Clinical trial NCT06115070: Intravenous Thrombolytic Therapy for Acute Ischemic Stroke Patients with Low NIHSS and Non-disabling Deficits
Official title: Intravenous Thrombolytic Therapy for Acute Ischemic Stroke Patients with Low NIHSS and Non-disabling Deficits
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Thrombosis
Acute Ischemic Stroke (AIS)
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2023-11-02
Enrollment: 390
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: Minor stroke is considered an acute ischemic stroke (AIS) that has a National Institute of Health Stroke Scale (NIHSS) score ≤ 5 points. About 1/3 patients with mild stroke have poor prognosis, whether patients with this type undergo thrombolysis has been a controversial issue. A pooled analysis published in the Lancet in 2014 included 9 high-quality RCT studies of intravenous thrombolysis such as NINDS and IST3, and a total of 666 (10%) patients with mild stroke were included in the analysis. For mild stroke, the proportion of good prognosis in the control group and the alteplase group was 58.9% and 68.7% (OR 1.48, 95%Cl 1.07-2.06), respectively. Therefore, guidelines recommended alteplase thrombolytic therapy for patients with mild stroke. However, PRISMS, a randomized controlled trial of intravenous thrombolytic therapy for mild stroke published in 2018, found that alteplase intravenous thrombolytic therapy did not improve clinical outcomes compared with aspirin in patients with mild non-disabled stroke (90-day mRS 0-1 ratio 78.2% vs 81.5%), and the incidence of symptomatic intracranial hemorrhage was higher. However, a major limitation of the PRISMS study was that more than 85% of patients had numbness and dysarticulation, so this conclusion cannot be extrapolated to patients with other mild stroke symptoms. Moreover, due to the early termination of the sponsorship of this trial, the number of enrolled cases did not reach the pre-designed number, resulting in a serious decline in the authenticity of the study results. Symptoms and outcomes of minor stroke are important criteria for assessment. However, there is currently no uniform standard for the assessment of disability.

Both international and domestic guidelines recommend IVT with alteplase for minor disabling stroke within 4.5h, but not routinely recommend intravenous thrombolysis for minor nondisabling stroke within 4.5h. It is important to underline that strokes with low NIHSS scores are not necessarily nondisabling. Despite, patients with mild stroke symptoms are often excluded from IVT due to safety concerns potentially outweighing the putative benefits of recanalization therapy.

Therefore, the investigators developed a new definition to refine the disability assessment of stroke symptoms. The purpose of this study was to investigate whether AIS patients with NIHSS ≤ 5, a limb-related NIHSS item score of 0, and with any of the following NIHSS item ≥2: Best Gaze, Visual, Facial palsy, Limb ataxia, Sensory, Best language, Dysarthria, Extinction and Inattention, could benefit from intravenous thrombolysis.


Eligibility criteria: Inclusion Criteria:

1. Patients with clinical signs of acute ischemic stroke within 4.5 hours of onset or awakening with stroke (if within 4.5 hours from the midpoint of sleep).
2. Patinet's age is \>18 years
3. Patients with NIHSS ≤ 5, a limb-related NIHSS item score of 0, and with any of the following NIHSS item ≥2: Best Gaze, Visual, Facial palsy, Limb ataxia, Sensory, Best language, Dysarthria, Extinction and Inattention.

Exclusion Criteria:

(1) Plan to receive endovascular treatment; (2) Pre-stroke mRS score \> 2 (3) 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; Receiving heparin treatment with aPTT above the upper limit of the normal range within the last 24 hours of onset, Receiving thrombin inhibitors and factor Xa inhibitors within the last 48 hours of onset.
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: 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: the change on the NIHSS score from baseline to 24 hours
timeFrame: 24 hours
measure: Presence of hemorrhagic transformation evaluated by CT or MRI
timeFrame: at day 1
measure: Presence of parenchymal hemorrhage (PH) evaluated by CT or MRI
timeFrame: at day 1
measure: Presence of symptomatic intracerebral hemorrhage (sICH) evaluated by CT or MRI
timeFrame: at day 1
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Second Affiliated Hospital of Zhejiang University, School of Medicine
Study officials:
References: