Safety and Efficacy of Remote Ischemic Conditioning for Spontaneous Intracerebral Hemorrhage

The purpose of this study is to determine the efficacy and safety of remote ischemic conditioning in treating acute intracerebral hemorrhage.

Study Overview

• Status: Recruiting
• Conditions: Intracranial Hemorrhages
• Intervention / Treatment: Device: Remote ischemic conditioning; Device: Sham remote ischemic conditioning

Detailed Description

Spontaneous intracerebral hemorrhage is a major cause of disability and mortality among different types of stroke, and few effective treatment options are available. Therefore, it is essential to develop new approaches to improve the prognosis of these patients. Recently, remote ischemic conditioning (RIC), a method that involves inducing multiple brief episodes of ischemia and reperfusion in the limbs, has been indicated to exert neuroprotective effects in experimental stroke. The underlying neuroprotective mechanism triggered by RIC induces gene expression, alters pathways, promotes neurogenesis and blood vessel development, reduces oxidative stress and neuronal apoptosis, and inhibits proinflammatory signals. Previously, several clinical trials have shown that single or repeated RIC treatments for cerebrovascular diseases are feasible and safe. Therefore, we hypothesize that RIC could improve functional outcome in patients with intracerebral hemorrhage. We design this prospective, multicenter, randomized controlled trial to evaluate the efficacy and safety of RIC in treating intracerebral hemorrhage.

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi Yang, MD, PhD; Phone Number: 0086 13756661217; Email: doctoryangyi@163.com
• Study Contact Backup: Name: Zhenni Guo, MD, PhD; Phone Number: 0086 18186872986; Email: zhen1ni2@163.com

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • First Hospital of Jilin University
      • Contact: Yi Yang, MD, PhD; Phone Number: +86-18186870008; Email: doctoryangyi@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years.
2. Supratentorial intracerebral hemorrhage confirmed by brain CT scan.
3. No disability in the community before ICH (premorbid mRS≤ 1).
4. NIHSS score ≥ 6 and GCS ≥ 8 upon presentation.
5. Able to commence RIC treatment within 24 hours of stroke onset.
6. Systolic blood pressure ≤ 180 mmHg before randomization.
7. Signed and dated informed consent is obtained.

Exclusion Criteria:

1. Definite evidence of secondary ICH, such as structural abnormality, brain aneurysm, brain tumor, thrombolytic drug.
2. Hematoma with a mid-line shift, cerebral herniation or isolate intraventricular hemorrhage.
3. Already booked for surgical treatment.
4. Life expectancy of less than 180 days due to comorbid conditions.
5. Concurrent use of anticoagulation drugs including Warfarin, dabigatran, rivaroxaban or coagulopathy (defined as INR, APTT, and PT beyond the upper limit of normal range).
6. Any soft tissue, orthopedic, or vascular injury, wounds or fractures in healthy upper limb which may pose a contraindication for application of RIC.
7. Severe hepatic and renal dysfunction, or ALT/AST >3 times upper limit of normal, or serum creatinine >265umol/l.
8. Known pregnancy or breastfeeding.
9. Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial.
10. A high likelihood that the patient will not adhere to the study treatment and follow up regimen.
11. Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RIC group; Remote ischemic conditioning (RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg.	Device: Remote ischemic conditioning; Remote ischemic conditioning is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg.
Placebo Comparator: Sham RIC group; Sham remote ischemic conditioning (Sham RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 60 mm Hg.	Device: Sham remote ischemic conditioning; Remote ischemic conditioning is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 60 mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 at 180 days	Proportion of patients with Modified Rankin Scale (mRS) Score 0-2. Ranged from 0 to 6, a low value represents a better outcome.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 at 90 days	Proportion of patients with Modified Rankin Scale (mRS) Score 0-2. Ranged from 0 to 6, a low value represents a better outcome.	90 days
Ordinal shift of the full range of mRS scores at 90 and 180 days	Ranged from 0 to 6, a low value represents a better outcome.	90 days, 180 days
Hematoma growth at 24 hours	The growth in hematoma volume after the onset of intracerebral hemorrhage, which is assessed by Computed Tomography (CT) brain scan.	24 hours
National Institute of Health stroke scale (NIHSS) at 7 days	National Institute of Health stroke scale (NIHSS) ranged from 0 to 42, a low value represents a better outcome.	7 days
Adverse events occurring in the course of the study.	The safety endpoints will include all adverse events, severe adverse events and RIC related adverse events.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracerebral hematoma volume at 7 days	Intracerebral hematoma volume is assessed by Computed Tomography (CT) brain scan.	0-7 days
Hematoma absorption at 7 days	Hematoma absorption is assessed by Computed Tomography (CT) brain scan.	0-7 days
National Institute of Health stroke scale (NIHSS) at 7 days	National Institute of Health stroke scale (NIHSS) ranged from 0 to 42, a low value represents a better outcome.	0-7 days
Glasgow Coma Scale (GCS) at 7 days	Glasgow Coma Scale (GCS) ranged from 3 to 15, a high value represents a better outcome.	0-7 days
Hematological indicators at 7 days	The changes of hematological indicators.	7 days

Collaborators and Investigators

• Sponsor: Yi Yang

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2023
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: November 2, 2022
• First Submitted That Met QC Criteria: November 6, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; Intracranial Hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemorrhage; Intracranial Hemorrhages; Cerebral Hemorrhage
• Other Study ID Numbers: SERIC-ICH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No