Intracerebral HemorrhagePhase 3RICH-2NCT04657133
Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage
A Phase 3 study testing Remote ischemic conditioning and Standard medication therapy in people with Intracerebral Hemorrhage and Acute Stroke, run by Capital Medical University at 13 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Intracerebral Hemorrhage, Acute Stroke
- What is being tested?
- Remote ischemic conditioning and Standard medication therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 452 participants
- Where
- 13 sitesChina
- Study dates
- 22 Apr 2021to 30 Jun 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
China13 sites, 10 recruiting
- Active, not recruiting
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 100053
- Active, not recruiting
Beijing Red Cross Emergency Rescue Center
Beijing, Beijing Municipality
- Not yet recruiting
Beijing Renhe Hospital
Beijing, Beijng
Na Li, M.D.
- Recruiting
The First People's Hospital of Changzhou
Changzhou, Jiangsu
Song Yang, M.D.
- Recruiting
Chengde Central Hospital
Chengde, Hebei
Jiangtao Zhang
- Recruiting
The Six People's Hospital of Hengshui
Hengshui, Hebei
Xinjing Gao
- Not yet recruiting
Jiaxing Second Hospital
Jiaxing, Zhejiang
Jianguo Shen
- Recruiting
Nanshi Hospital of Nanyang
Nanyang, Henan
Rongyao Ma
- Recruiting
Shaoxing People's Hospital
Shaoxing, Zhejiang, 312000
Xuebin Yu, MD
- Recruiting
Tianjin Huanhu Hospital
Tianjin, Tianjin Municipality, 300350
Ming Wei, MD
- Not yet recruiting
Tongliao Municipal Hosptial
Tongliao, Inner Mongolia
Yaoming Xu, M.D.
- Recruiting
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu
Deqin Geng, MD
- Active, not recruiting
Zhuji People's Hospital of Zhejaing Province
Zhuji, Zhejiang
About this study
Official title: The Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Multicenter, Randomized, Controlled Study
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
- Being tested
- Remote ischemic conditioning, Sham remote ischemic conditioning, Standard medication therapy
- Keywords
- Therapy, Neuroprotection
- Medical subject headings
- Cerebral Hemorrhage, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic conditioningDevice
Also called RIC
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.
Sham remote ischemic conditioningDevice
Also called Sham RIC
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.
Standard medication therapyDrug
Standard medication therapy will be performed according to the national and international guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Subjects in the intervention group will receive remote ischemic conditioning and standard background medical treatment. Receives: 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. Receives: Device: Sham remote ischemic conditioning; Drug: Standard medication therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0-90 days.
Secondary outcomes (5)
Proportion of Patients With mRS Score 0-3 at 90 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-3 at 90 days.
Measured: 90 days
Proportion of Patients With mRS Score 0-2 at 180 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-2 at 180 days.
Measured: 180 days
Proportion of Patients With mRS Score 0-3 at 180 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-3 at 180 days.
Measured: 180 days
Number of Subjects Experiencing Serious Adverse Events
Number of subjects experiencing Serious adverse events at any time from randomization through day 90
Measured: 90 days
Number of Subjects With Serious Adverse Events Within 7 Days
Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start22 Apr 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion30 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Intracerebral HemorrhageStudies of the same condition, open and under way.
- More trials run by Capital Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 452 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Capital Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ji Xunming,MD,PhD, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04657133
- Sponsor's protocol ID
- RICH-2
- Acronym
- RICH-2
- Status last verified
- Jul 2022
- First submitted
- 1 Dec 2020
- Last updated
- 19 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33174815Hemphill 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.
PubMed 26022637Zhao 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.
PubMed 33739197Zhao W, Wang J, Yu X, Wu G, Yang S, Lu D, Gao X, He Y, Niu L, Zhou H, Xuan C, Li N, Zhong M, Zhang J, Dong Q, Geng X, Ma Q, Song H, Yin Y, Liu L, Hess DC, Anderson CS, Li S, Ji X; RICH-2 Investigators. Remote ischaemic conditioning in patients with supratentorial intracerebral haemorrhage (RICH-2): a multicentre, randomised, sham-controlled phase 3 trial in China. EClinicalMedicine. 2026 Apr 13;95:103900. doi: 10.1016/j.eclinm.2026.103900. eCollection 2026 May.
PubMed 42011250
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Multicenter, Randomized, Controlled Study
- ClinicalTrials.gov ID
- NCT04657133
- Acronym / sponsor ID
- RICH-2 / RICH-2
- Conditions
- Intracerebral Hemorrhage, Acute Stroke
- Keywords
- Therapy, Neuroprotection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 452 participants (estimated)
- Lead sponsor
- Capital Medical UniversityUniversity, hospital or other
- Study start
- 22 Apr 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 30 Jun 2023 (estimated)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Device: Remote ischemic conditioning, Drug: Standard medication therapySubjects in the intervention group will receive remote ischemic conditioning and standard background medical treatment. |
| Sham group | Placebo comparator | Device: Sham remote ischemic conditioning, Drug: Standard medication therapySubjects in the placebo group will receive sham remote ischemic conditioning and standard background medical treatment alone. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote ischemic conditioningAlso: RICRIC 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. | Device | Intervention group |
| Sham remote ischemic conditioningAlso: Sham RICSham 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. | Device | Sham group |
| Standard medication therapyStandard medication therapy will be performed according to the national and international guidelines. | Drug | Intervention group, Sham group |
Primary outcome
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days
Time frame: 0-90 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.
5 secondary outcomes
Proportion of Patients With mRS Score 0-3 at 90 Days
Time frame: 90 days
Proportion of Patients With mRS Score 0-2 at 180 Days
Time frame: 180 days
Proportion of Patients With mRS Score 0-3 at 180 Days
Time frame: 180 days
Number of Subjects Experiencing Serious Adverse Events
Time frame: 90 days
Number of Subjects With Serious Adverse Events Within 7 Days
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2022.
- Background: PubMed 33174815Shoamanesh 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.
- Background: PubMed 26022637Hemphill 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.
- Background: PubMed 33739197Zhao 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.
- Derived from this study: PubMed 42011250Zhao W, Wang J, Yu X, Wu G, Yang S, Lu D, Gao X, He Y, Niu L, Zhou H, Xuan C, Li N, Zhong M, Zhang J, Dong Q, Geng X, Ma Q, Song H, Yin Y, Liu L, Hess DC, Anderson CS, Li S, Ji X; RICH-2 Investigators. Remote ischaemic conditioning in patients with supratentorial intracerebral haemorrhage (RICH-2): a multicentre, randomised, sham-controlled phase 3 trial in China. EClinicalMedicine. 2026 Apr 13;95:103900. doi: 10.1016/j.eclinm.2026.103900. eCollection 2026 May.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Remote ischemic conditioning and Standard medication therapy in people with Intracerebral Hemorrhage and Acute Stroke, run by Capital Medical University at 13 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xunming Ji, MD, PhD (010-83199430, jixm@ccmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days (time frame: 0-90 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04657133, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2022.