Tenecteplase for Intravenous Stroke Thrombolysis in Recent DOAC Users

Not Applicable

Not yet recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg); Drug: Placebo

• Registration Number: NCT07092709
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

An investigator-initiated, multicenter, randomized, placebo-controlled, double-blind trial to determine the efficacy and safety of intravenous tenecteplase thrombolysis in acute ischemic stroke (AIS) patients with recent direct oral anticoagulants (DOACs) intake in improving the 90-day functional outcome.

Detailed Description

This study is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of intravenous tenecteplase thrombolysis in AIS patients with recent DOACs intake 48 hours prior to enrollment. The primary outcome is the proportion of patients with a 90-day modified Rankin scale (mRS) of 0-1.

Study intervention: (1) Participants in the intervention group will receive tenecteplase administered as a single intravenous bolus at a dose of 0.25 mg/kg, with a maximum of 25 mg, administered as soon as possible after the randomization. (2) Participants in the control group will receive matched intravenous placebo in the same approach. All participants will receive standard medical treatment.

A total of 912 participants are anticipated to be recruited for this study, with 456 participants in each group (1:1 ratio).

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-22
• Study First Submitted QC: 2025-07-22
• Last Update Submitted: 2025-07-22
• Study First Posted: 2025-07-30
• Last Update Posted: 2025-07-30
• Study Start: 2025-08-01
• Primary Completion: 2028-09-01
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 912

Inclusion Criteria

1. Age 18 years or older.

2. Clinically diagnosed with acute ischemic stroke.

3. DOACs intake within 48 hours prior to enrollment, or on an ongoing DOACs therapy but the exact time of last intake is unknown.

   • To ensure a representative study population, the investigators will limit the number of patients who took DOACs within 24-48 hours before enrollment or those with unknown last intake time to 50% of the planned sample size. If this number is reached, the inclusion criterion 3 will be modified:

   DOACs intake within 24 hours prior to enrollment.

4. Study intervention (IVT or placebo) can be started

   1. within 4.5 hours of last known well (LKW). OR

   2. within 4.5 to 24 hours of LKW (including wake-up stroke) AND evidence of target mismatch profile on CT perfusion or MR perfusion (ischemic core volume < 50mL, hypoperfused volume to ischemic core volume ratio > 1.6, mismatch volume ≥10ml).

      • Hypoperfused tissue is defined as Tmax >6s on CT perfusion or MR perfusion. Ischemic core is defined as rCBF <30% on CT perfusion or ADC<620μm^2/s on diffusion MRI.

5. Baseline National Institutes of Health Stroke Scale (NIHSS) 4-25. OR Disabling stroke with baseline NIHSS of 0-3, including complete hemianopia, aphasia, measurable deficit on motor power, or other disabling neurological deficit judged by the investigator.

6. Written informed consent signed by patients or their legally authorized representatives.

Exclusion Criteria

1. Intracranial or subarachnoid hemorrhage confirmed by cranial computed tomography (CT) or magnetic resonance imaging (MRI), or any intracranial hemorrhage history.
2. Allergic to tenecteplase.
3. Pre-stroke mRS≥2
4. Planned endovascular treatment.
5. Currently on dual antiplatelet therapy in addition to DOAC therapy.
6. Planned DOAC reversal treatment (including Idarucizumab, Andexanet and tranexamic acid).
7. Hypodensity on non-contrast CT estimates to be ≥ 1/3 MCA territory.
8. Severe head trauma or other severe trauma in the last 3 months.
9. Intracranial tumor, arteriovenous malformation and large-size aneurysm (≥10 mm) found before enrollment.
10. Intracranial surgery, intraspinal surgery or other major surgeries within 3 months before enrollment (based on the assessment of the investigators)
11. Gastrointestinal or urinary system hemorrhage within the past 3 weeks.
12. Active visceral bleeding.
13. Aortic arch dissection confirmed by examination or medical history.
14. Infective endocarditis confirmed by examination or medical history.
15. Platelet count less than 100 × 10^9 /L.
16. Patients received heparin or low-molecular-weighted heparin treatment within 24h before enrollment.
17. Pregnant or lactating women.
18. Blood glucose <50 mg/dl (2.78mmol/L) or >400 mg/dl (22.2mmol/L) during screening.
19. Uncontrolled hypertension with persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, refractory to medical management.
20. Life expectancy less than 6 months due to malignancy, severe cardiopulmonary disease, or other terminal illness.
21. Participating in other trials.
22. Other conditions deemed unsuitable for the study by the investigator, such as inability to comprehend or comply with study procedures or follow-up due to mental illness, cognitive or emotional disorder.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous tenecteplase	Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg)	-
Matched placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
The modified Rankin Scale score (mRS) 0-1	90 (±14) days	The proportion of mRS score 0-1 at 90 (±14) days.

Secondary Outcome Measures

Name	Time	Method
Level of disability	90 (±14) days	The shift analysis of the 90-day mRS with 5-6 merged at 90 (±14) days.
The modified Rankin Scale score (mRS) 0-2	90 (±14) days	The proportion of mRS score 0-2 at 90 (±14) days.
The proportion of NIHSS 0-1 or ≥4 points reduction	24 (±12) hours	The proportion of NIHSS 0-1 or ≥4 points reduction at 24 (±12) hours.
Neurologic deficit (NIHSS score) changes	7 (±1) days or at discharge	Neurologic deficit (NIHSS score) changes from baseline to 7 (±1) days or at discharge if earlier.
The modified Rankin Scale score (mRS) 0-3	90 (±14) days	The proportion of mRS score 0-3 at 90 (±14) days
Quality of life (EQ-5D-5L)	90 (±14) days	Quality of life measured by EQ-5D-5L scale score at 90 (±14) days.

Trial Locations

Locations (1)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China