Clinical trial NCT06559241: Remote Ischemic Conditioning for Acute Ischemic Stroke Treated with Mechanical Thrombectomy（RECAST-MT）
Official title: Safety and Efficacy of Remote Ischemic Conditioning for Acute Ischemic Stroke Treated with Mechanical Thrombectomy (RECAST-MT): a Multicenter, Randomized, Controlled, Open-label, Blinded Endpoint Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Anterior Circulation Brain Infarction
Keywords: Endovascular thrombectomy
Cerebroprotection
Remote ischemic conditioning
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2024-08-19
Enrollment: 2105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: For patients with acute ischemic stroke caused by large vessel occlusion, endovascular thrombectomy has been demonstrated to be the most effective therapy, as approximately 90% of the occluded vessels can be recanalized. However, less than 50% of patients could achieve functional independence, and over 15% died 90 days after stroke. Although the mismatch of successful recanalization with poor prognosis can be attributed to many factors, the infarct core formed during thrombectomy and reperfusion injury after thrombectomy may be among the most important and effective neuroprotective strategies urgently needed.

Remote ischemic conditioning (RIC) is a noninvasive strategy in which one or more cycles of brief and transient limb ischemia confer protection against prolonged and severe ischemia in distant organs. In the transient focal cerebral ischemia-reperfusion model, the application of remote ischemic conditioning before reperfusion or both before and after reperfusion reduces reperfusion injuries and the final infarct size. Because patients with acute ischemic stroke who are treated with endovascular thrombectomy can achieve a high rate of recanalization after focal ischemia, this patient population is akin to the model of transient focal cerebral ischemia-reperfusion. Furthermore, a pilot study has determined the safety and feasibility of remote ischemic conditioning in patients undergoing endovascular thrombectomy. However, whether remote ischemic conditioning could provide clinical benefits to patients with acute ischemic stroke who are treated with endovascular thrombectomy urgently needs investigations.

This study aims to investigate the safety and efficacy of remote ischemic conditioning in improving functional outcomes of patients with acute ischemic stroke treated with endovascular thrombectomy and explore the effect of treatment duration on the treatment outcome of remote ischemic conditioning.


Eligibility criteria: Inclusion Criteria:

1. Age≥18 years；
2. Acute ischemic stroke due to large vessel occlusion in the anterior circulation that is not suitable for intravenous thrombolytic therapy, or has contraindications to intravenous thrombolytic therapy, or treated with intravenous thrombolytic therapy without recanalization;
3. Large vessel occlusion confirmed by computed tomography angiography (CTA) or magnetic resonance angiography (MRA), including the occlusion of the intracranial segment of the internal carotid artery (ICA) and M1 segment of the middle cerebral artery (MCA), is the cause of symptoms, and mechanical thrombectomy is planned within 24 hours from the time last known well;
4. Baseline score of the National Institutes of Health Stroke Scale (NIHSS) ≥ 6 points;
5. Patients or family members signed a written informed consent form.

Exclusion Criteria:

1. Imaging examination revealed the presence of multiple vascular supply areas of cerebral infarction (such as the simultaneous presence of infarction in both anterior and posterior circulation);
2. Absence of femoral artery pulsation, extremely difficult intravascular access, or extremely tortuous large vessels, which are expected to result in the inability to undergo timely endovascular treatment;
3. Difficult-to-control hypertension: continuous monitoring upon admission shows systolic blood pressure ≥180mmHg, or diastolic blood pressure ≥100mmHg;
4. Coma or lethargy patients (consciousness level score ≥2 in NIHSS);
5. Unable to obtain an accurate baseline NIHSS score;
6. Pre-stroke modified Rankin Scale (mRS) score \>1;
7. Baseline ASPECTS score ≤5;
8. Presence of bleeding tendency, deficiency of coagulation factors, or oral anticoagulant therapy with INR \> 3.0;
9. Baseline blood glucose \<2.7mmol/L or \>22.2mmol/L;
10. Baseline platelet count \< 30\*10\^9/L;
11. Severe known renal impairment defined as requiring dialysis (hemodialysis or peritoneal dialysis), or if known creatinine clearance rate \<30mL/min;
12. Cranial CT or MRI shows intracranial hemorrhage;
13. Cranial CT or MRI shows midline deviation and significant occupying effect;
14. Clinical history, previous imaging examinations, or clinical judgment suggesting intracranial tumors, arteriovenous malformations, or intracranial arterial dissection;
15. History of head injury in the past 3 months;
16. History of life-threatening allergy to contrast agents, nickel, titanium metal, or their alloys;
17. Pregnancy, if women of childbearing age have a positive urinary or serum β-human chorionic gonadotropin (β-hCG) test or are breastfeeding；
18. The life expectancy of patients is less than 6 months, and they cannot be evaluated within 3 months;
19. Limb deformity, soft tissue injury, or other conditions that affect the implementation of distant ischemia adaptation therapy;
20. Participating in other ongoing clinical trials;
21. Other conditions that the investigators believe are not suitable for participation in this study.

Primary outcomes:
measure: The proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days.
timeFrame: 90 days after stroke.
Secondary outcomes:
measure: Two dichotomous mRS scores at 90 days (0-1 vs 2-6, 0-3 vs 4-6, 0-4 vs 5-6, 0-5 vs 6).
timeFrame: 90 days after stroke.
measure: The ordinal distribution of mRS scores at 90 days.
timeFrame: 90 days after stroke.
measure: The proportion of patients with early neurological improvement 24 hours after endovascular procedures.
timeFrame: 24 hours after endovascular procedures.
measure: Changes in NIHSS score from baseline to day 14 or at discharge (whichever comes earlier).
timeFrame: 14 days or at discharge (whichever comes first)
measure: Score of EQ-5D-5L at 90 days.
timeFrame: 90 days after stroke.
measure: Cerebral infarct volume.
timeFrame: 72 hours after endovascular procedures.
measure: The change of infarct volume.
timeFrame: 72 hours after endovascular procedures.
measure: Incidence of intracranial hemorrhage.
timeFrame: Within 14 days after endovascular procedures.
measure: Incidence of Symptomatic Intracranial Hemorrhage
timeFrame: Within 14 days after endovascular procedures.
measure: Incidence of neurological deterioration within 14 days.
timeFrame: Within 14 days after endovascular procedures.
measure: Incidence of malignant infarction
timeFrame: 0-90 days
measure: All cause of death.
timeFrame: 0-90 days
measure: Incidence of Adverse Events/Serious Adverse Events
timeFrame: 0-90 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Luhe Hospital affiliated to Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Fangshan District First Hospital
state: Beijing
city: Shenzhen
country: China
facility: Shenzhen qianhai shekou free trade zone hospital
state: Guangdong
city: Shenzhen
country: China
facility: South China Hospital Affiliated to Shenzhen University
state: Guangdong
city: Nanning
country: China
facility: Nanning Second People's Hospital
state: Guangxi
city: Jiamusi
country: China
facility: Jiamusi university hongda hospital
state: Heilongjiang
city: Jiaozuo
country: China
facility: Jiaozuo Coal Industry Group Co., Ltd. Central Hospital
state: Henan
city: Luoyang
country: China
facility: Luoyang Yanshi People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Province People's Hospital
state: Henan
city: Zhoukou
country: China
facility: Xihua county people's hospital
state: Henan
city: Huanggang
country: China
facility: Huanggang Centralhospital
state: Hubei
city: Huangshi
country: China
facility: Huangshi central hospital
state: Hubei
city: Jingmen
country: China
facility: Jingmen No.1 People's Hospital
state: Hubei
city: Jingmen
country: China
facility: Jingmen people's hospital
state: Hubei
city: Tianmen
country: China
facility: First People's Hospital of Tianmen
state: Hubei
city: Wuhan
country: China
facility: Wuhan University Zhongnan Hospital
state: Hubei
city: Xiangyang
country: China
facility: The First People's Hospital of Xiangyang
state: Hubei
city: Yichang
country: China
facility: Yichang Central People's Hospital
state: Hubei
city: Changde
country: China
facility: the First People'S Hospital of Changde
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region People's Hospital
state: Inner Mongolia Autonomous Region
city: Anshan
country: China
facility: Anshan zhangda hospital
state: Liaoning
city: Dalian
country: China
facility: Dalian Central Hospital
state: Liaoning
city: Dongying
country: China
facility: The Central Hospital of Shengli Oilfield
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng Third People's Hospital
state: Shandong
city: Liaocheng
country: China
facility: The People's Hospital of Liaocheng Brain Hospital
state: Shandong
city: Linyi
country: China
facility: Feixian county people's hospital
state: Shandong
city: Mianyang
country: China
facility: Mianyang third people's hospital
state: Sichuan
city: Ya'an
country: China
facility: Ya 'an People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin huanhu hospital
state: Tianjin
city: Wenzhou
country: China
facility: The Second Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
References:
citation: Zhao W, Meng R, Ma C, Hou B, Jiao L, Zhu F, Wu W, Shi J, Duan Y, Zhang R, Zhang J, Sun Y, Zhang H, Ling F, Wang Y, Feng W, Ding Y, Ovbiagele B, Ji X. Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial. Circulation. 2017 Apr 4;135(14):1325-1335. doi: 10.1161/CIRCULATIONAHA.116.024807. Epub 2017 Feb 7.
citation: Zhao W, Wu C, Dornbos D 3rd, Li S, Song H, Wang Y, Ding Y, Ji X. Multiphase adjuvant neuroprotection: A novel paradigm for improving acute ischemic stroke outcomes. Brain Circ. 2020 Feb 18;6(1):11-18. doi: 10.4103/bc.bc_58_19. eCollection 2020 Jan-Mar.
citation: An JQ, Cheng YW, Guo YC, Wei M, Gong MJ, Tang YL, Yuan XY, Song WF, Mu CY, Zhang AF, Saguner AM, Li GL, Luo GG. Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke. Neurology. 2020 Dec 15;95(24):e3355-e3363. doi: 10.1212/WNL.0000000000010884. Epub 2020 Oct 7.