Remote ischemic conditioning for adults with moderate acute stroke from large artery narrowing

Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke Due to Large Artery Atherosclerosis: A Multi-centered, Open-label, Blind Endpoint, Randomized Controlled Trial

This study will test remote ischemic conditioning plus usual medical care versus usual care alone in adults 18–85 who have a moderate acute ischemic stroke caused by large artery atherosclerosis within 48 hours of symptom onset.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 1150 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT06775782 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized controlled trial with blinded outcome assessment enrolling 1,150 adults aged 18–85 who present within 48 hours of a moderate acute ischemic stroke due to large artery atherosclerosis. Eligible participants have stroke confirmed on MRI and significant large-vessel stenosis or occlusion, with NIHSS scores of 6–16 (or 4–5 with disabling deficits). Participants are randomized 1:1 to receive remote ischemic conditioning (brief cycles of limb blood-flow restriction using a cuff) plus standard medical management or standard medical management alone. The primary endpoint is excellent functional outcome (modified Rankin Scale 0–1) at 90 days, assessed by independent blinded evaluators.

Who should consider this trial

Good fit: Adults 18–85 with MRI-confirmed acute ischemic stroke due to 50%–99% large-artery stenosis or occlusion, presenting within 48 hours and meeting the trial's NIHSS criteria, are ideal candidates.

Not a fit: Patients with strokes from other causes (for example cardioembolism or small-vessel disease), those presenting after 48 hours, with very mild or very severe deficits outside the NIHSS window, or with contraindications to limb cuffing are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, adding remote ischemic conditioning could increase the proportion of patients who recover with little or no disability at 90 days after a moderate stroke from large artery atherosclerosis.

How similar studies have performed: Smaller pilot trials and studies in ischemic conditions have suggested RIC may be beneficial, but large randomized evidence in acute stroke remains limited and results have been mixed.

Eligibility criteria

Inclusion Criteria

1. Male or female with age from 18 to 85 years old;
2. Randomization must be within 48 hours after stroke symptom onset;
3. Ischemic stroke confirmed by MRI diffusion-weighted imaging;
4. NIHSS score 6-16, or 4-5 with disabling deficits at the time of randomization. The following typically should be considered disabling deficits: Complete hemianopsia (≥2 on NIHSS question 3) or severe aphasia (≥2 on NIHSS question 9), or visual or sensory extinction (≥1 on NIHSS question 11) or any weakness limiting sustained effort against gravity (≥2 on NIHSS question 6 or 7);
5. Proven large vessel 50%-99% stenosis or occlusion by MRA, CTA or DSA in cervical or intracranial carotid artery, M1 or M2 segments of the middle cerebral artery, A1 segment of anterior cerebral artery, P1 segment of posterior cerebral artery, vertebral artery, or basilar artery. For patients with single cerebral infarction, when MRA indicates \>50% stenosis rather than occlusion, CTA or DSA should be performed to exclude the risk of MRA overestimating stenosis severity. Acute neurological deficit and cerebral infarction are compatible with ischemia in the vascular territory;
6. Pre-stroke modified Rankin Scale score (mRS) of 0-1;
7. Signed Informed Consent obtained.

Exclusion Criteria

1. Thrombolysis or endovascular therapy performed or planned for index event;
2. Suspected or confirmed cardioembolic source of stroke: i. The aetiology of cardiogenic embolism with high embolic potential, such as atrial fibrillation, atrial flutter, rheumatic mitral or aortic stenosis, artificial heart valve, left atrial myxoma, valve neoplasm, left ventricular wall thrombus, congestive heart failure, bacterial endocarditis, cardiomyopathy, myocardial infarction within previous 30 days; ii. Multiple cerebral infarctions in more than one vascular territory (e.g., bilateral MCA, or an MCA and a basilar artery) confirmed MRI diffusion-weighted imaging;
3. Suspected or confirmed uncommon causes of cerebrovascular disorders: arterial dissection, Moyamoya disease, vasculitis disease, neurosyphilis, radiation induced vasculopathy, fibromuscular dysplasia, benign angiopathy of central nervous system, post-partum angiopathy, suspected vasospastic process, suspected recanalized embolus etc.;
4. Subclavian artery stenosis ≥ 50% or subclavian steal syndrome;
5. Refractory hypertension (defined as persistent systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg after drug treatment);
6. Evidence of intracranial tumor (except small meningioma), abscess, arteriovenous malformation;
7. Patients with bleeding propensity: platelet count \<50×10\^9/L; heparin was administered within 48 hours with APTT≥35s; on anticoagulant therapy with warfarin and International Normalized Ratio (INR) \> 1.7;
8. Undergoing hemodialysis or peritoneal dialysis, or known severe renal insufficiency with glomerular filtration rate \<30 ml/min or serum creatinine \>220 mmol/L (2.5mg/dl);
9. Respiratory failure, including type I and type II;
10. Any contraindication for Remote Ischemic Conditioning: severe soft tissue injury, fracture, peripheral vascular disease, arteriovenous fistula, or venous thrombosis in the upper limbs;
11. Severe comorbid condition with life expectancy \< 6 months；
12. Current participation in any other investigational trial；
13. Pregnancy；
14. Patients not suitable for this clinical study considered by researchers.

Where this trial is running

Xi'an, Shaanxi

• The First Affiliated Hospital of Xi'an Jiaotong University — Xi'an, Shaanxi, China (Recruiting)

Study contacts

• Study coordinator: Suhang Shang

Conditions Acute Ischemic Stroke; Acute Ischemic Stroke；Large Artery Atherosclerosis；Remote Ischemic Conditioning therapy; Randomized Controlled Trial