ALteplase in Patients With LOW NIHSS and Specified Disabling Deficits (ALLOW)

Zhejiang University

Status and phase: Enrolling; Phase 4

Conditions: Thrombosis

Treatments: Drug: Alteplase

Study type: Interventional

Funder types: Other

Identifiers

NCT06115070

ALLOW

Details and patient eligibility

About

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. Therefore, the center developed a mild stroke EMSS assessment scale to refine the disability assessment of stroke symptoms. It was found that intravenous thrombolytic therapy was safe and effective for patients with symptoms such as dizziness, disorientation, memory impairment, decreased muscle strength at the proximal end of one limb, and ataxia while standing.

Therefore, the purpose of this study was to investigate whether ischemic stroke patients with onset or detection time within 4.5 hours, and mild stroke patients with NIHSS score ≤5 with any of the following symptoms: dizziness, disorientation, memory impairment, single proximal muscle strength decline, or ataxia while standing could benefit from intravenous thrombolysis based on CT/MRI screening in the Chinese population.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age of onset ≥18 years;
2. Patients with acute cerebral infarction or transient ischemic attack within 4.5 hours of onset;
3. NIHSS≤5, and EMSS score ≥2 combined with any of the following conditions A. Dizziness B. Whole brain - orientation D. Speech E. Upper/lower limb muscle strength F. Ataxia - Standing

Exclusion criteria

1. pre-disease mRS≥2;
2. Obvious history of head trauma or stroke in the past 3 months;
3. Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extrinsic hematoma);
4. Previous history of intracranial hemorrhage;
5. Intracranial tumors and giant intracranial aneurysms;
6. Had intracranial or intraspinal surgery in the past 3 months;
7. Arterial puncture in the incompressible area within the last 1 week;
8. Gastrointestinal or urinary tract bleeding within the past 21 days;
9. Major surgical operations within the last 2 weeks;
10. Uncontrolled severe hypertension (systolic blood pressure ≥180mmHg or diastolic blood pressure ≥100mmHg after medication);
11. Blood sugar <2.8mmol/L or > 22.22mmol/L;
12. Have received heparin therapy or oral anticoagulant therapy within 48 hours;
13. Platelet count <100,000/mm3 (if clinical abnormality is not suspected, validation before randomization is not required);
14. Taking oral warfarin with INR>1.6;
15. PT > 15s;
16. Pregnancy;
17. Allergic to the experimental drug;
18. Diagnosed Alzheimer's disease, frontotemporal dementia, schizophrenia
19. Patients deemed unsuitable for participation in this trial by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

300 participants in 2 patient groups

Thrombolysis group

Experimental group

Description:

intravenous alteplase (0.9 mg/kg; maximum dose, 90mg; 10% administered as a 1-minute bolus, the remaining infused over 1 hour;

Treatment:

Drug: Alteplase

Control group

No Intervention group

Description:

according to guideline