Ischemic Stroke, Remote Ischaemic Preconditioning
Conditions
Keywords
perforating artery stroke, remote ischemic preconditioning, early neurological deterioration, randomized controlled trial
Brief summary
This study aims to conduct a prospective, randomized, double-blind, multicenter, parallel-controlled, group-sequential trialto scientifically evaluate the safety and efficacy of remote ischemic preconditioning (RIC) in preventing early neurological deterioration (END) in patients with acute perforating artery infarction (PAI).
Detailed description
Penetrating artery infarction (PAI) is a single small deep infarct within the territory of a perforating artery, accounting for 15.3%-25% of all ischemic strokes. Early neurological deterioration (END) is a critical factor contributing to poor prognosis in PAI. END is generally defined as an increase of ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days after stroke onset. Remote ischemic preconditioning (RIC) involves repeated, low-intensity ischemic training of both upper limbs to enhance the resistance of organs to severe ischemic injury. RIC confers protective effects on ischemic brain tissue and may serve as a new therapeutic approach for intracranial atherosclerosis and acute cerebral infarction. However, large-scale randomized controlled trials evaluating the clinical efficacy of RIC in acute PAI are lacking. Therefore, this study aims to conduct a multicenter, prospective, randomized clinical trial to scientifically assess the clinical efficacy of RIC in patients with acute PAI, providing evidence-based support for its application in this population. In this trial, patients with acute PAI (within 48 hours from onset to randomization) will be included. In the screening stage, participants who meet the trial's inclusion criteria-after completing screening/baseline assessment and signing the informed consent-will be randomly assigned in a 1:1 ratio to one of the following two treatment groups: the experimental group will receive RIC (200 mmHg), and the control group will receive sham RIC (60 mmHg). The primary end point is the incidence of END within 5 days after randomization.
Interventions
DEVICEremote ischemic preconditioning
The standard RIC procedure involves placing a blood pressure cuff on both upper limbs, rapidly inflating the cuff to occlude arterial blood flow and induce transient limb ischemia, followed by deflating the cuff to restore blood perfusion. RIC is administered twice daily on both upper limbs, with each session consisting of 5 cycles, for 5-7 consecutive days. The inflation pressure for RIC treatment is set at 200 mmHg.
The standard RIC procedure involves placing a blood pressure cuff on both upper limbs, rapidly inflating the cuff to occlude arterial blood flow and induce transient limb ischemia, followed by deflating the cuff to restore blood perfusion. RIC is administered twice daily on both upper limbs, with each session consisting of 5 cycles, for 5-7 consecutive days. The inflation pressure for RIC treatment is set at 60 mmHg.
Sponsors
Jinling Hospital, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open label, blinded outcome assessment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of early neurological deterioration | 5 days after randomization | an increase of ≥2 points in the National Institutes of Health Stroke Scale (NIHSS), including an increase of ≥1 point in the motor score. NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of early neurological deterioration | 2 days after randomization | an increase of ≥2 points in the National Institutes of Health Stroke Scale (NIHSS), including an increase of ≥1 point in the motor score. NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits). |
| Proportion of patients with a modified Rankin Scale score of 0-1 | 90 days after randomization | modified Ranking score: ranging from 0 to 6, with higher values indicating a worse functional outcome. |
| The incidence of early neurological improvement | 5 days after randomization | defined as a decrease of ≥2 points in National Institutes of Health Stroke Scale (NIHSSS). NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits). |
| The incidence of major adverse cardiovascular events | 90 days after randomization | Major adverse cardiovascular events (MACE) refers to a composite measure of serious cardiovascular complications, typically including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, sometimes also encompassing hospitalization for unstable angina or urgent revascularization. |
| Barthel Index | 90 days after randomization | Barthel Index is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis) |
| EuroQol 5-Dimension 5-Level Questionnaire score | 90 days after randomization | The EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L score) is a standardized index measuring a person's overall health-related quality of life, based on five dimensions-mobility, self-care, usual activities, pain/discomfort, and anxiety/depression-each rated on five levels of severity. EQ-5D-5L scores range from -0.59 to 1, where 1 is the best possible health state. |
Countries
China
Contacts
CONTACTWusheng Zhu, PhD
Outcome results
None listed