Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage

NCT04657133 | Unknown Phase 3 DMC

• 1 other identifier: RICH-2
• Study Type: interventional
• Target: 452
• Locations: 1 country
• Sites: 13

Brief Summary

Intracerebral hemorrhage (ICH) results from the rupture of small vessels damaged by chronic hypertension, amyloid angiopathy or other disease. Currently, ICH has been a devastating type of stroke that lacking effective therapy. Remote ischemic conditioning (RIC), a systematically protective strategy, has been found to have neuroprotective effects by in patients with ischemic stroke. In addition, animal studies show that RIC is safe in ICH model and it could accelerate the absorption of hematoma. In a previous clinical study (RICH-1), RIC have been found to be safe and well-tolerated in patients with ICH. Therefore, the investigators plan to undertake this study to further evaluate the safety and efficacy of RIC in patients with ICH. The investigators hypothesize that treatment with RIC will accelerate the absorption of hematoma and improve patients' functional outcomes. Results of this study can potentially bring into account new means to improve the outcomes of ICH patients.

Conditions

Intracerebral Hemorrhage; Acute Stroke

Keywords

Therapy; Neuroprotection

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days

  The mRS ranges from 0 to 6, with higher scores indicating worse outcome. The primary outcome measure is the mRS score, dichotomized to define favorable functional outcome as mRS 0-2 at 90 days.

  0-90 days.

Secondary Outcomes (5)

• Proportion of Patients With mRS Score 0-3 at 90 Days

  90 days

• Proportion of Patients With mRS Score 0-2 at 180 Days

  180 days

• Proportion of Patients With mRS Score 0-3 at 180 Days

  180 days

• Number of Subjects Experiencing Serious Adverse Events

  90 days

• Number of Subjects With Serious Adverse Events Within 7 Days

  7 days

Other Outcomes (4)

• Changes of intracerebral hematoma volume

  0-7 days after enrollment.

• Changes of perihematomal edema volume

  0-7 days after enrollment.

• Ordinal Distribution of Scores on mRS at Day 90

  90 days

Study Arms (2)

Intervention group

EXPERIMENTAL

Subjects in the intervention group will receive remote ischemic conditioning and standard background medical treatment.

Device: Remote ischemic conditioning; Drug: Standard medication therapy

Sham group

PLACEBO COMPARATOR

Subjects in the placebo group will receive sham remote ischemic conditioning and standard background medical treatment alone.

Device: Sham remote ischemic conditioning; Drug: Standard medication therapy

Interventions

Remote ischemic conditioning DEVICE

RIC is a non-invasive therapy that performed by an electric autocontrol device with cuff placed on arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuff on one arm. The procedure will be performed once daily for consecutive 7 days after enrollment.

Also known as: RIC

Intervention group

Sham remote ischemic conditioning DEVICE

Sham RIC will be performed by the same electric autocontrol device with cuff placed on arm. Sham RIC procedures consist of five cycles of 5-min inflation (30 mmHg) and 5-min deflation of cuff on one arm. The procedure will be performed once daily for consecutive 7 days after enrollment.

Also known as: Sham RIC

Sham group

Standard medication therapy DRUG

Standard medication therapy will be performed according to the national and international guidelines.

Intervention group; Sham group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 and ≤ 80 years
• The diagnosis of supratentorial ICH is confirmed by brain CT scan
• Hematoma volume of 10 to 30 ml and Glasgow Coma Score (GCS)\>8 at randomization.
• National Institutes of Health Stroke Scale (NIHSS)≥6 and ≤20 points at randomization.
• Randomization and starting treatment between 24 and 48 hours of symptom ictus.
• Signed and dated informed consent is obtained.

You may not qualify if:

• Planned surgical evacuation of ICH prior to administration of investigational intervention
• ICH concomitant with subarachnoid hemorrhage or intraventricular hemorrhage
• Suspected secondary ICH related to tumor, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
• Patients with a pre-existing neurological deficit (mRS\>1) or psychiatric disease that would confound the neurological or functional evaluations.
• Coagulopathy - defined as elevated aPTT or INR \>1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban or apixaban), or low-molecular-weight heparin
• Severe renal disease (i.e., renal disorder requiring dialysis ) or eGFR \<30ml/min/1.73m2
• Severe liver disorder, or ALT \>3 times or bilirubin \>2 times upper limit of normal
• Known severe hearing loss or cognitive impairment
• Known pregnancy, or positive pregnancy test, or breastfeeding
• Patients known or suspected of not being able to comply with the study protocol due to alcoholism, noncompliance or any other cause
• Life expectancy of less than 90 days due to co-morbid conditions
• Concurrent participation in another research protocol for investigation of another experimental therapy
• Severe, sustained hypertension (Systolic blood pressure\> 180 mmHg or diastolic blood pressure\> 110 mmHg).
• Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
• Any condition which, in the judgement of the investigator, might increase the risk to the patient.

Sponsors & Collaborators

• Capital Medical University: lead

Study Sites (13)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

ACTIVE NOT RECRUITING

Beijing Red Cross Emergency Rescue Center

Beijing, Beijing Municipality, China

ACTIVE NOT RECRUITING

Beijing Renhe Hospital

Beijing, Beijng, China

NOT YET RECRUITING

Chengde Central Hospital

Chengde, Hebei, China

RECRUITING

The Six People's Hospital of Hengshui

Hengshui, Hebei, China

RECRUITING

Nanshi Hospital of Nanyang

Nanyang, Henan, China

RECRUITING

Tongliao Municipal Hosptial

Tongliao, Inner Mongolia, China

NOT YET RECRUITING

The First People's Hospital of Changzhou

Changzhou, Jiangsu, China

RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

RECRUITING

Tianjin Huanhu Hospital

Tianjin, Tianjin Municipality, 300350, China

RECRUITING

Jiaxing Second Hospital

Jiaxing, Zhejiang, China

NOT YET RECRUITING

Shaoxing People's Hospital

Shaoxing, Zhejiang, 312000, China

RECRUITING

Zhuji People's Hospital of Zhejaing Province

Zhuji, Zhejiang, China

ACTIVE NOT RECRUITING

Related Publications (3)

• Shoamanesh A, Patrice Lindsay M, Castellucci LA, Cayley A, Crowther M, de Wit K, English SW, Hoosein S, Huynh T, Kelly M, O'Kelly CJ, Teitelbaum J, Yip S, Dowlatshahi D, Smith EE, Foley N, Pikula A, Mountain A, Gubitz G, Gioia LC. Canadian stroke best practice recommendations: Management of Spontaneous Intracerebral Hemorrhage, 7th Edition Update 2020. Int J Stroke. 2021 Apr;16(3):321-341. doi: 10.1177/1747493020968424. Epub 2020 Nov 11.

  PMID: 33174815 BACKGROUND

• Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60. doi: 10.1161/STR.0000000000000069. Epub 2015 May 28.

  PMID: 26022637 BACKGROUND

• Zhao W, Jiang F, Li S, Liu G, Wu C, Wang Y, Ren C, Zhang J, Gu F, Zhang Q, Gao X, Gao Z, Song H, Ma Q, Ding Y, Ji X; RICH-1 Investigators. Safety and efficacy of remote ischemic conditioning for the treatment of intracerebral hemorrhage: A proof-of-concept randomized controlled trial. Int J Stroke. 2022 Apr;17(4):425-433. doi: 10.1177/17474930211006580. Epub 2021 Apr 7.

  PMID: 33739197 BACKGROUND

MeSH Terms

Conditions

Cerebral Hemorrhage; Stroke

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Xunming Ji, MD, PhD

CONTACT

010-83199430; jixm@ccmu.edu.cn

Wenbo Zhao, MD, PhD

CONTACT

86-13120136877; zhaowb@xwh.ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 8, 2020
• Study Start: April 22, 2021
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2023
• Last Updated: July 19, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (13)