Efficacy and Safety of Tenecteplase Among acutE Ischemic Stroke Patients With Recent Ingestion of Direct Oral Anticoagulant

NCT07621796 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: ESTER-DOAC
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Ischemic Stroke

Keywords

acute ischemic stroke; Oral AntiCoagulants; thrombolysis; intravenous tenecteplase administration

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Patients with excellent functional outcome

  90 days post administration

• Patients with good functional outcome

  90 days post administration

• Utility weighted mRS between intravenous TNK versus placebo

  90 days post administration

Study Arms (2)

Intravenous Tenecteplase (TNK)

EXPERIMENTAL

Intravenous TNK 0.25 mg/Kg

Drug: Intravenous tenecteplase (TNK)

Placebo

PLACEBO COMPARATOR

normal saline placebo

Drug: Placebo

Interventions

Intravenous tenecteplase (TNK) DRUG

Intravenous administration of tenecteplase (TNK) at 0.25 mg/kg for a maximum dose of 25 mg.

Intravenous Tenecteplase (TNK)

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

Hackensack Meridian Health - Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Shadi Yaghi, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle Dubenezic

CONTACT

732-897-8175; danielle.dubenezic@hmhn.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: June 2, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 30, 2032
• Study Completion (Estimated): January 30, 2032
• Last Updated: June 2, 2026

Record last verified: 2026-05

Locations

US (1)