Safety Of A Second Dose Of Tenecteplase In Selected Acute Ischemic Stroke Patients Not Responding To The First Dose

NCT06801054 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: Double Dose TNKML45872
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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,

Conditions

Acute Ischemic Stroke

Keywords

stroke; tenecteplase; mobile stroke unit; acute ischemic stroke

Outcome Measures

Primary Outcomes (1)

• The number of patients with symptomatic intracerebral hemorrhage or major systemic bleeding

  A type 2 parenchymal hemorrhage or a parenchymal hemorrhage remote from the area of infarction with neurological deterioration (≥4-point worsening in National Institutes of Health Stroke Scale) and major hemorrhage (requiring \>2 units packed red blood cells)

  within 36 hours of enrollment (2nd dose of tenecteplase)

Secondary Outcomes (1)

• Clinical efficacy outcome

  90 days post stroke

Study Arms (1)

Patients receiving double dose TNK

EXPERIMENTAL

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.

Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg)

Interventions

Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg) DRUG

All patients will receive a second dose of tenecteplase.

Patients receiving double dose TNK

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signs and symptoms suggestive of acute ischemic stroke
• Age \> 18 and \< 80 years
• Time from LKN \< 3 hrs (first dose) and \<4.5 hours (second dose)
• NIHSS \> 6 and (for both first and second dose)
• CT at baseline and prior to second dose shows no evidence of intracranial hemorrhage and has an ASPECTS score \> 6
• Patient/legally authorized representative has signed the Informed Consent Form

You may not qualify if:

• Patients with LVO or MeVO for whom EVT is intended at any time before the second dose of TENECTEPLASE
• At the time of the second dose, NIHSS is \< 6
• Systolic blood pressure \> 180 at the time of either dose of TENECTEPLASE
• Pre-stroke mRS \> 2
• Patients receiving more than one antiplatelet agent during the 48 hours prior to enrollment
• Active internal bleeding
• Patients with undiagnosed significant cognitive impairment or known cerebral amyloid angiopathy
• Patients taking lecanemab, donanemab, or other amyloid reduction therapy
• Known bleeding diathesis
• Recent use of heparin with PTT \> control
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; known administration of warfarin within 24 hours or suspected use and INR \> 1.5.
• Use of one of the direct oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
• Treatment with a thrombolytic within the last 3 months prior to enrollment
• Baseline platelet count \< 100,000/μL (results must be available prior to treatment)
• Baseline blood glucose \> 400 mg/dL (22.20 mmol/L)

Sponsors & Collaborators

• Memorial Hermann Health System: lead
• Grotta Stroke Research Foundation: collaborator
• Memorial Hermann Hospital Mobile Stroke Unit: collaborator
• The University of Texas Health Science Center, Houston: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Central Study Contacts

James c Grotta, MD

CONTACT

713 704 3953; james.grotta@memorialhermann.org

Alexandra L Czap, MD

CONTACT

713 704 3953; alexandra.l.czap@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Stroke Research and Mobile Stroke Unit

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: January 30, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: June 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 1 year after study completion (start date), 5 years after study completion (end date)
• Access Criteria: Any academic investigator upon written request to the principal investigator

Locations

US (1)