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

Overview

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.

Interventions

• Device 14-day remote ischemic conditioning
  RIC is a noninvasive therapy performed by an electric auto-control device with a cuff placed on the upper arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of the cuff on the upper arm. The procedure will be performed once before endovascular thrombectomy and twice daily for 14 days post-thrombectomy.
• Device 30-day remote ischemic conditioning
  RIC is a noninvasive therapy performed by an electric auto-control device with a cuff placed on the upper arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of the cuff on the upper arm. The procedure will be performed once before endovascular thrombectomy and twice daily for 30 days post-thrombectomy.
• Procedure Endovascular thrombectomy
  Endovascular thrombectomy procedures are performed according to the guidelines to recanalize the occluded large vessel safely.
• Drug Best medical management
  Best medical management is prescribed at the discretion of the treating physicians according to the guidelines.

Primary outcome measures

• The proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days. [Time frame: 90 days after stroke.]

Secondary outcome measures (12)

• 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). [Time frame: 90 days after stroke.]
• The ordinal distribution of mRS scores at 90 days. [Time frame: 90 days after stroke.]
• The proportion of patients with early neurological improvement 24 hours after endovascular procedures. [Time frame: 24 hours after endovascular procedures.]
• Changes in NIHSS score from baseline to day 14 or at discharge (whichever comes earlier). [Time frame: 14 days or at discharge (whichever comes first)]
• Score of EQ-5D-5L at 90 days. [Time frame: 90 days after stroke.]
• Cerebral infarct volume. [Time frame: 72 hours after endovascular procedures.]
• The change of infarct volume. [Time frame: 72 hours after endovascular procedures.]
• Incidence of intracranial hemorrhage. [Time frame: Within 14 days after endovascular procedures.]
• Incidence of Symptomatic Intracranial Hemorrhage [Time frame: Within 14 days after endovascular procedures.]
• Incidence of neurological deterioration within 14 days. [Time frame: Within 14 days after endovascular procedures.]
• Incidence of malignant infarction [Time frame: 0-90 days]
• All cause of death. [Time frame: 0-90 days]

Eligibility criteria

Inclusion criteria

• Age≥18 years；
• 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;
• 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;
• Baseline score of the National Institutes of Health Stroke Scale (NIHSS) ≥ 6 points;
• Patients or family members signed a written informed consent form.

Exclusion criteria

• 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);
• 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;
• Difficult-to-control hypertension: continuous monitoring upon admission shows systolic blood pressure ≥180mmHg, or diastolic blood pressure ≥100mmHg;
• Coma or lethargy patients (consciousness level score ≥2 in NIHSS);
• Unable to obtain an accurate baseline NIHSS score;
• Pre-stroke modified Rankin Scale (mRS) score >1;
• Baseline ASPECTS score ≤5;
• Presence of bleeding tendency, deficiency of coagulation factors, or oral anticoagulant therapy with INR > 3.0;
• Baseline blood glucose <2.7mmol/L or >22.2mmol/L;
• Baseline platelet count < 30\*10\^9/L;
• Severe known renal impairment defined as requiring dialysis (hemodialysis or peritoneal dialysis), or if known creatinine clearance rate <30mL/min;
• Cranial CT or MRI shows intracranial hemorrhage;
• Cranial CT or MRI shows midline deviation and significant occupying effect;
• Clinical history, previous imaging examinations, or clinical judgment suggesting intracranial tumors, arteriovenous malformations, or intracranial arterial dissection;
• History of head injury in the past 3 months;
• History of life-threatening allergy to contrast agents, nickel, titanium metal, or their alloys;
• Pregnancy, if women of childbearing age have a positive urinary or serum β-human chorionic gonadotropin (β-hCG) test or are breastfeeding；
• The life expectancy of patients is less than 6 months, and they cannot be evaluated within 3 months;
• Limb deformity, soft tissue injury, or other conditions that affect the implementation of distant ischemia adaptation therapy;
• Participating in other ongoing clinical trials;
• Other conditions that the investigators believe are not suitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 56 centers

• Suzhou Municipal Hospital of Anhui Province — Suzhou
• Taihe County People's Hospital — Taihe Chengguanzhen
• Tongling People's Hospital — Tongling
• Beijing Luhe Hospital affiliated to Capital Medical University — Beijing
• Beijing Fangshan District First Hospital — Beijing
• Fujian Provincial Hospital — Fuzhou
• Zhangzhou Municipal Hospital of Fujian Province — Zhangzhou
• Shenzhen Second People's Hospital — Shenzhen
• … and 48 more centers

Publications

• 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/CIRCULATIO PMID 28174194
• 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. PMID 32166195
• 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. PMID 33028663
• Wang Y, Huang S, Liu L, Ji X, Zhao W, Li S; RECAST-MT investigators. Safety and Efficacy of Remote Ischaemic Conditioning for Acute Ischaemic Stroke Treated with Mechanical Thrombectomy (RECAST-MT): rationale and design. Stroke Vasc Neurol. 2025 Nov 25:svn-2025-004591. doi: 10.1136/svn-2025-004591. Online ahead of print. PMID 41290408

Identifiers

NCT: NCT06559241 · RECAST-MT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗