Intravenous Thrombolysis and NOAC

Phase 3

Recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: Intravenous thrombolysis

• Registration Number: NCT06749834
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

New oral anticoagulants (NOACs), including rivaroxaban, apixaban, dabigatran, and edoxaban, have become the first-line therapy for preventing ischemic stroke associated with non-valvular atrial fibrillation (NVAF). Despite the effectiveness of NOACs in preventing thromboembolic events, approximately 1% to 2% of patients taking NOACs experience an ischemic stroke annually. Intravenous thrombolysis is an important means of treating acute ischemic stroke (AIS). However, due to concerns about the risk of symptomatic intracranial hemorrhage (sICH) or other severe bleeding complications, current guidelines still consider the use of NOACs within 48 hours before symptom onset as a contraindication to intravenous thrombolysis. Epidemiological data suggest that this may result in up to 18% of AF patients being unable to receive intravenous thrombolysis when they have an AIS episode.

Previous animal experiments have shown that NOACs do not increase the risk of hemorrhagic transformation after intravenous thrombolysis. Pharmacokinetic studies have demonstrated that 24 to 48 hours after taking NOACs, the anti-Xa level in patients is relatively low (\<0.5 U/mL). In recent years, multiple retrospective studies and meta-analyses have shown that prior use of NOACs does not increase the risk of sICH in AIS patients receiving intravenous thrombolysis, and there are no significant differences in functional outcomes at 3 months. With solid pharmacokinetic and retrospective clinical evidence to support, it is hypothesized that IVT are safe in IS-NOAC patient. The investigators hereby propose a prospective multicenter study to determine the efficacy and safety of IVT in acute IS-NOAC.

Detailed Description

In this prospective cohort study, the investigators aim to recruit consecutive IS-NOAC patients who met the inclusion criteria. The investigators sought to determine the safety and efficacy of IVT in acute ischemic stroke patients on NOACs. It is hypothesized that for IS-DOAC patients with the last intake of NOAC within 48 hours, IVT improved neurological outcomes with acceptable safety compared to a cohort of acute IS-NOAC patients excluded from IVT.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-15
• Study First Submitted QC: 2024-12-23
• Study First Posted: 2024-12-27
• Study Start: 2025-01-27
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-24
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

1. Patients with clinical signs of acute ischemic stroke within 24 hours of onset or awakening with stroke (if within 24 hours from the midpoint of sleep). Patients with AIS within 4.5-24 hours of onset must meet the IVT inclusion criteria specified in the guideline
2. Patients with new oral anticoagulants usage within 4-48 hours of onset;
3. Patients ≥ 18 years old
4. Informed consent has been obtained depending on local ethics requirements.

Exclusion Criteria

1. Intended to proceed to endovascular treatment
2. With APTT >40s
3. Pre-stroke mRS score > 2
4. Contraindications for IVT：

1. Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hematoma, etc.) 2) Previous history of intracranial hemorrhage 3) Severe head trauma or stroke history within the last 3 months 4) Intracranial tumors, giant intracranial aneurysms 5) Intracranial or spinal surgery within the recent 3 months 6) Major surgical procedures within the last 2 weeks 7) Gastrointestinal or urinary tract bleeding within the last 3 weeks 8) Active visceral bleeding 9) Aortic arch dissection 10) Arterial puncture in a site within the last 1 week that is not easy to compress and stop bleeding 11) Elevated blood pressure: Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg 12) Acute bleeding tendency, including platelet count < 100 × 10⁹/L or other conditions 13) Received low-molecular-weight heparin treatment within 24 hours 14) Oral anticoagulants (warfarin) with INR > 1.7 or PT > 15 s 15) Blood sugar < 2.8 or > 22.22 mmol/L 16) Head CT or MRI indicates large-area infarction (infarction area ≥ 1/3 of the middle cerebral artery supply area) (4) The judgment is left to the discretion of the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous thrombolysis	Intravenous thrombolysis	Patients will receive standard dose intravenous alteplase (0.9 mg/kg, the first 10% administered as an initial bolus and the remainder over a 1-hour period, with a maximum dose of 90 mg)，intravenous Tenecteplase(0.25mg/kg，administered as a single intravenous bolus injection over 5 - 10 seconds，with a maximum dose of 25 mg), intravenous reteplase (a bolus of 18 mg followed by a second bolus of 18 mg after 30 minutes) and intravenous prourokinase (rhPro-UK) (15 mg bolus followed by a 20 mg infusion over 30 minutes).

Primary Outcome Measures

Name	Time	Method
Excellent recovery assessed by the ratio of modified Rankin Scale (mRS) score of 0-1 (%) at 90 ± 7 days	90 ± 7 days	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome

Secondary Outcome Measures

Name	Time	Method
the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day	from baseline to 1 day	NIHSS: minimum value = 0, maximum value = 42, and higher scores mean severer symptoms
Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 90 ± 7 days	90 ± 7 days	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
recovery assessed by modefied Rankin Scale (mRS) score	90 ± 7 days	mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome
3-month mortality	90 ± 7 days	Hospitalization records or follow-up results
Presence of parenchymal hemorrhage (PH)	at day 1	the presence of PH is defined according the standard from ECASS-2 study
Presence of symptomatic intracerebral hemorrhage (sICH)	at day 1	the presence of sICH is defined according the standard from ECASS-2 study
Presence of hemorrhagic transformation	at day 1	Presence of hemorrhagic transformation is defined according the standard from ECASS-2 study

Trial Locations

Locations (2)

The First People's Hospital of Wenling; 🇨🇳 Taizhou, Zhejiang, China

Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou; 🇨🇳 Hangzhou, Zhejiang, China