Remote ischemic preconditioning to prevent early worsening after small deep (perforating artery) ischemic stroke

Effect of Remote Ischemic Preconditioning on Early Neurological Deterioration in Acute Perforating Artery Infarction (RIC-END): A Randomised Multicentre Trial

This trial will test whether brief, repeated arm blood-pressure cuff inflations (remote ischemic preconditioning) can prevent early neurological worsening in adults who have had a small deep perforating artery ischemic stroke within 48 hours.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 910 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jinling Hospital, China (Academic / other)
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07237542 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, double-blind, multicenter, parallel-controlled, group-sequential trial comparing remote ischemic preconditioning (RIC) to a sham procedure in a 1:1 allocation. Adults with acute perforating artery infarction within 48 hours, low NIHSS scores, and a single small DWI-confirmed lesion are enrolled and treated with repeated brief limb ischemia or sham. The primary focus is on preventing early neurological deterioration (an increase of ≥2 points on the NIHSS within 7 days) with monitoring of safety and clinical outcomes. The trial aims to provide rigorous evidence on whether RIC reduces early worsening and improves short-term neurological status in this specific stroke subtype.

Who should consider this trial

Good fit: Adults (≥18) with acute perforating artery infarction within 48 hours, NIHSS ≤5, a single DWI lesion meeting the size/location criteria and parent artery stenosis <70%, who have not received thrombolysis or endovascular therapy, are the intended participants.

Not a fit: Patients with large cortical strokes, intracranial hemorrhage, secondary stroke causes, prior reperfusion therapy, severe deficits outside the inclusion criteria, or presentation beyond 48 hours are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, RIC could reduce early neurological deterioration and lower short-term disability after small deep perforating artery strokes.

How similar studies have performed: Small physiological and pilot clinical studies have suggested RIC can protect ischemic brain tissue, but large randomized trials specifically in acute perforating artery infarction are lacking.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older;
2. Diagnosed with acute ischemic stroke;
3. Clinical symptoms consistent with perforating artery infarction (NIHSS score ≤5, with consciousness item 1a ≤1);
4. Time from onset to randomization within 48 hours;
5. Diffusion-weighted imaging (DWI) showing a single infarct in the perforating artery territory with a maximum diameter ≤30 mm, meeting at least one of the following:

(1) Diameter ≤15 mm and involving two or more axial slices; (2) Maximum diameter ≥15 mm; (3) Connected to the ventral surface of the pons but not crossing the midline; 6) Stenosis of parent artery \<70%; 7) Signed informed consent obtained from the patient or their legally authorized representative.

Exclusion Criteria:

1. Received intravenous thrombolysis or endovascular treatment prior to randomization;
2. Secondary stroke caused by brain tumor, traumatic brain injury, hematologic disorders, or other conditions;
3. History of intracranial hemorrhage;
4. Presence of RIC contraindications, such as severe upper limb soft tissue injury, fracture, subclavian artery stenosis, or peripheral vascular disease;
5. Uncontrolled severe hypertension (systolic blood pressure \[BP\] ≥180 mmHg or diastolic BP ≥110 mmHg);
6. Severe hepatic or renal dysfunction (Alanine Aminotransferase or Aspartate Aminotransferase \> 3 × upper limit of normal; creatine kinase \>3 × upper limit of normal; estimated Glomerular Filtration Rate \< 30 mL / min / 1.73 m²);
7. Patients with thrombocytopenic purpura, coagulation disorders, or active visceral bleeding;
8. Patients in the acute phase of fundus hemorrhage;
9. History of severe aphasia or psychiatric disorders affecting clinical assessment;
10. Life expectancy \<90 days;
11. Pregnancy;
12. Inability to comply with follow-up;
13. Participation in other clinical trials.

Where this trial is running

Nanjing, Jiangsu

• Jinling Hospital, Medical School of Nanjing University, Nanjing — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wusheng Zhu, PhD

Conditions Ischemic Stroke; Remote Ischaemic Preconditioning; perforating artery stroke; remote ischemic preconditioning; early neurological deterioration; randomized controlled trial