Tenecteplase IV thrombolysis for acute ischemic stroke after recent DOAC use

Tenecteplase for Intravenous Stroke Thrombolysis in Recent DOAC Users (PEARL-DOAC): A Multicenter, Prospective, Randomized, Double-blinded, Placebo-controlled Trial

This will test whether a single IV dose of tenecteplase can improve 90-day recovery in adults who have an acute ischemic stroke and took a direct oral anticoagulant within the past 48 hours.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 912 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: Idarucizumab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07092709 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, double-blind, placebo-controlled Phase 3 trial will enroll about 912 adults with acute ischemic stroke who took a DOAC within 48 hours or whose DOAC timing is unknown. Participants are randomized 1:1 to a single IV bolus of tenecteplase (0.25 mg/kg, max 25 mg) or matched placebo in addition to standard care, with treatment given within 4.5 hours of last known well or within 4.5–24 hours if perfusion imaging shows a target mismatch. The primary outcome is the proportion of patients achieving a favorable 90-day functional outcome (modified Rankin Scale 0–1), and safety endpoints include symptomatic intracerebral hemorrhage and mortality. Enrollment limits the proportion of patients with DOAC intake 24–48 hours or unknown timing to 50% and may restrict inclusion to DOAC intake within 24 hours if that cap is reached.

Who should consider this trial

Good fit: Adults with acute ischemic stroke who received a DOAC within 48 hours (or have unknown timing), who can be treated within 4.5 hours of last known well or within 4.5–24 hours with a perfusion mismatch, and who have no contraindications to thrombolysis.

Not a fit: Patients with large ischemic cores (>50 mL), those outside the treatment windows without a perfusion mismatch, or those with contraindications or high bleeding risk are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could allow more people on DOACs to safely receive IV thrombolysis and reduce long-term disability after stroke.

How similar studies have performed: Prior trials and meta-analyses have shown tenecteplase to be at least as effective as alteplase for ischemic stroke, but randomized data specifically in recent DOAC users are limited.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Yamei Tang — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Yanting Chen

Conditions Acute Ischemic Stroke