Clinical trial NCT06749834: Intravenous Thrombolysis and NOAC
Official title: Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on New Oral Anticoagulants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: Intravenous thrombolysis
outcome
NOAC
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2024-12-27
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Excellent recovery assessed by the ratio of modified Rankin Scale (mRS) score of 0-1 (%) at 90 ± 7 days
timeFrame: 90 ± 7 days
Secondary outcomes:
measure: the change on the National Institute of Health stroke scale (NIHSS) score from baseline to 1 day
timeFrame: from baseline to 1 day
measure: Independent recovery assessed by ratio of modefied Rankin Scale (mRS) score of 0-2 (%) at 90 ± 7 days
timeFrame: 90 ± 7 days
measure: recovery assessed by modefied Rankin Scale (mRS) score
timeFrame: 90 ± 7 days
measure: 3-month mortality
timeFrame: 90 ± 7 days
measure: Presence of parenchymal hemorrhage (PH)
timeFrame: at day 1
measure: Presence of symptomatic intracerebral hemorrhage (sICH)
timeFrame: at day 1
measure: Presence of hemorrhagic transformation
timeFrame: at day 1
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou
state: Zhejiang
city: Taizhou
country: China
facility: The First People's Hospital of Wenling
state: Zhejiang
Study officials:
References: