Efficacy and Safety of Tenecteplase Among acutE Ischemic Stroke Patients With Recent Ingestion of Direct Oral Anticoagulant (ESTER-DOAC)

Efficacy and Safety of Tenecteplase Among acutE Ischemic Stroke Patients With Recent Ingestion of Direct Oral Anticoagulant (ESTER-DOAC)

The study will randomize patients with acute ischemic stroke and Direct Oral AntiCoagulants (DOAC) ingestion within 48 hours from enrollment (but otherwise eligible for thrombolysis) to administration of intravenous tenecteplase vs. placebo (1:1).

Participants will be enrolled at NIH StrokeNet sites across the US and followed for 90-days.

The primary aim is to determine the efficacy of intravenous tenecteplase (TNK) vs placebo among acute ischemic stroke patients and to determine the safety of TNK among acute ischemic stroke patients within 4.5 hours of last known well who used DOAC within 48 hours prior to thrombolysis. Efficacy and safety endpoints will be the focus of this proposed Phase III study.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Placebo; Drug: Intravenous tenecteplase (TNK)

• Study Type: Interventional
• Enrollment (Estimated): 660
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Danielle Dubenezic; Phone Number: 732-897-8175; Email: danielle.dubenezic@hmhn.org

Study Locations

• United States
  • New Jersey
    • Neptune City, New Jersey, United States, 07753
      • Hackensack Meridian Health - Jersey Shore University Medical Center
      • Principal Investigator: Shadi Yaghi, MD
      • Contact: Danielle Dubenezic; Phone Number: 732-897-8175; Email: danielle.dubenezic@hmhn.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults (18 years or older) with a suspected acute ischemic stroke and clearly disabling deficits
• Presenting within 4.5 hours of last known well
• Able to initiate intravenous thrombolysis within 4.5 hours of last known well
• On recent DOAC therapy (dabigatran, apixaban, rivaroxaban, edoxaban) and known last dose taken within 48 hours from thrombolysis.

Exclusion Criteria:

• Current or history of intracerebral hemorrhage
• Non-disabling deficits
• Bleeding disorder (e.g. hemophilia) or advanced liver disease or known INR > 1.7 within 6 hours
• Use of therapeutic low molecular weight heparin or therapeutic dose heparin with elevated PTT
• ASPECTS < 6 or clear hypodensity on CT suggestive of completed infarct
• Advanced kidney disease (eGFR < 30 ml/min)
• Known or suspected aortic dissection
• Known or high suspicion for infective endocarditis
• Surgery within 2 weeks
• Intracranial or intraspinal surgery within 3 months
• Active internal bleeding or gastrointestinal or urinary tract hemorrhage within 3 weeks
• Intracranial neoplasm, arterio-venous malformation, or cavernous malformation
• Major head trauma or ischemic stroke within 3 months
• Known thrombocytopenia (platelets < 100,000)
• Planned endovascular treatment within 30 minutes of study drug administration (i.e., consent, randomization and administration of study drug must occur at least 30 minutes prior to groin puncture; standard care is not to be delayed and patients in whom endovascular therapy will start sooner will not be enrolled)
• Comorbid condition with life expectancy of less than 3 months
• Any condition that precludes thrombolytic therapy as determined by site principal investigator
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Tenecteplase (TNK); Intravenous TNK 0.25 mg/Kg	Drug: Intravenous tenecteplase (TNK); Intravenous administration of tenecteplase (TNK) at 0.25 mg/kg for a maximum dose of 25 mg.
Placebo Comparator: Placebo; normal saline placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of intravenous Tenecteplase (TNK)	Determine the efficacy of intravenous Tenecteplase (TNK) vs placebo among acute ischemic stroke patients within 4.5 hours of their last known well who used DOAC within 48 hours prior to thrombolysis. The primary endpoint is 90-day modified Rankin Scale (mRS). Modified Rankin Scale is a 6 point tool to assess disability with 0 being no disability and 6 being death.	90 days post administration
Safety of intravenous TNK	Determine the safety of intravenous TNK among acute ischemic stroke patients within 4.5 hours of last known well who used DOAC within 48 hours prior to thrombolysis. The primary safety endpoint is symptomatic intracranial hemorrhage (sICH) sICH is defined as any hemorrhage with neurological deterioration in the form of ≥ 4 points increase in the NIHSS, or that leads to death and is identified as the predominant cause of the neurologic deterioration (ECASS III definition) and occurring within 36 hours from thrombolysis administration	within 36 hours from thrombolysis administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with excellent functional outcome	To compare the percentage of patients with excellent functional outcome (mRS 0-1) between intravenous TNK versus placebo. mRS 0-1 at 90-days The endpoint of mRS 0-1 at 90 days is a standard outcome used in stroke trials to measure functional improvements after acute treatments such as thrombolysis and endovascular treatment	90 days post administration
Patients with good functional outcome	To compare the percentage of patients with good functional outcome (mRS 0-2) between intravenous TNK versus placebo. mRS 0-2 at 90-days The endpoint of mRS 0-2 at 90 days is a standard outcome used in stroke trials to measure functional improvements after acute treatments such as thrombolysis and endovascular treatment	90 days post administration
Utility weighted mRS between intravenous TNK versus placebo	To compare the utility weighted mRS between intravenous TNK versus placebo. Utility weighted mRS The endpoint of Utility mRS at 90 days is a standard outcome used in stroke trials to measure functional improvements after acute treatments such as thrombolysis and endovascular treatment	90 days post administration

Collaborators and Investigators

• Sponsor: Hackensack Meridian Health
• Investigators: Principal Investigator: Shadi Yaghi, MD, Hackensack Meridian Health

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 30, 2032
• Study Completion (Estimated): January 30, 2032

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: thrombolysis; acute ischemic stroke; Oral AntiCoagulants; intravenous tenecteplase administration
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: ESTER-DOAC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No