Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke Due to Large Artery Atherosclerosis (RIC-LAA)

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

Large Artery Atherosclerosis is one of the most prevalent causes of stroke worldwide and is associated with a high risk of disability and recurrent strokes. Remote Ischemic Conditioning (RIC) is a promising therapy, and it has been recommended for further investigation in patients with acute ischemic stroke resulting from large artery atherosclerosis. The primary objective of this study is to assess the efficacy of RIC in patients suffering from acute moderate ischemic stroke due to large artery atherosclerosis.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Device: Remote Ischemic Conditioning (RIC) treatment; Drug: Medical Management

Detailed Description

This multi-centered, open-label, blind endpoint, randomized controlled trial aims to investigate the efficacy of RIC in patients with acute moderate ischemic stroke due to large artery atherosclerosis. A total of 1150 participants (age 18 to 85 years) within 48 hours of symptom onset of acute moderate ischemic stroke (NIHSS score 6-16, or NIHSS score 4-5 with disabling deficits) due to large artery atherosclerosis will be enrolled. Eligible patients will be randomized in a 1:1 ratio into RIC treatment plus medical management versus medical management alone after offering informed consent.

The primary endpoint is excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1, which will be evaluated by independent researchers in the blind state.

• Study Type: Interventional
• Enrollment (Estimated): 1150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Suhang Shang; Phone Number: +8618092485760; Email: shangsuhang@mail.xjtu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remote Ischemic Conditioning + Medical Management; Patients in this group will receive Remote Ischemic Conditioning plus best medical management.	Device: Remote Ischemic Conditioning (RIC) treatment; RIC will be given twice a day for 10-14 days. RIC will be applied using an automated RIC device. The cuff of the RIC medical device will be placed around the bilateral upper limbs. Five cycles of cuff inflation (200mmHg for 5 minutes) and deflation (for 5 minutes) for a total procedure time of 50 minutes.; Drug: Medical Management; Patients will receive standard guideline-directed medical therapy, which will include monitor vital signs, management of blood pressure, glucose and lipids, antithrombotic therapy if appropriate.
Active Comparator: Medical Management; Patients in this group will receive best medical management alone.	Drug: Medical Management; Patients will receive standard guideline-directed medical therapy, which will include monitor vital signs, management of blood pressure, glucose and lipids, antithrombotic therapy if appropriate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) 0-1 at 90 days	The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of patients who have suffered from a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. Score 0: No symptoms. Score 1: No significant disability. Able to carry out all usual activities, despite some symptoms. Score 2: Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Score 3: Moderate disability. Requires some help, but able to walk unassisted. Score 4: Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Score 5: Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Score 6: Dead.	at 90 days after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
Modified Rankin Scale (mRS) 0-2 at 90 days	at 90 days after randomization
Distribution of the Modified Rankin Scale (mRS) at 90 days	at 90 days after randomization
Early neurological deterioration within 48 hours	within 48 hours after randomization
Change of NIHSS scores from baseline to 12 days	at 12 days after randomization
Recurrence of Ischemic stroke within 90 days	within 90 days after randomization
Quality of life measured by Euro-QoL-5D-5L at 90 days	at 90 days after randomization
Death due to any cause within 90 days	within 90 days after randomization

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): January 15, 2025

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke；Large Artery Atherosclerosis；Remote Ischemic Conditioning therapy; Randomized Controlled Trial
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia; Atherosclerosis
• Other Study ID Numbers: XJTU1AF-CRF-2023-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No