-up.

Participant Groups

Group I: Patients receiving double dose TNK Experimental Treatment 1 Intervention

The investigators will give a second dose of IV TNK to patients receiving the initial TNK dose within 3 hrs of LKN, have a baseline NIHSS \> 6, and who do not clinically improve within 45 minutes of the first dose, or who improve but then deteriorate, and can still be treated within 4.5 hours from LKN. Patients will require a second CT scan to rule out any bleeding, and meet the usual inclusion and exclusion criteria for TNK treatment, before the second dose which must be given within 4.5 hrs of LKN. Both TNK doses will be 0.25 mg/kg. The initial TNK dose may be given on the MSU or ED, and the second dose in the ED.

Who Is Running the Clinical Trial?

Memorial Hermann Health System

Lead Sponsor

Trials

10

Recruited

2,002,000+

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

Grotta Stroke Research Foundation

Collaborator

Trials

1

Recruited

20+

Memorial Hermann Hospital Mobile Stroke Unit

Collaborator

Trials

1

Recruited

20+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

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.

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 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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase in acute ischemic stroke: systematic review and meta-analysis. [2020]

2. India pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of tenecteplase versus alteplase for stroke thrombolysis evaluation trial in the ambulance. [2023]

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

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

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

Early Experience With Tenecteplase at a Comprehensive Stroke Center. [2022]

6. 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]

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. England pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

Safety and Outcomes of Tenecteplase in Moderate and Severe Ischemic Stroke. [2020]

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

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

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

Evolving Thrombolytics: from Alteplase to Tenecteplase. [2023]

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

Tenecteplase Thrombolysis for Acute Ischemic Stroke. [2021]

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

Moving From Alteplase to Tenecteplase for Acute Ischemic Stroke-Mayo Clinic Experience. [2023]