Intravenous Thrombolysis and NOAC

NCT ID: NCT06749834

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-27
• Study Completion Date: 2027-06-30

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.

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: EXPERIMENTAL

Intravenous thrombolysis

Intervention Type: DRUG

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).

Standard therapy

Standard therapy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou

Hangzhou, Zhejiang, China

Site Status: NOT_YET_RECRUITING

The First People's Hospital of Wenling

Taizhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Min Lou, PhD, MD

Role: CONTACT

lm99@zju.edu.cn

8613958007213

Wansi Zhong, MD

Role: CONTACT

21718233@zju.edu.cn

8618757155806

Facility Contacts

Min Lou, PhD, MD

Role: primary

lm99@zju.edu.cn

8613958007213

Wansi Zhong, MD

Role: backup

21718233@zju.edu.cn

8618757155806

Hinlong Huo

Role: primary

jaydenhuo@163.com

8615958755756

Other Identifiers

I-NOAC

Identifier Type: -

Identifier Source: org_study_id