Clinical trial NCT03930940: Remote Ischemic Conditioning for Intracerebral Hemorrhage
Official title: Safey and Efficacy of Remote Ischemic Conditioning in Patient With Spontaneous Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Intracerebral Hemorrhage
Keywords: Spontenous intracerebral hemorrhage
Hemorrhage resolution
Remote ischemic conditioning
Neuroprotection
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Heze Municipal Hospital
name: The Sixth People's Hosptial of Hengshui
name: Weihai Municipal Hospital
First posted: 2019-04-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Spontaneous intracerebral hemorrhage (ICH) results from the rupture of small vessels damaged by chronic hypertension, amyloid angiopathy or other disease. Hematoma volume has been demonstrated to be strongly correlated with the severity of white matter injury and conditions in ICH patients. In the past decades, surgical clot evacuation and stereotactic or endoscopic clot aspiration with thrombolytic drugs have been investigated for the treatment of ICH, however, none of them have been demonstrated to be effective. As such, medical management remains the standard of care for most patients with ICH, leading to ICH as the least treatable form of stroke.

Remote ischemic conditioning (RIC) 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. Therefore, the investigators plan to undertake this study to evaluate the safety of RIC in patients with ICH, and planned for future study to determine if treatment with RIC can improve the outcome of patients with ICH.

In this study, our main objectives are: 1) to evaluated the safety of RIC, by determining the treatment related adverse events, in patients with ICH; and 2) to determine the preliminary effects of RIC on hematoma absorption and cerebral edema.

The investigators hypothesize that RIC is well-tolerated and has minimal serious adverse effects in patients with ICH; and 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.


Eligibility criteria: Inclusion Criteria:

1. Age≥18 and ≤80.
2. The diagnosis of ICH is confirmed by brain CT scan.
3. Hematoma volume of 10 to 30 ml.
4. Glasgow Coma Score (GCS)\>8.
5. Starting RIC treatment between 24 and 48 hours of ictus.
6. Signed and dated informed consented is obtained.

Exclusion Criteria:

1. Patients with suspected secondary ICH related to tumor, coagulopathy, ruptured aneurysm or arteriovenous malformation, or venous sinus thrombosis.
2. ICH concomitant with subarachnoid hemorrhage or intraventricular hemorrhage. Planned surgical evacuation of hematoma prior to RIC.
3. Evidence of significant shift of midline brain structure (\> 10 mm) or herniation on brain imaging.
4. Known pregnancy (or positive pregnancy test), or breast-feeding.
5. Concurrent participation in another research protocol for investigation of another experimental therapy.
6. Patients with a pre-existing neurological deficits (modified Ranks scale score \>1) or psychiatric disease that would confound the neurological or functional evaluations.
7. Life expectancy of less than 90 days due to co-morbid conditions.
8. Severe hepatic and renal dysfunction.
9. Severe, sustained hypertension (SBP \> 180 mmHg or DBP \> 110 mmHg).
10. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
11. Any condition which, in the judgment of the investigator, might increase the risk to the patient.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety]
timeFrame: 7 days.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Capital Medical Univeristy
name: Xunming Ji, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Zhao W, Zhang J, Sadowsky MG, Meng R, Ding Y, Ji X. Remote ischaemic conditioning for preventing and treating ischaemic stroke. Cochrane Database Syst Rev. 2018 Jul 5;7(7):CD012503. doi: 10.1002/14651858.CD012503.pub2.
citation: Zhao W, Che R, Li S, Ren C, Li C, Wu C, Lu H, Chen J, Duan J, Meng R, Ji X. Remote ischemic conditioning for acute stroke patients treated with thrombectomy. Ann Clin Transl Neurol. 2018 Jun 6;5(7):850-856. doi: 10.1002/acn3.588. eCollection 2018 Jul.
citation: Zhao W, Li S, Ren C, Meng R, Jin K, Ji X. Remote ischemic conditioning for stroke: clinical data, challenges, and future directions. Ann Clin Transl Neurol. 2018 Nov 15;6(1):186-196. doi: 10.1002/acn3.691. eCollection 2019 Jan.
citation: 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.
citation: Zhao W, Jiang F, Li S, Wu C, Gu F, Zhang Q, Gao X, Gao Z, Song H, Wang Y, Ji X; RICH-1 Investigators. Remote Ischemic Conditioning for Intracerebral Hemorrhage (RICH-1): Rationale and Study Protocol for a Pilot Open-Label Randomized Controlled Trial. Front Neurol. 2020 Apr 28;11:313. doi: 10.3389/fneur.2020.00313. eCollection 2020.