Remote Ischemic Conditioning for Avoiding Recurrence of Symptomatic Intracranial Atherosclerotic Stenosis (sICAS)

Remote Ischemic Conditioning for Avoiding Recurrence of Ischemic Stroke in Patients With Symptomatic Intracranial Atherosclerotic Stenosis

The primary objective of the study will be to determine whether remote limb ischemic conditioning (RLIC) compared with sham RLIC (placebo) treatment reduces the 12-month risk of recurrent IS in patients with a recent TIA or IS caused by stenosis of a major intracranial artery.

After screening period, eligible patients will be randomly allocated into 2 groups. In addition, all participants receive an usual clinical therapy.

Study Overview

• Status: Unknown
• Conditions: Intracranial Atherosclerosis
• Intervention / Treatment: Device: Doctormate® (200mmHg); Device: Doctormate® (60mmHg)

Detailed Description

In this study, Patients in the RLIC group will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (200mmHg) once daily for 12 months; patients in the sham RLIC group will be treated with the Renqiao Remote Ischemic Conditioning Device (Doctormate®) (60mmHg) once daily for 12 months. In the study, the RLIC treatment will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. Sham RLIC treatment will be conducted using the same procedure but with a minimal inflation pressure of 60mmHg, which does not result in upper limb ischemia. In addition, all participants will have received their usual drug therapy according to local medical practice.

• Study Type: Interventional
• Enrollment (Anticipated): 3000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100053
    • Recruiting
    • Xuanwu Hospital, Capital Medical University
  • Beijing, China
    • Recruiting
    • Beijing aerospace general hospital
    • Contact: Jilai Li
    • Principal Investigator: Jilai Li
  • Beijing, China
    • Recruiting
    • Beijing Luhe Hospital, Capital Medical University
    • Contact: Huishan Du
    • Principal Investigator: Huishan Du
  • Beijing, China
    • Recruiting
    • Xiyuan Hospital, China Academy of Chinses Medical Sciences
    • Contact: Chenguang Tong
    • Principal Investigator: Chenguang Tong
  • Anhui
    • Wuhu, Anhui, China
      • Recruiting
      • Wuhu NO.2 People's Hospital
      • Contact: Hongbo Pang
      • Principal Investigator: Hongbo Pang
  • Beijing
    • Beijing, Beijing, China, 101300
      • Recruiting
      • The Hospital of Shunyi District Beijing
      • Contact: Quping Ouyang
      • Principal Investigator: Quping Ouyang
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Huairou Hospital
      • Contact: Fuying Yu
      • Principal Investigator: Fuying Yu
  • Hebei
    • Baoding, Hebei, China
      • Recruiting
      • Baoding No.1 Hospital
      • Contact: Chunsheng Wang
      • Principal Investigator: Chunsheng Wang
    • Cangzhou, Hebei, China
      • Recruiting
      • Cangzhou People Hospital
      • Contact: Jie Huang
      • Principal Investigator: Jie Huang
    • Cangzhou, Hebei, China
      • Recruiting
      • Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine
      • Contact: Zhiyong Wang
      • Principal Investigator: Zhiyong Wang
    • Chengde, Hebei, China
      • Recruiting
      • Chengde Central Hospital
      • Contact: Haisong Du
      • Principal Investigator: Haisong Du
    • Handan, Hebei, China
      • Recruiting
      • Handan First Hospital
      • Contact: Liping Cheng
      • Principal Investigator: Liping Cheng
    • Shijiazhuang, Hebei, China
      • Recruiting
      • Hebei General Hospital
      • Contact: Peiyuan Lu
      • Principal Investigator: Peiyuan Lu
    • Shijiazhuang, Hebei, China
      • Recruiting
      • The Second Hospital of Hebei Medical University
      • Contact: Xueqin Song
      • Principal Investigator: Xueqin Song
    • Shijiazhuang, Hebei, China
      • Recruiting
      • Shijiazhuang The First Hospital
      • Contact: Zhenquan Yan
      • Principal Investigator: Zhenquan Yan
    • Shijiazhuang, Hebei, China
      • Recruiting
      • Shijiazhuang The Third Hospital
      • Contact: Yunshu Zhang
      • Principal Investigator: Yunshu Zhang
    • Xingtai, Hebei, China
      • Recruiting
      • Xingtai People's Hospital
      • Contact: Peilin Hu
      • Principal Investigator: Peilin Hu
    • Xingtai, Hebei, China
      • Recruiting
      • The Third Houspital of Xingtai
      • Contact: Yuqing Wei
      • Principal Investigator: Yuqing Wei
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Recruiting
      • The Fourth Hospital of Harbin Medical University
      • Contact: Zhuobo Zhang
    • Harbin, Heilongjiang, China
      • Recruiting
      • The First Clinical Hospital affiliated to Harbin Medical University
      • Contact: Guozhong Li
      • Principal Investigator: Guozhong Li
  • Henan
    • Luohe, Henan, China
      • Recruiting
      • Luohe Central Hospital
      • Contact: Chunling Zheng
      • Principal Investigator: Chunling Zheng
    • Shangqiu, Henan, China
      • Recruiting
      • Shangqiu First People's Hospital
      • Contact: Yan Fang
      • Principal Investigator: Yan Fang
    • Xuchang, Henan, China
      • Recruiting
      • Xuchang Central Hospital
      • Contact: Tao Li
      • Principal Investigator: Tao Li
    • Zhumadian, Henan, China
      • Recruiting
      • Zhumadian Ctentral Hospital
      • Contact: Xuezhang Lai
      • Principal Investigator: Xuezhang Lai
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Technology The Central Hospital of Wuhan
      • Contact: Linhong Zhang
      • Principal Investigator: Linhong Zhang
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China
      • Recruiting
      • Inner Mongolia People's Hospital
      • Contact: Runxiu Zhu
      • Principal Investigator: Runxiu Zhu
  • Jiangsu
    • Changzhou, Jiangsu, China
      • Recruiting
      • Changzhou No.2 People's Hospital
      • Contact: Zhuoyou Chen
      • Principal Investigator: Zhuoyou Chen
  • Liaoning
    • Anshan, Liaoning, China
      • Recruiting
      • Anshanshi Changda The Hospital
      • Contact: Xiujie Han
      • Principal Investigator: Xiujie Han
    • Chaoyang, Liaoning, China
      • Recruiting
      • Chaoyang Central Hospital
      • Contact: Xiaomei He
      • Principal Investigator: Xiaomei He
    • Dalian, Liaoning, China
      • Recruiting
      • Dalian Municipal Central Hospital Affiliated of Dalian Medical University
      • Contact: Hong Wang
    • Jinzhou, Liaoning, China
      • Recruiting
      • Jinzhou Central Hopital
      • Contact: Dongyu Wang
      • Principal Investigator: Dongyu Wang
    • Jinzhou, Liaoning, China
      • Recruiting
      • The Third Affiliated Hospital of Liaoning Medical College
      • Contact: Hui Zhang
      • Principal Investigator: Hui Zhang
    • Shenyang, Liaoning, China
      • Recruiting
      • The First People's Hospital of Shenyang
      • Contact: Jin Zhou
      • Principal Investigator: Jin Zhou
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The General Hospital of Shenyang Military
      • Contact: Huisheng Chen
      • Principal Investigator: Huisheng Chen
    • Shenyang, Liaoning, China
      • Recruiting
      • The Peoele's Hospital of Liaoning Province
      • Principal Investigator: Xiaohong Chen
      • Contact: Xiaohong Chen
  • Shaanxi
    • Ankang, Shaanxi, China
      • Recruiting
      • Ankang City Central Hospital
      • Contact: Kaifu Jiang
      • Principal Investigator: Kaifu Jiang
  • Shandong
    • Dezhou, Shandong, China
      • Recruiting
      • Dezhou People'S Hospital
      • Contact: Shaohua Su
      • Principal Investigator: Shaohua Su
    • Dongying, Shandong, China
      • Recruiting
      • Shengli Oilfield Central Hospital
      • Contact: Zongen Gao
      • Principal Investigator: Zongen Gao
    • Linyi, Shandong, China
      • Recruiting
      • Linyi People's Hospital
      • Contact: Hongxing Han
      • Principal Investigator: Hongxing Han
    • Rizhao, Shandong, China
      • Recruiting
      • Rizhao Hospital of Traditional Chinese Medicine
      • Contact: Wei Ding
      • Principal Investigator: Wei Ding
    • Weifang, Shandong, China
      • Recruiting
      • Affiliated hospital of Weifang Medical University
      • Contact: Xianwei Zeng
      • Principal Investigator: Xianwei Zeng
  • Shanxi
    • Changzhi, Shanxi, China
      • Recruiting
      • Peace Hospital Affiliated to Changzhi Medical College Shanxi Province
      • Contact: Yufen Wang
      • Principal Investigator: Yufen Wang
    • Fenyang, Shanxi, China
      • Recruiting
      • Fenyang Hospital of Shanxi Medical Unversity
      • Contact: Xueying Guo
      • Principal Investigator: Xueying Guo
    • Taiyuan, Shanxi, China
      • Recruiting
      • First Hospital of Shanxi Medical Unversity
      • Contact: Xiaoyuan Niu
      • Principal Investigator: Xiaoyuan Niu
    • Taiyuan, Shanxi, China
      • Recruiting
      • Shanxi College of Traditional Chinese Medicine Hospital
      • Contact: Aimei Wang
      • Principal Investigator: Aimei Wang
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Medical University General Hospital
      • Contact: Junwei Hao
      • Principal Investigator: Junwei Hao
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Huanhu Hospital
      • Contact: Wei Yue
      • Principal Investigator: Wei Yue
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin 4th Centre Hospital
      • Contact: Hongxin Wang
      • Principal Investigator: Hongxin Wang
  • Zhejiang
    • Shaoxing, Zhejiang, China
      • Recruiting
      • Shaoxing central hospital
      • Contact: Ke Shen
      • Principal Investigator: Ke Shen
    • Zhoushan, Zhejiang, China
      • Recruiting
      • Zhoushan Putuo Hospital
      • Principal Investigator: Ming Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female with age from 40 to 80 years old.

2. Patients having an ischemic stroke or a TIA prior to randomization.

   • Patient having an ischemic stroke within 30 days with mRS score≤4 at baseline.
   • Patient having a TIA within 15 days with Oxfordshire Community Stroke Project on the basis of age, blood pressure (BP), clinical features, and duration of TIA symptoms (ABCD2) score≥4 at baseline.
3. The entry event is attributed to symptomatic atherosclerotic stenosis (50-99%) in an intracranial qualifying artery (carotid artery, middle cerebral artery (M1), vertebral artery, or basilar artery) that is documented by magnetic resonance angiography (MRA) or computed tomographic angiography (CTA).
4. Informed consent obtained.

Exclusion Criteria:

1. Thrombolytic therapy within 24 hours prior to enrollment.
2. Progressive neurological signs within 24 hours prior to enrollment.
3. Cerebral venous thrombosis/stenosis.
4. Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebrospinal fluid (CSF) pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus.
5. Any of the following unequivocal cardiac source of embolism: rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial fibrillation, atrial flutter, sick sinus syndrome, left atrial myxoma, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, bacterial endocarditis, or any other cardiovascular condition interfering with the participation.
6. Uncontrolled severe hypertension [sitting systolic blood pressure (SBP) >180 mmHg and/or sitting diastolic blood pressure (DBP) >110 mmHg after medication].
7. Patients with abnormal laboratory parameters: aspartate transaminase (AST) and/or alanine transaminase (ALT) >3×upper limit of normal range; creatinine clearance <0.6 ml/s and/or serum creatinine >265 μmol/l (>3.0 mg/dl); platelets <100×109/L.
8. Any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural) within 90 days prior to enrollment.
9. Intracranial neoplasm, cerebral aneurysm or arteriovenous malformation.
10. Known retinal hemorrhage or visceral bleeding within 30 days prior to enrollment.
11. Severe hemostatic disorder or severe coagulation dysfunction.
12. Subclavian arterial stenosis≥50% or subclavian steal syndrome.
13. Extracranial stenosis ≥50%.
14. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform one of these procedures within 12 months after enrollment.
15. Major surgery (including open femoral, aortic, or carotid surgery, cardiac) within previous 30 days or scheduled in the 12 months after enrollment.
16. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
17. Life expectancy<3 years.
18. Pregnant or breast-feeding women.
19. Unwilling to be followed up or poor compliance for treatment.
20. Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial.
21. Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doctormate® (200mmHg); Patients will be treated with Renqiao Remote Ischemic Conditioning Device (Doctormate®) (200mmHg) once daily for 12 months	Device: Doctormate® (200mmHg); Limb ischemia was induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®) inflating tourniquets to 200mmHg.
Sham Comparator: Doctormate® (60mmHg); Patients will be treated with the Renqiao Remote Ischemic Conditioning Device (Doctormate®) (60mmHg) once daily for 12 months	Device: Doctormate® (60mmHg); Limb ischemia was induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®) inflating tourniquets to 60mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The time from randomization to the first occurrence of fatal or non-fatal ischemic stroke.	During the first 12 months from randomization.

Secondary Outcome Measures

Outcome Measure	Time Frame
The time from randomization to the first occurrence of a composite of fatal or non-fatal stroke (ischemic and hemorrhagic), fatal or non-fatal myocardial infarction, and transient ischemic attack (TIA) .	During the first 12 months from randomization.
The time from randomization to the first occurrence of each component of the composite of fatal or non-fatal stroke (ischemic and hemorrhagic), fatal or non-fatal myocardial infarction, and TIA.	During the first 12 months from randomization.
Time to death from all causes from randomization.	During the first 12 months from randomization.

Other Outcome Measures

Outcome Measure	Time Frame
Scores assessed by National Institutes of Health Stroke Scale(NIHSS)	During the first 12 months from randomization.
Scores assessed by modified Rankin Scale(mRS)	During the first 12 months from randomization.
Scores assessed by Barthel Index(BI).	During the first 12 months from randomization.
Number of participants with abnormal laboratory values	3 years
Number of participants with adverse events that are related to treatment	3 years

Collaborators and Investigators

• Sponsor: Ji Xunming,MD,PhD

Publications and helpful links

General Publications

• Hou C, Lan J, Lin Y, Song H, Wang Y, Zhao W, Li S, Meng R, Hao J, Ding Y, Chimowitz MI, Fisher M, Hess DC, Liebeskind DS, Hausenloy DJ, Huang J, Li Z, Han X, Yang J, Zhou J, Chen P, Zhu X, Hu P, Pang H, Chen W, Chen H, Li G, Tao D, Yue W, Gao Z, Ji X; RICA investigators. Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China. Lancet Neurol. 2022 Dec;21(12):1089-1098. doi: 10.1016/S1474-4422(22)00335-0. Epub 2022 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: August 23, 2015
• First Submitted That Met QC Criteria: August 26, 2015
• First Posted (Estimate): August 27, 2015

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: May 23, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: stroke; remote ischemic conditioning; ischemia; Intracranial atherosclerotic stenosis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Pathological Conditions, Anatomical; Intracranial Arterial Diseases; Recurrence; Constriction, Pathologic; Atherosclerosis; Intracranial Arteriosclerosis
• Other Study ID Numbers: RICA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided