Intravenous Thrombolytic Therapy for Acute Ischemic Stroke Patients with Low NIHSS and Non-disabling Deficits

NCT06115070 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: ALLOW
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 1

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.

Conditions

Thrombosis; Acute Ischemic Stroke (AIS)

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)

• 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

• the change on the NIHSS score from baseline to 24 hours

  24 hours

• Presence of hemorrhagic transformation evaluated by CT or MRI

  at day 1

Study Arms (2)

Intravenous thrombolysis (alteplase and other guideline-recommended thrombolytic agents)

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 (alteplase and other guideline-recommended thrombolytic agents)

Standard therapy

NO INTERVENTION

Standard therapy

Interventions

Intravenous thrombolysis (alteplase and other guideline-recommended thrombolytic agents) 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 (alteplase and other guideline-recommended thrombolytic agents)

Eligibility Criteria

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

You may qualify if:

• 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).
• Patinet's age is \>18 years
• 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.

You may not qualify if:

• (1) Plan to receive endovascular treatment; (2) Pre-stroke mRS score \> 2 (3) Contraindications for IVT：
• Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hematoma, etc.)
• Previous history of intracranial hemorrhage
• Severe head trauma or stroke history within the last 3 months
• Intracranial tumors, giant intracranial aneurysms
• Intracranial or spinal surgery within the recent 3 months
• Major surgical procedures within the last 2 weeks
• Gastrointestinal or urinary tract bleeding within the last 3 weeks
• Active visceral bleeding
• Aortic arch dissection
• Arterial puncture in a site within the last 1 week that is not easy to compress and stop bleeding
• Elevated blood pressure: Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg
• Acute bleeding tendency, including platelet count \< 100 × 10⁹/L or other conditions
• Received low-molecular-weight heparin treatment within 24 hours
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, China

Location

MeSH Terms

Conditions

Thrombosis; Ischemic Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2023
• First Posted: November 2, 2023
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)