Clinical trial NCT05836740: Efficacy and Safety of Minocycline in Patients With Moderate to Severe Acute Ischemic Stroke
Official title: Efficacy and Safety of Minocycline in Patients With Moderate to Severe Acute Ischemic Stroke: A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Phase III Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke, Acute
Keywords: Ischemic Stroke
Minocycline
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Neurodawn Pharmaceutical Co., Ltd.
First posted: 2023-05-01
Enrollment: 1724
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: The aim of this study was to evaluate the efficacy and safety of 4.5-days Minocycline versus placebo in patients with moderate to severe acute ischemic stroke within 72 hours of onset. In addition, we will explore the effect of Minocycline versus placebo on indicators of venous neuroinflammation and thrombo-inflammation at different time points in patients with moderate to severe acute ischemic stroke within 72 hours of onset.

The primary objective is to evaluate the effect of Minocycline in improving the level of mRS score to 0-1 in patients with moderate to severe acute ischemic stroke within 72 hours of onset.

The trial was divided into three phases: screening/baseline period, treatment period, and follow-up period. The visit schedule is as follows: Randomized participants were interviewed at screening/baseline period, 24±2 hours, 6±1 days, 90±7 days after randomization, and when events occurred.

Eligibility criteria: Inclusion criteria:

1. 18≤Age≤80 years old;
2. Patients with acute ischemic stroke confirmed by CT or MRI within 72 hours of onset;
3. 4≤NIHSS≤25, and Ia≤1;
4. First stroke or mRS 0-1 before the onset of current stroke;
5. Patients or his/her legal representatives are able to understand and sign the informed consent.

Exclusion criteria:

1. History of pseudomembranous colitis or antibiotic-related colitis.
2. Allergic to tetracycline antibiotics or any component of the investigational drug.
3. Known to be resistant to other tetracyclines.
4. Took tetracycline antibiotics within previous one week.
5. Known community-acquired bacterial infection, such as pneumonia or urinary tract infection.
6. History of intracranial hemorrhagic diseases within previous 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/external hematoma, etc.
7. Intracranial tumors, vascular malformations and other intracranial space-occupying lesions.
8. Rare or unknown etiology of LVO, such as dissection and vasculitis.
9. 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).
10. 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.
11. Received any of the following treatments within previous 3 months: systemic retinoic acid, androgen/antiandrogen therapy (e.g., anabolic steroids, andiolactone).
12. History of intracranial or spinal surgery within previous 3 months; History of therapeutical surgery or major physical trauma within previous 1 month.
13. Women of childbearing age who do not use effective contraception and have no negative pregnancy test records; Women during lactation and pregnancy.
14. Life expectancy of less than 6 months due to advanced stage of comorbidity.
15. Participated in other interventional clinical trials within previous 3 months.
16. 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.

Primary outcomes:
measure: mRS score 0-1
timeFrame: At 90±7 days after randomization.
Secondary outcomes:
measure: mRS score.
timeFrame: At 90±7 days after randomization.
measure: Changes in NIHSS score compared with baseline score.
timeFrame: At 24±1 hours and 6±1 days after randomization.
measure: Changes in hs-CRP level compared with baseline level.
timeFrame: At 6±1 days after randomization.
measure: Early neurological deterioration.
timeFrame: At 24±2 hours and 6±1 days after randomization.
measure: Recurrent stroke.
timeFrame: At 90±7 days after randomization.
measure: Recurrent ischemic stroke.
timeFrame: At 90±7 days after randomization.
measure: Combined vascular events.
timeFrame: At 90±7 days after randomization.
measure: Quality of life (EQ-5D) score.
timeFrame: At 90±7 days after randomization.
Other outcomes:
measure: Changes in the levels of venous neuroinflammation indicators and thrombotic inflammation indicators compared with baseline levels.
timeFrame: At 24±2 hours and 6±1 days after randomization.
measure: Cerebral hemodynamic function.
timeFrame: At 6±1 days and 90±7 days after randomization.
measure: Changes in the levels of venous intestinal flora metabolites compared with baseline levels
timeFrame: At 6±1 days after randomization.
Locations:
city: Beijing
country: China
facility: The Eighth Medical Center of PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shunyi Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Donghua Hospital
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Shenzhen
country: China
facility: Shenzhen Hospital, Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The Second Nanning People's Hospital
state: Guangxi
city: Hengshui
country: China
facility: The Sixth People's Hospital of Hengshui
state: Hebei
city: Tangshan
country: China
facility: North China University of Science and Technology Affiliated Hospital
state: Hebei
city: Dengzhou
country: China
facility: Dengzhou People's Hospital
state: Henan
city: Jiaozuo
country: China
facility: Xiuwu People's Hospital
state: Henan
city: Jiyuan
country: China
facility: Jiyuan Chinese Medical Hospital
state: Henan
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Luoyang
country: China
facility: Mengjin People's Hospital
state: Henan
city: Luoyang
country: China
facility: Luoning People's Hospital
state: Henan
city: Mengzhou
country: China
facility: Mengzhou People's Hospital
state: Henan
city: Puyang
country: China
facility: Nanle Zhongxing Hospital
state: Henan
city: Shangqiu
country: China
facility: Sui Chinese Medical Hospital
state: Henan
city: Zhengzhou
country: China
facility: Xingyang People's Hospital
state: Henan
city: Zhumadian
country: China
facility: Biyang People's Hospital
state: Henan
city: Zhumadian
country: China
facility: Pingyu People's Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan No.1 Hospital
state: Hubei
city: Changde
country: China
facility: Shimen People's Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Chenzhou
country: China
facility: The First People's Hospital of Chenzhou/The First Affiliated Hospital of Xiangnan University
state: Hunan
city: Hengyang
country: China
facility: Hengyang Central Hospital
state: Hunan
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia
city: Changzhou
country: China
facility: Changzhou Wujin Traditional Chinese Medicine Hospital
state: Jiangsu
city: Nantong
country: China
facility: Rudong People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Fourth Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Jiujiang
country: China
facility: Jiujiang University Affiliated Hospital
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Benxi
country: China
facility: Benxi Central Hospital
state: Liaoning
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng Central Hospital
state: Shandong
city: Liaocheng
country: China
facility: The Third People's Hospital of Liaocheng
state: Shandong
city: Liaocheng
country: China
facility: Guanxian People's Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Weihai
country: China
facility: Weihai Wendeng District People's Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pudong New Area Gongli Hospital
state: Shanghai
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
state: Shannxi
city: Jinzhong
country: China
facility: Yuci District People's Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Xiqing Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
city: Hami
country: China
facility: Xinjiang Production and Construction Corps 13 Division Red Star Hospital
state: Xinjiang
city: Wulumuqi
country: China
facility: Xinjiang Production&Construction Corps Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Beijing Tiantan Hospital
city: Dezhou
country: China
facility: Ningjin People's Hospital
city: Jining
country: China
facility: Zouping City People's Hospital
Study officials:
affiliation: Beijing Tiantan Hospital, Capital Medical University, Beijing, China
name: Yilong Wang, PhD+MD
role: PRINCIPAL_INVESTIGATOR
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