Efficacy and Safety of Minocycline in Patients With Moderate to Severe Acute Ischemic Stroke

NCT05836740 | Completed Phase 3 DMC

• 1 other identifier: KY2023-007-01
• Study Type: interventional
• Target: 1,724
• Locations: 1 country
• Sites: 58

Brief Summary

The aim of this study was to evaluate the efficacy and safety of Minocycline versus placebo in the treatment of patients with moderate to severe acute ischemic stroke.

Conditions

Ischemic Stroke, Acute

Keywords

Ischemic Stroke; Minocycline

Outcome Measures

Primary Outcomes (1)

• mRS score 0-1

  Modified Rankin Scale score.

  At 90±7 days after randomization.

Secondary Outcomes (8)

• mRS score.

  At 90±7 days after randomization.

• Changes in NIHSS score compared with baseline score.

  At 24±1 hours and 6±1 days after randomization.

• Changes in hs-CRP level compared with baseline level.

  At 6±1 days after randomization.

• Early neurological deterioration.

  At 24±2 hours and 6±1 days after randomization.

• Recurrent stroke.

  At 90±7 days after randomization.

Other Outcomes (3)

• Changes in the levels of venous neuroinflammation indicators and thrombotic inflammation indicators compared with baseline levels.

  At 24±2 hours and 6±1 days after randomization.

• Cerebral hemodynamic function.

  At 6±1 days and 90±7 days after randomization.

• Changes in the levels of venous intestinal flora metabolites compared with baseline levels

  At 6±1 days after randomization.

Study Arms (2)

Minocycline treatment group

ACTIVE COMPARATOR

Minocycline Hydrochloride Capsules (50 mg per capsule) The first dose should be given immediately after randomization (within 30 minutes); 200mg (4 capsules) for the first dose; Subsequently, 100mg (2 capsules) will be administered once every 12 hours, a total of 9 times (lasting 4.5 days; the subject with dysphagia will be administrated through a nasal feeding tube)

Drug: Minocycline hydrochloride capsule

Minocycline placebo-control group

PLACEBO COMPARATOR

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.

Drug: Placebo capsules of Minocycline hydrochloride capsules

Interventions

Minocycline hydrochloride capsule DRUG

50 mg per capsule, containing 50mg of Minocycline Hydrochloride.

Minocycline treatment group

Placebo capsules of Minocycline hydrochloride capsules DRUG

50 mg per capsule, containing 0mg of Minocycline Hydrochloride.

Minocycline placebo-control 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≤80 years old;
• Patients with acute ischemic stroke confirmed by CT or MRI within 72 hours of onset;
• ≤NIHSS≤25, and Ia≤1;
• First stroke or mRS 0-1 before the onset of current stroke;
• Patients or his/her legal representatives are able to understand and sign the informed consent.

You may not qualify if:

• History of pseudomembranous colitis or antibiotic-related colitis.
• Allergic to tetracycline antibiotics or any component of the investigational drug.
• Known to be resistant to other tetracyclines.
• Took tetracycline antibiotics within previous one week.
• Known community-acquired bacterial infection, such as pneumonia or urinary tract infection.
• History of intracranial hemorrhagic diseases within previous 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc.
• Intracranial tumors, vascular malformations and other intracranial space-occupying lesions.
• Rare or unknown etiology of LVO, such as dissection and vasculitis.
• Severe hepatic insufficiency, renal insufficiency or receiving dialysis before randomization for various reasons (Severe hepatic insufficiency was defined as ALT \>3 times the upper limit of normal value or AST \>3 times the upper limit of normal value; Severe renal insufficiency was defined as creatinine \> 3.0 mg/dl \[265.2 μmol/L\] or glomerular filtration rate\<30 ml/min/1.73m2).
• Bleeding tendency (including but not limited to): platelet count \<100×109/L; Administration of oral warfarin and INR\>2; Administration of heparin within previous 48 hours and APTT≥35s; Hereditary bleeding disorders, such as hemophilia.
• Received any of the following treatments within previous 3 months: systemic retinoic acid, androgen/antiandrogen therapy (e.g., anabolic steroids, andiolactone).
• History of intracranial or spinal surgery within previous 3 months; History of therapeutical surgery or major physical trauma within previous 1 month.
• Women of childbearing age who do not use effective contraception and have no negative pregnancy test records; Women during lactation and pregnancy.
• Life expectancy of less than 6 months due to advanced stage of comorbidity.
• Participated in other interventional clinical trials within previous 3 months.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Neurodawn Pharmaceutical Co., Ltd.: collaborator

Study Sites (58)

The Eighth Medical Center of PLA General Hospital

Beijing, Beijing Municipality, 100000, China

Location

Beijing Shunyi Hospital

Beijing, Beijing Municipality, 101300, China

Location

Chongqing Donghua Hospital

Chongqing, Chongqing Municipality, 400032, China

Location

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, 404000, China

Location

Shenzhen Hospital, Southern Medical University

Shenzhen, Guangdong, 518000, China

Location

Shenzhen Second People's Hospital

Shenzhen, Guangdong, 518000, China

Location

The Second Nanning People's Hospital

Nanning, Guangxi, 530031, China

Location

The Sixth People's Hospital of Hengshui

Hengshui, Hebei, 053000, China

Location

North China University of Science and Technology Affiliated Hospital

Tangshan, Hebei, 063000, China

Location

Dengzhou People's Hospital

Dengzhou, Henan, 474100, China

Location

Xiuwu People's Hospital

Jiaozuo, Henan, 454350, China

Location

Jiyuan Chinese Medical Hospital

Jiyuan, Henan, 459000, China

Location

Luoyang Central Hospital

Luoyang, Henan, 471000, China

Location

Mengjin People's Hospital

Luoyang, Henan, 471100, China

Location

Luoning People's Hospital

Luoyang, Henan, 471700, China

Location

Mengzhou People's Hospital

Mengzhou, Henan, 454750, China

Location

Nanle Zhongxing Hospital

Puyang, Henan, 457400, China

Location

Sui Chinese Medical Hospital

Shangqiu, Henan, 476900, China

Location

Xingyang People's Hospital

Zhengzhou, Henan, 450100, China

Location

Biyang People's Hospital

Zhumadian, Henan, 463000, China

Location

Pingyu People's Hospital

Zhumadian, Henan, 463400, China

Location

Wuhan No.1 Hospital

Wuhan, Hubei, 430000, China

Location

Shimen People's Hospital

Changde, Hunan, 415300, China

Location

Xiangya Hospital, Central South University

Changsha, Hunan, 410000, China

Location

The First People's Hospital of Chenzhou/The First Affiliated Hospital of Xiangnan University

Chenzhou, Hunan, 423000, China

Location

Hengyang Central Hospital

Hengyang, Hunan, 421002, China

Location

Baotou Central Hospital

Baotou, Inner Mongolia, 014030, China

Location

Changzhou Wujin Traditional Chinese Medicine Hospital

Changzhou, Jiangsu, 213100, China

Location

Rudong People's Hospital

Nantong, Jiangsu, 226400, China

Location

The Fourth Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

Location

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

Location

Jiujiang University Affiliated Hospital

Jiujiang, Jiangxi, 332000, China

Location

China-Japan Union Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

Benxi Central Hospital

Benxi, Liaoning, 117000, China

Location

The First Affiliated Hospital of Jinzhou Medical University

Jinzhou, Liaoning, 121000, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750000, China

Location

Affiliated Hospital of Jining Medical University

Jining, Shandong, 272000, China

Location

Liaocheng Central Hospital

Liaocheng, Shandong, 252000, China

Location

The Third People's Hospital of Liaocheng

Liaocheng, Shandong, 252000, China

Location

Guanxian People's Hospital

Liaocheng, Shandong, 252500, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266000, China

Location

Weihai Wendeng District People's Hospital

Weihai, Shandong, 264400, China

Location

Zibo Central Hospital

Zibo, Shandong, 255000, China

Location

Shanghai Pudong New Area Gongli Hospital

Shanghai, Shanghai Municipality, 200135, China

Location

Xi'an International Medical Center Hospital

Xi'an, Shannxi, 710000, China

Location

Yuci District People's Hospital

Jinzhong, Shanxi, 030600, China

Location

Linfen Central Hospital

Linfen, Shanxi, 041000, China

Location

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610000, China

Location

Tianjin Xiqing Hospital

Tianjin, Tianjin Municipality, 130000, China

Location

Tianjin Huanhu Hospital

Tianjin, Tianjin Municipality, 300000, China

Location

Xinjiang Production and Construction Corps 13 Division Red Star Hospital

Hami, Xinjiang, 839000, China

Location

Xinjiang Production&Construction Corps Hospital

Ürümqi, Xinjiang, 830002, China

Location

Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

Location

Beijing Tiantan Hospital

Beijing, China

Location

Ningjin People's Hospital

Dezhou, 253400, China

Location

Zouping City People's Hospital

Jining, 256200, China

Location

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MeSH Terms

Conditions

Ischemic Stroke; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Yilong Wang, PhD+MD

  Beijing Tiantan Hospital, Capital Medical University, Beijing, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Minocycline drug used in the study is indistinguishable from the Minocycline placebo (the shape, color, and appearance are identical). In addition, to ensure the blind method, the drug packaging and batch numbers of the two groups are identical, and the packaging batch numbers are uniformly marked. During the implementation of the study, except for the authorized personnel of the company's supply chain, research management department, and subject security department, members of each research execution group, research center personnel, and CRO data processing personnel cannot view the randomization scheme. The blind method was also used to evaluate the outcome. The participants were randomly divided into groups and blinded to the members of the adjudication committee.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Model Details: This trial was a prospective, randomized, multicenter, double-blind, placebo-controlled parallel trial. Participants were randomly assigned according to the ratio of the experimental group: control group =1:1.

Study Record Dates

• First Submitted: April 19, 2023
• First Posted: May 1, 2023
• Study Start: May 19, 2023
• Primary Completion: May 20, 2024
• Study Completion: August 15, 2024
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (58)