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

Primary Purpose

Ischemic Stroke, Acute

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Minocycline hydrochloride capsule
Placebo capsules of Minocycline hydrochloride capsules
Sponsored by
Beijing Tiantan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke, Acute focused on measuring Ischemic Stroke, Minocycline

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria: 18≤Age≤80 years old; Patients with acute ischemic stroke confirmed by CT or MRI within 72 hours of onset; 4≤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. Exclusion criteria: 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. 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.

Sites / Locations

  • Beijing Tiantan HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Minocycline treatment group

Minocycline placebo-control group

Arm 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)

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.

Outcomes

Primary Outcome Measures

mRS score 0-1
Modified Rankin Scale score.

Secondary Outcome Measures

mRS score.
Modified Rankin Scale score.
Changes in NIHSS score compared with baseline score.
NIHSS score
Changes in hs-CRP level compared with baseline level.
hs-CRP was examined to evaluate the level of systematic inflammation
Early neurological deterioration.
Early neurological deterioration was defined as any new neurological symptoms or signs that occur within several hours or days of onset, as well as the progression of existing neurological deficit symptoms or signs.
Recurrent stroke.
Recurrent stroke includes recurrent ischemic stroke and recurrent hemorrhagic stroke.
Recurrent ischemic stroke.
The condition of recurrent ischemic stroke.
Combined vascular events.
Combined vascular events referred to stroke, myocardial infarction, and vascular death.
Quality of life (EQ-5D) score.
Scores of EuroQol (Quality of life) -5 Dimensions.

Full Information

First Posted
April 19, 2023
Last Updated
August 3, 2023
Sponsor
Beijing Tiantan Hospital
Collaborators
NeuroDawn Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05836740
Brief Title
Efficacy and Safety of Minocycline in Patients With Moderate to Severe Acute Ischemic Stroke
Acronym
EMPHASIS
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2023 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Tiantan Hospital
Collaborators
NeuroDawn Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Acute
Keywords
Ischemic Stroke, Minocycline

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
1672 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Minocycline treatment group
Arm Type
Active Comparator
Arm 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)
Arm Title
Minocycline placebo-control group
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Minocycline hydrochloride capsule
Intervention Description
50 mg per capsule, containing 50mg of Minocycline Hydrochloride.
Intervention Type
Drug
Intervention Name(s)
Placebo capsules of Minocycline hydrochloride capsules
Intervention Description
50 mg per capsule, containing 0mg of Minocycline Hydrochloride.
Primary Outcome Measure Information:
Title
mRS score 0-1
Description
Modified Rankin Scale score.
Time Frame
At 90±7 days after randomization.
Secondary Outcome Measure Information:
Title
mRS score.
Description
Modified Rankin Scale score.
Time Frame
At 90±7 days after randomization.
Title
Changes in NIHSS score compared with baseline score.
Description
NIHSS score
Time Frame
At 24±1 hours and 6±1 days after randomization.
Title
Changes in hs-CRP level compared with baseline level.
Description
hs-CRP was examined to evaluate the level of systematic inflammation
Time Frame
At 6±1 days after randomization.
Title
Early neurological deterioration.
Description
Early neurological deterioration was defined as any new neurological symptoms or signs that occur within several hours or days of onset, as well as the progression of existing neurological deficit symptoms or signs.
Time Frame
At 24±2 hours and 6±1 days after randomization.
Title
Recurrent stroke.
Description
Recurrent stroke includes recurrent ischemic stroke and recurrent hemorrhagic stroke.
Time Frame
At 90±7 days after randomization.
Title
Recurrent ischemic stroke.
Description
The condition of recurrent ischemic stroke.
Time Frame
At 90±7 days after randomization.
Title
Combined vascular events.
Description
Combined vascular events referred to stroke, myocardial infarction, and vascular death.
Time Frame
At 90±7 days after randomization.
Title
Quality of life (EQ-5D) score.
Description
Scores of EuroQol (Quality of life) -5 Dimensions.
Time Frame
At 90±7 days after randomization.
Other Pre-specified Outcome Measures:
Title
Changes in the levels of venous neuroinflammation indicators and thrombotic inflammation indicators compared with baseline levels.
Description
Venous neuroinflammation indicators (NF-L, S100B, copeptin, etc.) and thrombotic inflammation indicators (plasma sGPVI, sADAMTS 13, sCD40L, sP-selectin, etc.)
Time Frame
At 24±2 hours and 6±1 days after randomization.
Title
Cerebral hemodynamic function.
Description
Cerebral hemodynamics was reflected by cerebral autoregulation function, and autonomic nervous function was evaluated by heart rate variability.
Time Frame
At 6±1 days and 90±7 days after randomization.
Title
Changes in the levels of venous intestinal flora metabolites compared with baseline levels
Description
plasma TMAO and its precursors, etc.
Time Frame
At 6±1 days after randomization.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 18≤Age≤80 years old; Patients with acute ischemic stroke confirmed by CT or MRI within 72 hours of onset; 4≤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. Exclusion criteria: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yilong Wang, PhD+MD
Phone
0086-010-67092222
Ext
0
Email
yilong528@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yilong Wang, PhD+MD
Organizational Affiliation
Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Tiantan Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
yilong Wang, MD, PhD

12. IPD Sharing Statement

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

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