Antithrombotic Therapy With Regulation of Blood Pressure in Non-Cardioembolic Progressive Stroke

Not Applicable

• Conditions: Stroke, Ischemic
• Interventions: Other: Control group; Other: Intervention group

• Registration Number: NCT06551727
• Lead Sponsor: Ruijin Hospital

Brief Summary

Stroke has become the leading cause of death in China, with acute ischemic stroke still progressing within one week of onset, known as progressive ischemic stroke (PIS), which has a high rate of disability and mortality, accounting for 23-43% of the incidence of stroke. Non-cardioembolic PIS is one of the common types, and the current treatment mainly focuses on antithrombotic therapy, but the therapeutic effect is not satisfactory. More and more evidence suggests that hypotension is an unfavorable factor for PIS, so this study intends to explore the efficacy and safety of antithrombotic therapy with regulation of blood pressure in non-cardioembolic PIS.

Detailed Description

This is a single-center randomized controlled study conducted to explore the efficacy and safety of antithrombotic therapy with regulation of blood pressure in non-cardioembolic PIS.

We plan to recruit 70 patients with non-cardioembolic PIS. All subjects are of Han ethnicity, aged 18 years or older. Gender and age will be statistical data after enrollment. Patients will participate in the study after informed consent.

Then patients who meet the inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to the control group (antithrombotic therapy) or the intervention group (antithrombotic + blood pressure control therapy). In addition to antithrombotic therapy, the intervention group will use medications such as dopamine, metaraminol, or midodrine to control systolic blood pressure within the range of 160-180 mmHg and maintain it for one week.

Patients will be followed up at 2 weeks for mRS (Modified Rankin Scale) and NIHSS (National Institutes of Health Stroke Scale) scores，and at one month for mRS scores, and at three months for mRS and BI (Barthel Index) scores.

Study Timeline

• Study First Submitted: 2024-08-06
• Study First Submitted QC: 2024-08-08
• Study First Posted: 2024-08-13
• Study Start: 2024-08-15
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-11
• Last Update Posted: 2024-10-16
• Primary Completion: 2025-07-15
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Adults (aged ≥18 years) with an AIS who have been able to complete usual activities in daily life without support before the stroke;

2. One of the following PIS manifestations:

   1. Within 7 days of onset, when symptom worsens and there are new lesions or infarct growth on DWI within 24 hours of aggravation, the National Institutes of Health Stroke Scale (NIHSS) score increases by ≥ 2 points ;
   2. Within 24 hours after IVT, when symptom worsens and there are new lesions or infarct growth on DWI within 24 hours of aggravation, the NIHSS score increases by ≥ 4 points compared to the baseline;

3. Within 3h of stroke progression, ≥2 successive measurements of systolic blood pressure (SBP) < 160 mm Hg for >10 min.

4. Computed tomographic angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA) confirms patients without visible large or medium-sized intracranial vessel occlusion.

Exclusion Criteria

1. After stroke progression, a head CT confirmed new cerebral hemorrhage or hemorrhagic transformation.
2. Endovascualr treatment had been performed before stroke progression (thrombectomy, stent placement, balloon dilatation) or if surgery or interventional treatment had been scheduled;
3. Current treatment with heparin therapy or oral anticoagulation (presumed cardiac source of embolus, such as atrial fibrillation, prosthetic cardiac valve, and known or suspected endocarditis);
4. Previous diseases of the brain that include intracranial hemorrhage or amyloid angiopathy; brain surgery or hemorrhagic stroke; stroke within the last three months;
5. Preexisting serious diseases: Cancer, AIDS, serious heart disease, dementia, liver diseases such as liver failure, cirrhosis, portal hypertension and active hepatitis, acute or chronic severe renal impairment (glomerular filtration rate < 30 ml/min/1·73 m2 );
6. Contraindication to aspirin or clopidogrel;
7. Pregnant and lactating women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Control group	After stroke progression, all patients receive dual antiplatelet therapy (aspirin 100mg/day combined with clopidogrel 75mg/day) for the first 21 days, except in cases of cerebral hemorrhage. After this period, they continue to take aspirin 100mg/day orally for the long term.
Intervention group	Intervention group	After stroke progression, all patients receive dual antiplatelet therapy (aspirin 100mg/day combined with clopidogrel 75mg/day) for the first 21 days, except in cases of cerebral hemorrhage. After this period, they continue to take aspirin 100mg/day orally for the long term. In terms of blood pressure control, medications such as dopamine, metaraminol, or midodrine are used to achieve a systolic blood pressure target range of 160-180 mmHg within 1 h of random assignment and to maintain this target for 7 days (or death, should this events occur earlier). Blood pressure measurements were frequently recorded on automated devices applied to the nonhemiparetic arm according to standard guideline recommended procedures, with measurements taken every 15 min in the first hour, hourly between 1 and 6 h, every 6 h between 6 and 24 h, and then twice daily for 7 days (or death, if earlier), and uploaded to the research database.

Primary Outcome Measures

Name	Time	Method
percentage of patients with an excellent outcome（mRS score 0-1）at 90 days after randomization	at 90 days after randomization	modified Rankin scale (mRS，an ordinal global disability scale with scores ranging from 0 \[no symptoms\] to 6 \[death\]) at 90 days after randomization. An excellent outcome is defined as score of 0 or 1 on the mRS score at 90 days.

Secondary Outcome Measures

Name	Time	Method
proportion of patients with outcome measured by NIHSS	at 2 weeks after randomization	outcome measured by NIHSS (0-1 for the NIHSS)
proportion of patients with outcome measured by the Barthel index (BI)	at 90 days after randomization	outcome measured by the Barthel index (BI)，≥ 95 for the BI
proportion of patients with functional independence	at 2 weeks after randomization and at day 30 after randomization	proportion of patients with functional independence (0-2 for the mRS)
proportion of patients with outcome measured by mRS	at 90 days after randomization	outcome measured by mRS，0-2 for mRS
proportion of patients with an excellent outcome	at 2 weeks after randomization and at day 30 after randomization	proportion of patients with an excellent outcome（0-1 for the mRS）
proportion of patients with adverse events	at 90 days after randomization	adverse events，such as allergic reaction，symptoms of hypertensive encephalopathy，etc.
proportion of patients with any bleeding	at 90 days after randomization	any bleeding，such as nasal bleeding, gingival bleeding, skin ecchymosis, etc.
proportion of patients with death	at 90 days after randomization	all cause of death
proportion of patients with severe or moderate bleeding	at 90 days after randomization	severe or moderate bleeding，as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) criteria
proportion of patients with severe adverse events	at 90 days after randomization	severe adverse events, as defined by serious drug side effects and serious unexpected events during the study.

Trial Locations

Locations (1)

Ruijin North Hospital of Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China