Efficacy and Safety of Minocycline in Acute Spontaneous Intracerebral Hemorrhage

NCT ID: NCT07338175

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-12-31

Brief Summary

This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. It aims to evaluate the efficacy and safety of oral minocycline in patients with acute spontaneous intracerebral hemorrhage within 48 hours of onset.

Detailed Description

The aim of this study was to evaluate the efficacy and safety of 5-day Minocycline versus placebo in patients with acute intracerebral hemorrhage within 48 hours of onset. In addition, we will explore the effect of Minocycline versus placebo on indicators of venous neuroinflammation at different time points in patients with acute intracerebral hemorrhage within 48 hours of onset.

A total of 1192 participants will be randomized 1:1 to receive either minocycline or matching placebo for 5 days, in addition to guideline-based standard medical care.

The primary objective is to evaluate the effect of Minocycline in improving the level of 90-day mRS score to 0-3 in patients with acute intracerebral hemorrhage within 48 hours of onset.

The trial is divided into three phases: screening/baseline period, treatment period, and follow-up period. The visit schedule is as follows: Randomized participants are interviewed at screening/baseline period, 72±12 hours, 7±1 days, 90±7 days,180±7 days after randomization, and when events occur.

Conditions

Intracerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Comparator: Minocycline treatment group

Minocycline Hydrochloride Capsules (50 mg per capsule). The first dose (200mg, 4 capsules) should be given immediately after randomization (within 30 minutes); Subsequently, 100mg (2 capsules) will be administered once every 12 hours; a total of 10 times (lasting 5 days; the subject with dysphagia will be administrated through a nasal feeding tube).

Group Type: EXPERIMENTAL

Minocycline hydrochloride capsules

Intervention Type: DRUG

50 mg per capsule, containing 50mg of Minocycline Hydrochloride

Placebo Comparator: Minocycline placebo-control group

Placebo of Minocycline Hydrochloride capsules (50mg per capsule, containing 0 mg of Minocycline). The method of administration was the same as that of treatment group.

Group Type: PLACEBO_COMPARATOR

Placebo capsules of Minocycline hydrochloride capsules

Intervention Type: DRUG

50 mg per capsule, containing 0 mg of Minocycline Hydrochloride

Interventions

Minocycline hydrochloride capsules

50 mg per capsule, containing 50mg of Minocycline Hydrochloride

Intervention Type: DRUG

Placebo capsules of Minocycline hydrochloride capsules

50 mg per capsule, containing 0 mg of Minocycline Hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. CT-confirmed spontaneous supratentorial intracerebral hemorrhage;

2. Aged 18 to 80 years;

3. Within 48 hours of symptom onset;

4. Hematoma volume 15-40 ml;

5. NIHSS score 8-24, with item 1a ≤ 2;

6. Signed informed consent by the patient or legal representative.

Exclusion Criteria

1. Secondary intracerebral hemorrhage (traumatic, tumor-related, vascular malformation, aneurysm, coagulation disorder, etc.);

2. Intraventricular hemorrhage filling one entire lateral ventricle, third ventricle, or fourth ventricle, or more than half of two lateral ventricles;

3. Significant subarachnoid hemorrhage (Fisher grade ≥ 3) or subdural hemorrhage;

4. Patients with uncontrollable hypertension or those at high risk of hematoma expansion indicated by imaging signs;

5. Progressive neurological or other severe systemic diseases;

6. Planned surgical intervention for the intracerebral hemorrhage;

7. Pre-stroke disability (modified Rankin Scale score > 1);

8. Severe cardiac insufficiency (NYHA Class III-IV), severe liver disease (ALT or AST > 3 times the normal upper limit value), severe renal insufficiency (serum creatinine > 2 times the normal upper limit value, or glomerular filtration rate < 45 ml/min), or malignancy with life expectancy < 1 year;

9. Moderate to severe anemia (hemoglobin < 90 g/L), thrombocytopenia (platelet count < 100×10^9/L), leukopenia (white blood cell count < 2×10^9/L), or coagulopathy (INR > 1.5);

10. Allergy or intolerance to minocycline or other tetracycline antibiotics;

11. History of pseudomembranous enteritis or antibiotic-associated enteritis;

12. Use of tetracycline antibiotics within the past week;

13. Intracranial or spinal surgery within the past 3 months;

14. Any major surgery or severe physical trauma within the past month;

15. Females who are pregnant, within 30 days postpartum, or in the lactation period.

16. Participated in other interventional clinical trials within the past 3 months;

17. Inability to obtain signed informed consent from the patient or representative;

18. Other conditions that are not suitable for participating in this clinical trial, such as inability to understand and/or follow the research procedures due to mental, cognitive, emotional, or physical disorders, etc.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xingquan Zhao

Xingquan Zhao; Yilong Wang

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Tiantan Hospital

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Kaijiang Kang, MD

Role: CONTACT

kangkaijiang678@126.com

+86 59975701

References

Bai Q, Xue M, Yong VW. Microglia and macrophage phenotypes in intracerebral haemorrhage injury: therapeutic opportunities. Brain. 2020 May 1;143(5):1297-1314. doi: 10.1093/brain/awz393.

Reference Type: RESULT

PMID: 31919518 (View on PubMed)

Xue M, Yong VW. Neuroinflammation in intracerebral haemorrhage: immunotherapies with potential for translation. Lancet Neurol. 2020 Dec;19(12):1023-1032. doi: 10.1016/S1474-4422(20)30364-1.

Reference Type: RESULT

PMID: 33212054 (View on PubMed)

Chang JJ, Kim-Tenser M, Emanuel BA, Jones GM, Chapple K, Alikhani A, Sanossian N, Mack WJ, Tsivgoulis G, Alexandrov AV, Pourmotabbed T. Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study. Eur J Neurol. 2017 Nov;24(11):1384-1391. doi: 10.1111/ene.13403. Epub 2017 Sep 20.

Reference Type: RESULT

PMID: 28929560 (View on PubMed)

Lu Y, Guan L, Zhang M, Yang Q, Qiu B, Zhou D, Wang Y, Pan Y, Wang L, Zhou X, Qu H, Liao X, Liu L, Zhao X, Bath PM, Johnston SC, Amarenco P, Wang Y, Wang Y. Rationale and Study Design to Assess the Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke (EMPHASIS). Stroke Vasc Neurol. 2025 Dec 23;10(6):786-792. doi: 10.1136/svn-2024-003577.

Reference Type: RESULT

PMID: 40147820 (View on PubMed)

Fouda AY, Newsome AS, Spellicy S, Waller JL, Zhi W, Hess DC, Ergul A, Edwards DJ, Fagan SC, Switzer JA. Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial. Stroke. 2017 Oct;48(10):2885-2887. doi: 10.1161/STROKEAHA.117.018658. Epub 2017 Sep 8.

Reference Type: RESULT

PMID: 28887388 (View on PubMed)

Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db.

Reference Type: RESULT

PMID: 17909152 (View on PubMed)

Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002 Mar 1;22(5):1763-71. doi: 10.1523/JNEUROSCI.22-05-01763.2002.

Reference Type: RESULT

PMID: 11880505 (View on PubMed)

Kraus RL, Pasieczny R, Lariosa-Willingham K, Turner MS, Jiang A, Trauger JW. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem. 2005 Aug;94(3):819-27. doi: 10.1111/j.1471-4159.2005.03219.x.

Reference Type: RESULT

PMID: 16033424 (View on PubMed)

Lee JM, Yin K, Hsin I, Chen S, Fryer JD, Holtzman DM, Hsu CY, Xu J. Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage. J Neurol Sci. 2005 Mar 15;229-230:249-54. doi: 10.1016/j.jns.2004.11.041. Epub 2004 Dec 29.

Reference Type: RESULT

PMID: 15760647 (View on PubMed)

Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13496-500. doi: 10.1073/pnas.96.23.13496.

Reference Type: RESULT

PMID: 10557349 (View on PubMed)

Garrido-Mesa N, Zarzuelo A, Galvez J. What is behind the non-antibiotic properties of minocycline? Pharmacol Res. 2013 Jan;67(1):18-30. doi: 10.1016/j.phrs.2012.10.006. Epub 2012 Oct 17.

Reference Type: RESULT

PMID: 23085382 (View on PubMed)

Fu Y, Hao J, Zhang N, Ren L, Sun N, Li YJ, Yan Y, Huang D, Yu C, Shi FD. Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol. 2014 Sep;71(9):1092-101. doi: 10.1001/jamaneurol.2014.1065.

Reference Type: RESULT

PMID: 25003359 (View on PubMed)

Puy L, Perbet R, Figeac M, Duchene B, Deramecourt V, Cordonnier C, Berezowski V. Brain Peri-Hematomal Area, a Strategic Interface for Blood Clearance: A Human Neuropathological and Transcriptomic Study. Stroke. 2022 Jun;53(6):2026-2035. doi: 10.1161/STROKEAHA.121.037751. Epub 2022 Apr 25.

Reference Type: RESULT

PMID: 35465695 (View on PubMed)

Li N, Guo J, Kang K, Zhang J, Zhang Z, Liu L, Liu X, Du Y, Wang Y, Zhao X. Cytotoxic Edema and Adverse Clinical Outcomes in Patients with Intracerebral Hemorrhage. Neurocrit Care. 2023 Apr;38(2):414-421. doi: 10.1007/s12028-022-01603-2. Epub 2022 Sep 30.

Reference Type: RESULT

PMID: 36180765 (View on PubMed)

Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet. 2018 Oct 6;392(10154):1257-1268. doi: 10.1016/S0140-6736(18)31878-6.

Reference Type: RESULT

PMID: 30319113 (View on PubMed)

Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, Hemphill JC 3rd, Johnson R, Keigher KM, Mack WJ, Mocco J, Newton EJ, Ruff IM, Sansing LH, Schulman S, Selim MH, Sheth KN, Sprigg N, Sunnerhagen KS; American Heart Association/American Stroke Association. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-e361. doi: 10.1161/STR.0000000000000407. Epub 2022 May 17. No abstract available.

Reference Type: RESULT

PMID: 35579034 (View on PubMed)

Wu TY, Sharma G, Strbian D, Putaala J, Desmond PM, Tatlisumak T, Davis SM, Meretoja A. Natural History of Perihematomal Edema and Impact on Outcome After Intracerebral Hemorrhage. Stroke. 2017 Apr;48(4):873-879. doi: 10.1161/STROKEAHA.116.014416. Epub 2017 Mar 8.

Reference Type: RESULT

PMID: 28275199 (View on PubMed)

Murthy SB, Moradiya Y, Dawson J, Lees KR, Hanley DF, Ziai WC; VISTA-ICH Collaborators. Perihematomal Edema and Functional Outcomes in Intracerebral Hemorrhage: Influence of Hematoma Volume and Location. Stroke. 2015 Nov;46(11):3088-92. doi: 10.1161/STROKEAHA.115.010054. Epub 2015 Sep 22.

Reference Type: RESULT

PMID: 26396030 (View on PubMed)

Sheth KN. Spontaneous Intracerebral Hemorrhage. N Engl J Med. 2022 Oct 27;387(17):1589-1596. doi: 10.1056/NEJMra2201449. No abstract available.

Reference Type: RESULT

PMID: 36300975 (View on PubMed)

Gross BA, Jankowitz BT, Friedlander RM. Cerebral Intraparenchymal Hemorrhage: A Review. JAMA. 2019 Apr 2;321(13):1295-1303. doi: 10.1001/jama.2019.2413.

Reference Type: RESULT

PMID: 30938800 (View on PubMed)

Wang WJ, Lu JJ, Wang YJ, Wang CX, Wang YL, Hoff K, Yang ZH, Liu LP, Wang AX, Zhao XQ; China National Stroke Registry (CNSR). Clinical characteristics, management, and functional outcomes in Chinese patients within the first year after intracerebral hemorrhage: analysis from China National Stroke Registry. CNS Neurosci Ther. 2012 Sep;18(9):773-80. doi: 10.1111/j.1755-5949.2012.00367.x.

Reference Type: RESULT

PMID: 22943144 (View on PubMed)

Flower O, Smith M. The acute management of intracerebral hemorrhage. Curr Opin Crit Care. 2011 Apr;17(2):106-14. doi: 10.1097/MCC.0b013e328342f823.

Reference Type: RESULT

PMID: 21169826 (View on PubMed)

Zhao Y, Hua X, Ren X, Ouyang M, Chen C, Li Y, Yin X, Song P, Chen X, Wu S, Song L, Anderson CS. Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality. Int J Stroke. 2023 Mar;18(3):259-267. doi: 10.1177/17474930221135983. Epub 2022 Nov 16.

Reference Type: RESULT

PMID: 36274585 (View on PubMed)

Ma Q, Li R, Wang L, Yin P, Wang Y, Yan C, Ren Y, Qian Z, Vaughn MG, McMillin SE, Hay SI, Naghavi M, Cai M, Wang C, Zhang Z, Zhou M, Lin H, Yang Y. Temporal trend and attributable risk factors of stroke burden in China, 1990-2019: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2021 Dec;6(12):e897-e906. doi: 10.1016/S2468-2667(21)00228-0.

Reference Type: RESULT

PMID: 34838196 (View on PubMed)

GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. Epub 2021 Sep 3.

Reference Type: RESULT

PMID: 34487721 (View on PubMed)

Other Identifiers

MISTICH

Identifier Type: -

Identifier Source: org_study_id