ALteplase in Patients With LOW NIHSS and Specified Disabling Deficits

Thrombosis Clinical Trial

— ALLOW  

Official title:

ALteplase for the Treatment of Acute Ischemic Stroke in Patients With LOW National Institutes of Health Stroke Scale and Specified Disabling Deficits

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06115070
• Other study ID #: ALLOW
• Status: Recruiting
• Phase: Phase 4
• Start date: November 17, 2023
• Est. completion date: November 30, 2026

Study information

• Verified date: October 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Thrombosis

Intervention

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

Locations

Country	Name	City	State
China	Second Affiliated Hospital of Zhejiang University, School of Medicine	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Symptomatic bleeding transformation within 24 hours	ECASSIII definition	within 24 hours
Other	Life-threatening systemic bleeding within 7 days	Bleeding Academic Research Consortium(BARC) 4, 3a, 3b, and 3c within 7 days	within 7 days
Primary	excellent functional outcome at 90 days, defined as a score of 0 to 1 on the mRS for the evaluation of neurologic disability	defined as a score of 0 to 1 on the mRS for the evaluation of neurologic disability	90 days
Secondary	The percentage of mRS Score 0-2	defined as a score of 0 to 2 on the mRS for the evaluation of neurologic disability	90 days
Secondary	Early neurological function improved at 7 days, and NIHSS score decreased by =2 points compared with baseline	defined as NIHSS score decreased by =2 points compared with baseline	7 days
Secondary	Early neurological deterioration caused by non-intracranial hemorrhage at 7 days: NIHSS score increased by =2 points	defined as NIHSS score increased by =2 points compared with baseline	7 days
Secondary	Cognitive function assessment	Hopkins Verbal Learning Test-Revised [HVLT-R] trials 1, 2, and 3; digit symbol coding from the Wechsler Adult Intelligence Scale III [WAIS III]; Forward and Backward Digit Span test; Benton Judgment of Line Orientation test, form V; HVLT-R trial 4 and recognition; semantic fluency [Animal Naming test]; Boston Naming Test [BNT; 15-item short form]) at 6-month	6 months
Secondary	Cognitive function assessment	Hopkins Verbal Learning Test-Revised [HVLT-R] trials 1, 2, and 3; digit symbol coding from the Wechsler Adult Intelligence Scale III [WAIS III]; Forward and Backward Digit Span test; Benton Judgment of Line Orientation test, form V; HVLT-R trial 4 and recognition; semantic fluency [Animal Naming test]; Boston Naming Test [BNT; 15-item short form]) at 1-year	1 year
Secondary	Changes in functional brain connectivity	Changes in functional brain connectivity by function MRI	6 months
Secondary	Barthel Index	Barthel Index	3 months