Intravenous Thrombolysis and NOAC

NCT06749834 | Recruiting Phase 3 DMC

• 1 other identifier: I-NOAC
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Ischemic Stroke

Keywords

Intravenous thrombolysis; outcome; NOAC

Outcome Measures

Primary Outcomes (1)

• Excellent recovery assessed by the ratio of modified Rankin Scale (mRS) score of 0-1 (%) at 90 ± 7 days

  mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome

  90 ± 7 days

Secondary Outcomes (7)

• the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day

  from baseline to 1 day

• Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 90 ± 7 days

  90 ± 7 days

• recovery assessed by modefied Rankin Scale (mRS) score

  90 ± 7 days

• 3-month mortality

  90 ± 7 days

• Presence of parenchymal hemorrhage (PH)

  at day 1

Study Arms (2)

Intravenous thrombolysis

EXPERIMENTAL

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).

Drug: Intravenous thrombolysis

Standard therapy

NO INTERVENTION

Standard therapy

Interventions

Intravenous thrombolysis 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).

Intravenous thrombolysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with new oral anticoagulants usage within 4-48 hours of onset;
• Patients ≥ 18 years old
• Informed consent has been obtained depending on local ethics requirements.

You may not qualify if:

• Intended to proceed to endovascular treatment
• With APTT \>40s
• Pre-stroke mRS score \> 2
• Contraindications for IVT：
• \) 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

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (2)

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

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

The First People's Hospital of Wenling

Taizhou, Zhejiang, 317500, China

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Min Lou, PhD, MD

CONTACT

8613958007213; lm99@zju.edu.cn

Wansi Zhong, MD

CONTACT

8618757155806; 21718233@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2024
• First Posted: December 27, 2024
• Study Start: January 27, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: February 24, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)