Thrombolysis with Tenecteplase for Acute Ischemic Stroke in Patients taking Direct Oral Anticoagulants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Hamburg-Eppendorf

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

9 Mar 2026 → ongoing

Decision date (initial)

2025-12-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BMFTR (funding code 01KG2504 [Förderkennzeichen])

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To assess whether intravenous thrombolysis with tenecteplase 0.25 mg/kg improves functional outcome after acute ischemic stroke in patients taking direct oral anticoagulants compared to placebo.

Secondary objectives 12

1. Efficacy Objective: To assess whether intravenous thrombolysis with tenecteplase 0.25 mg/kg increases the rate of nondisabled functional outcome after acute ischemic stroke in patients taking direct oral anticoagulants compared to placebo.
2. Efficacy Objective: To assess whether intravenous thrombolysis with tenecteplase 0.25 mg/kg increases the rate of independent functional outcome after acute ischemic stroke in patients taking direct oral anticoagulants compared to placebo.
3. Efficacy Objective: To assess whether intravenous thrombolysis with tenecteplase 0.25 mg/kg reduces early neurological deficit after acute ischemic stroke in patients taking direct oral anticoagulants compared to placebo.
4. Efficacy Objective: To assess whether intravenous thrombolysis with tenecteplase 0.25 mg/kg improves physical and mental health-related quality of life after acute ischemic stroke in patients taking direct oral anticoagulants compared to placebo.
5. Efficacy Objective: To assess whether intravenous thrombolysis with tenecteplase 0.25 mg/kg reduces cognitive impairment after acute ischemic stroke in patients taking direct oral anticoagulants compared to placebo.
6. Safety Objective: To assess the rate of any intracranial haemorrhage (ICH) after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.
7. Safety Objective: To assess the rate of symptomatic intracranial haemorrhage (sICH) after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.
8. Safety Objective: To assess the rate of fatal intracranial haemorrhage after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.
9. Safety Objective: To assess the rate of major haemorrhage after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.
10. Safety Objective: To assess the rate of orolingual angioedema after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.
11. Safety Objective: To assess the rate of death or dependency after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.
12. Safety Objective: To assess mortality and survival time after intravenous thrombolysis with tenecteplase 0.25 mg/kg for acute ischemic stroke in patients taking direct oral anticoagulants.

Conditions and MedDRA coding

acute ischemic stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years
2. Clinical diagnosis of acute stroke with disabling deficit
3. National Institutes of Health Stroke Scale (NIHSS) score at least 2
4. Recent intake (within 48 hours prior to enrolment) of a direct oral anticoagulant (apixaban, rivaroxaban, edoxaban, or dabigatran)
5. No evidence of any intracranial haemorrhage on cerebral imaging (CT or MRI) performed after stroke onset and no earlier than 60 minutes before enrolment
6. Stroke symptoms not known to have been present for > 6 h
7. For patients not known to have been awake and without acute stroke symptoms within 4.5 hours prior to enrolment, additional imaging criteria must be satisfied: a) If stroke symptoms are known to have been present for > 4.5 h (late time window): core/penumbra mismatch on MR or CT perfusion imaging; b) If stroke symptoms are not known to have been present for > 4.5 h (unknown time window): core/penumbra mismatch on MR or CT perfusion imaging; or DWI/FLAIR mismatch on MR imaging.

Exclusion criteria 7

1. Contraindication to intravenous thrombolysis, except DOAC therapy
2. Reversal or planned reversal of anticoagulation with idarucizumab or andexanet alfa
3. Concomitant therapy with antithrombotic medications, except DOACs
4. Anticipated stenting of cervical or intracranial artery within 12 hours
5. Anticipated coronary angioplasty within 12 hours
6. Any anticipated surgical intervention within 12 hours
7. Significant pre-stroke disability (mRS > 3)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Functional outcome (modified Rankin Scale, mRS) 90 days after randomisation

Secondary endpoints 13

1. Efficacy Endpoint: Nondisabled (mRS score ≤ 1) functional outcome after 90 days
2. Efficacy Endpoint: Independent (mRS score ≤ 2) functional outcome after 90 days
3. Efficacy Endpoint: Early neurological deficit (National Institutes of Health stroke scale) after 24 hours
4. Efficacy Endpoint: Health-related quality of life (PROMIS®-10) after 90 days
5. Efficacy Endpoint: Cognitive impairment (Montreal Cognitive Assessment) after 90 days
6. Safety Endpoint: Any intracranial haemorrhage within 36 hours
7. Safety Endpoint: Symptomatic intracranial haemorrhage within 36 hours (mSITS-MOST)
8. Safety Endpoint: Fatal intracranial haemorrhage within 30 days
9. Safety Endpoint: Major haemorrhage (ISTH) within 72 hours
10. Safety Endpoint: Orolingual angioedema within 4 hours
11. Safety Endpoint: Death or dependency (mRS score 4–6) after 90 days
12. Safety Endpoint: All-cause mortality after 90 days
13. Safety Endpoint: Time to death right-censored at 90 days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Hamburg-Eppendorf

Sponsor organisation

University Medical Center Hamburg-Eppendorf

Address

Martinistrasse 52, Eppendorf Eppendorf

City

Hamburg

Postcode

20246

Country

Germany

Scientific contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Senior Physician at the Department of Neurology

Public contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Senior Physician at the Department of Neurology

Third parties 7

Locations

1 EU/EEA country · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications