Clinical trial NCT02534545: Remote Ischemic Conditioning for Avoiding Recurrence of Symptomatic Intracranial Atherosclerotic Stenosis (sICAS)
Official title: Remote Ischemic Conditioning for Avoiding Recurrence of Ischemic Stroke in Patients With Symptomatic Intracranial Atherosclerotic Stenosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Intracranial Atherosclerosis
Keywords: Intracranial atherosclerotic stenosis
ischemia
remote ischemic conditioning
stroke
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2015-08-27
Enrollment: 3000
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The time from randomization to the first occurrence of fatal or non-fatal ischemic stroke.
timeFrame: During the first 12 months from randomization.
Secondary outcomes:
measure: 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) .
timeFrame: During the first 12 months from randomization.
measure: 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.
timeFrame: During the first 12 months from randomization.
measure: Time to death from all causes from randomization.
timeFrame: During the first 12 months from randomization.
Other outcomes:
measure: Scores assessed by National Institutes of Health Stroke Scale(NIHSS)
timeFrame: During the first 12 months from randomization.
measure: Scores assessed by modified Rankin Scale(mRS)
timeFrame: During the first 12 months from randomization.
measure: Scores assessed by Barthel Index(BI).
timeFrame: During the first 12 months from randomization.
measure: Number of participants with abnormal laboratory values
timeFrame: 3 years
measure: Number of participants with adverse events that are related to treatment
timeFrame: 3 years
Locations:
city: Wuhu
country: China
facility: Wuhu NO.2 People's Hospital
state: Anhui
city: Beijing
country: China
facility: The Hospital of Shunyi District Beijing
state: Beijing
city: Beijing
country: China
facility: Beijing Huairou Hospital
state: Beijing
city: Baoding
country: China
facility: Baoding No.1 Hospital
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou People Hospital
state: Hebei
city: Cangzhou
country: China
facility: Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine
state: Hebei
city: Chengde
country: China
facility: Chengde Central Hospital
state: Hebei
city: Handan
country: China
facility: Handan First Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang The First Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang The Third Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Xingtai
country: China
facility: The Third Houspital of Xingtai
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Harbin
country: China
facility: The First Clinical Hospital affiliated to Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The Fourth Hospital of Harbin Medical University
state: Heilongjiang
city: Luohe
country: China
facility: Luohe Central Hospital
state: Henan
city: Shangqiu
country: China
facility: Shangqiu First People's Hospital
state: Henan
city: Xuchang
country: China
facility: Xuchang Central Hospital
state: Henan
city: Zhumadian
country: China
facility: Zhumadian Ctentral Hospital
state: Henan
city: Wuhan
country: China
facility: Technology The Central Hospital of Wuhan
state: Hubei
city: Hohhot
country: China
facility: Inner Mongolia People's Hospital
state: Inner Mongolia
city: Changzhou
country: China
facility: Changzhou NO.2 People's Hospital
state: Jiangsu
city: Anshan
country: China
facility: Anshanshi Changda The Hospital
state: Liaoning
city: Chaoyang
country: China
facility: Chaoyang Central Hospital
state: Liaoning
city: Dalian
country: China
facility: Dalian Municipal Central Hospital Affiliated of Dalian Medical University
state: Liaoning
city: Jinzhou
country: China
facility: Jinzhou Central Hopital
state: Liaoning
city: Jinzhou
country: China
facility: The Third Affiliated Hospital of Liaoning Medical College
state: Liaoning
city: Shenyang
country: China
facility: The First People's Hospital of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military
state: Liaoning
city: Shenyang
country: China
facility: The Peoele's Hospital of Liaoning Province
state: Liaoning
city: Ankang
country: China
facility: Ankang City Central Hospital
state: Shaanxi
city: Dezhou
country: China
facility: Dezhou People's Hospital
state: Shandong
city: Dongying
country: China
facility: Shengli Oilfield Central Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Rizhao
country: China
facility: Rizhao Hospital of Traditional Chinese Medicine
state: Shandong
city: Weifang
country: China
facility: Affiliated Hospital of Weifang Medical University
state: Shandong
city: Changzhi
country: China
facility: Peace Hospital Affiliated to Changzhi Medical College Shanxi Province
state: Shanxi
city: Fenyang
country: China
facility: Fenyang Hospital of Shanxi Medical Unversity
state: Shanxi
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical Unversity
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi College of Traditional Chinese Medicine Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin 4th Centre Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Shaoxing
country: China
facility: Shaoxing Central Hospital
state: Zhejiang
city: Zhoushan
country: China
facility: Zhoushan Putuo Hospital
state: Zhejiang
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Aerospace General Hospital
city: Beijing
country: China
facility: Beijing Luhe Hospital, Capital Medical University
city: Beijing
country: China
facility: Xiyuan Hospital, China Academy of Chinses Medical Sciences
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Xunming Ji, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.