Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS)

Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS): a Prospective, Random, Open Label, Blinded End Point, Multi-center Study

The current treatment based on evidence-based medicine for acute ischemic stroke mainly includes reperfusion (intravenous thrombolysis, mechanical thrombolysis), anti-platelet and stroke units. About 1/3 patients can obtain good prognosis through intravenous thrombolysis. Good prognosis can be gotten from about 50 percent of patients with big artery disease by mechanical embolization. However, only a small proportion of the population can be treated with restoration perfusion in the time window. The main purpose of antiplatelet therapy is to prevent the recurrence and progression of stroke, and stroke unit is a kind of management mode. How to improve the neurological function of patients has been a hot and difficult problem in clinical practice.

A large number of basic and clinical studies have proved that remote ischemic conditioning (RIC) has protective effect on ischemic stroke. Hahn et al showed that RIC could play a neuroprotective role in cerebral ischemia-reperfusion injury in MCAO model. Other studies have also confirmed that preconditioning RIC has a neuroprotective effect on cerebral ischemia in animal models. One open label study by Hougaard et al shows that RIC can improve the NIHSS score in acute ischemic stroke patients. One recent study found that 300 consecutive days RIC therapy for the patients with symptomatic intracranial atherosclerotic stenosis significantly reduced the recurrence rate of stroke, improved the mRS score and recovered the blood flow in the lesion site. Furthermore, several studies have also shown that RIC can not only improve the neurological function of patients with cerebral infarction after intravenous thrombolysis and mechanical thrombolysis, but also protect the secondary brain injury after carotid stenting. These results suggest that RIC has a neuroprotective effect on ischemic stroke and deserves further study.

Based on the above discussion, this study aims to explore the efficacy and safety of RIC in the treatment of acute moderate ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Remote Ischemic Conditioning treatment; Drug: Guideline-based therapy

• Study Type: Interventional
• Enrollment (Actual): 1800
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • ShenYang, China
    • General Hospital of Shenyang Military Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient age ≥18 years;
2. From onset to treatment ≤ 48 hours;
3. Ischemic stroke confirmed by head CT or MRI;
4. 6≤NIHSS score ≤ 16;
5. Premorbid mRS ≤ 1;
6. Signed informed consent.

Exclusion Criteria:

1. Serious neurological deficits before onset ( mRS ≥ 2)；
2. The aetiology of cardiogenic embolism, such as rheumatic mitral or aortic stenosis, artificial heart valve, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, left ventricular wall thrombus or valve neoplasm, congestive heart failure, bacterial endocarditis, etc;
3. Uncontrolled severe hypertension (Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg after drug treatment);
4. Subclavian artery stenosis ≥ 50% or subclavian steal syndrome;
5. Intracranial tumor, arteriovenous malformation or aneurysm;
6. Severe abnormalities in coagulation;
7. Any contraindication for remote ischemic adaptation: the upper limb has serious soft tissue injury, fracture or vascular injury, distal upper limb perivascular lesions, etc.;
8. Comorbidity with any serious diseases and life expectancy is less than half a year;
9. Participating in other clinical trials within 3 months;
10. Patients not suitable for this clinical studies considered by researcher;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Guideline-based therapy+RIC; RIC is given twice a day with 200mmHg pressure.	Device: Remote Ischemic Conditioning treatment; Remote Ischemic Conditioning is given twice a day with 200mmHg pressure.
Active Comparator: Guideline-based therapy	Drug: Guideline-based therapy; Guideline-based therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of mRS (0-1）	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of mRS (0-2）		90±7 days
Incidence of early neurological deterioration	more than 4 NIHSS score increase compared with baseline	7 days
Incidence of stroke associated pneumonia		12±2 days
occurrence of stroke or other vascular events		90±7 days
proportion of death of any cause		90±7 days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Publications and helpful links

General Publications

• Chen HS, Cui Y, Li XQ, Wang XH, Ma YT, Zhao Y, Han J, Deng CQ, Hong M, Bao Y, Zhao LH, Yan TG, Zou RL, Wang H, Li Z, Wan LS, Zhang L, Wang LQ, Guo LY, Li MN, Wang DQ, Zhang Q, Chang DW, Zhang HL, Sun J, Meng C, Zhang ZH, Shen LY, Ma L, Wang GC, Li RH, Zhang L, Bi C, Wang LY, Wang DL; RICAMIS Investigators. Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial. JAMA. 2022 Aug 16;328(7):627-636. doi: 10.1001/jama.2022.13123.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2018
• Primary Completion (Actual): April 19, 2021
• Study Completion (Actual): April 19, 2021

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: k（2018）43

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No