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

Capital Medical University

Status and phase: Completed; Phase 3

Conditions: Ischemic Stroke, Acute

Treatments: Drug: Placebo capsules of Minocycline hydrochloride capsules; Drug: Minocycline hydrochloride capsule

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05836740

KY2023-007-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,724 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,724 participants in 2 patient groups, including a placebo group

Minocycline treatment group

Active Comparator group

Description:

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)

Treatment:

Drug: Minocycline hydrochloride capsule

Minocycline placebo-control group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo capsules of Minocycline hydrochloride capsules