Ischaemic StrokePhase 3EMPHASIS-2NCT07526987
Efficacy and Safety of Minocycline in Patients With Acute Ischaemic Stroke Receiving Intravenous Thrombolysis
A Phase 3 study testing Minocycline Hydrochloride Capsule (50 mg per capsule) in people with Ischaemic Stroke, run by Beijing Tiantan Hospital at 3 sites in China.
Trial summary
The aim of this study is to assess the efficacy and safety of minocycline in improving functional outcome among patients with acute ischaemic stroke receiving intravenous thrombolysis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischaemic Stroke
- What is being tested?
- Minocycline Hydrochloride Capsule (50 mg per capsule)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 934 participants
- Where
- 3 sitesChina
- Study dates
- 5 Jun 2026to 31 Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 80 years;
- Patients with acute ischaemic stroke confirmed by CT or MRI;
- Having received or planning to receive intravenous thrombolysis within 4.5 hours of onset or within an extended window of 4.5-24 hours based on guideline recommendations (The intravenous thrombolytic drugs include: alteplase, tenecteplase, reteplase or recombinant human prourokinase);
- The study drug can be applied before intravenous thrombolysis or within 2 hours after the initiation of intravenous thrombolysis;
- 6≤NIHSS≤25, and Ia≤1;
- Signed informed consent.
Who cannot join
- mRS score ≥ 2 prior to onset of the current stroke;
- History of pseudomembranous colitis or antibiotic-associated colitis;
- Known allergy or intolerance to tetracycline antibiotics or any component of minocycline;
- Known resistance to other tetracyclines;
- Use of tetracycline antibiotics within the past 7 days;
- Presence of a known community-acquired bacterial infection (e.g., pneumonia, urinary tract infection) or any other concurrent infection requiring antibiotic treatment;
Show all 16Show fewer
- History of intracranial hemorrhagic disease within the past 3 months, for example, parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural or epidural hematoma.
- Malformation, tumor, abscess, or other major non-ischaemic brain diseases (e.g., multiple sclerosis, other intracranial space-occupying lesions) on baseline cranial CT or MRI;
- Rare or unknown etiology of large vessel occlusion (e.g., arterial dissection, vasculitis);
- History of systemic lupus erythematosus;
- Known severe hepatic insufficiency (ALT or AST > 3 times of the upper limit of normal), severe renal insufficiency (creatinine > 3.0 mg/dL [265.2 μmol/L], estimated glomerular filtration rate <30 mL/min/1.73m², or have received dialysis before randomization);
- Use of tretinoin, androgen or antiandrogen treatment (e.g., anabolic steroids, spironolactone) within the past 3 months;
- Pregnant, breastfeeding, or of childbearing potential who are unwilling to use effective contraception throughout the study;
- Presence of a severe non-cardio-cerebrovascular disease with a life expectancy of less than 6 months;
- Participation in any other clinical trial within the past 30 days;
- Any other condition that is not suitable for participating in this clinical trial, such as inability to understand or follow the study procedures due to physical, cognitive, emotional, or mental disorders.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Not yet recruiting
Beijing Tiantan Hospital
Beijing, 100070
Anxin Wang, PhD, 8601059976951, wanganxin@bjttyy.com
Yilong Wang, MD, PhD
- Recruiting
Liaocheng Third People's Hospital
Liaocheng, Shandong, 252000
Ke Diao, 8613869550081, 13869550081@163.com
- Recruiting
Guanxian People's Hospital
Liaocheng, Shandong, 252500
Tao Xing, 8618663027003, zzy224@163.com
About this study
Official title: Efficacy and Safety of Minocycline in Patients With Acute Ischaemic Stroke Receiving Intravenous Thrombolysis (EMPHASIS-2): A Multicenter, Randomized, Double-blind, Placebo-parallel Controlled Trial
The aim of this study is to assess the efficacy and safety of minocycline in improving functional outcome among patients with acute ischaemic stroke receiving intravenous thrombolysis.
Read the detailed description
Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess a wide range of cytoprotective properties independent of its antibacterial activity, which have translated into promising therapeutic potential for acute ischaemic stroke. Specifically, the drug improves post-stroke outcomes by targeting post-ischaemic neuroinflammation through multiple mechanisms. Early-phase clinical trials first indicated that minocycline treatment, initiated within 6-24 hours after stroke, could improve functional outcomes for up to 90 days. This promise was recently substantiated by the EMPHASIS trial, which demonstrated that minocycline administered within 72 hours of ischaemic stroke onset significantly improved 90-day functional outcomes compared to placebo, with a favorable safety profile. Furthermore, preclinical research has shown that combining minocycline with t-PA can improve thrombolytic efficacy, extend the therapeutic time window, and reduce the risk of hemorrhagic transformation. Hence, this study-a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial-aims to evaluate whether minocycline improves functional outcomes in patients with acute ischaemic stroke undergoing intravenous thrombolysis.
Patients aged 18 to 80 years with a newly diagnosed ischaemic stroke (NIHSS score of 6-25 and Ia ≤1), who have received/are planned to receive intravenous thrombolysis within 4.5 hours of onset or within an extended window of 4.5-24 hours based on guideline recommendations, and can be treated with the study drug either before thrombolysis or within 2 hours after its initiation, will be enrolled. Eligible patients will be randomly assigned in a 1:1 ratio to receive minocycline or placebo.
The primary efficacy outcome is an excellent functional outcome (a mRS score of 0 or 1) at 90 days. The secondary efficacy outcomes include a good functional outcome (a mRS score of 0 to 2) at 90 days, the ordinal distribution of mRS score at 90 days, quality of life (EQ-5D) score at 90 days, a Barthel Index score of at least 95 at 90 days, the change from baseline in the NIHSS score at 6 days, and major neurologic improvement at 6 days (defined as a decrease from baseline of ≥ 4 points on the NIHSS, or an NIHSS score of ≤1). Safety outcomes include diarrhoea, enteritis, and constipation within 6 days, symptomatic intracranial hemorrhage within 6 days, any bleeding events, adverse events or serious adverse events within 90 days.
Randomized participants will be interviewed at screening/baseline period, 6 days, 30±3 days, 60±5 days, and 90±7 days after randomization.
- Conditions
- Ischaemic Stroke
- Being tested
- Minocycline Hydrochloride Capsule (50 mg per capsule), Placebo of Minocycline Hydrochloride Capsule (50 mg per capsule, containing 0 mg of minocycline)
- Keywords
- Ischaemic stroke, Intravenous thrombolysis, Minocycline, Randomized Controlled Trial, Functional outcome
- Medical subject headings
- Ischemic Stroke, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Minocycline Hydrochloride Capsule (50 mg per capsule)Drug
A loading dose of 200 mg will be administered before intravenous thrombolysis or within 2 hours after the initiation of intravenous thrombolysis, followed by a maintenance dose of 100 mg every 12 hours for the subsequent 4 days.
A total of 9 times will be administered over a period of 4.5 days. Minocycline hydrochloride capsules will be administered orally or via a nasogastric feeding tube if the participant has dysphagia.
Placebo of Minocycline Hydrochloride Capsule (50 mg per capsule, containing 0 mg of minocycline)Drug
A loading dose of 200 mg will be administered before intravenous thrombolysis or within 2 hours after the initiation of intravenous thrombolysis, followed by a maintenance dose of 100 mg every 12 hours for the subsequent 4 days.
A total of 9 times will be administered over a period of 4.5 days. Placebo capsules will be administered orally or via a nasogastric feeding tube if the participant has dysphagia.
| Study group | Role | What they receive |
|---|---|---|
| Minocycline Therapy | Experimental | This group will receive minocycline hydrochloride capsules. Receives: Drug: Minocycline Hydrochloride Capsule (50 mg per capsule) |
| Placebo | Placebo comparator | This group will receive placebo of minocycline hydrochloride capsules. Receives: Drug: Placebo of Minocycline Hydrochloride Capsule (50 mg per capsule, containing 0 mg of minocycline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Excellent functional outcome (mRS of 0-1)
Defined as an modified Rankin Scale (mRS) score of 0 or 1. The mRS scores range from 0 (no symptoms) to 5 (severe disability) and 6 (death).
Measured: 90 days
Secondary outcomes (11)
Good functional outcome (mRS of 0-2)
Defined as an modified Rankin Scale (mRS) score of 0 or 2. The mRS scores range from 0 (no symptoms) to 5 (severe disability) and 6 (death).
Measured: 90 days
Distribution of mRS score
The ordinal distribution of mRS score of 0 to 6 points
Measured: 90 days
Quality of life score (EQ-5D scale)
The European Quality of Life 5-Dimension (EQ-5D）questionnaire for measuring generic health status. The 5-level EQ-5D version (EQ-5D-5L) comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The sum score on each of the five dimensions ranges from 5 (all domains have level 1) to 25 (all domains have level 5), with higher scores indicating worse health-related quality of life.
Measured: 90 days
Barthel Index score ≥ 95
The Barthel index score ranges from 0 to 100, with higher scores indicating better independent function.
Measured: 90 days
Changes from baseline of National Institutes of Health Stroke Scale (NIHSS) score
Defined as the difference between the 6-day NIHSS score and the baseline NIHSS score. The National Institutes of Health Stroke Scale (NIHSS) score ranges from 0 to 42, with higher scores indicating more severe neurological deficit.
Measured: 6 days
Major neurologic improvement
Defined as NIHSS score ≤ 1 point at 6 days or an improvement of ≥ 4 points compared to the baseline NIHSS score. The National Institutes of Health Stroke Scale (NIHSS) score ranges from 0 to 42, with higher scores indicating more severe neurological deficit.
Measured: 6 days
The proportion of participants with diarrhoea, enteritis, and constipation
Measured: 6 days
The proportion of participants with symptomatic intracranial hemorrhage
Defined by the European Cooperative Acute Stroke Study III (ECASS III)
Measured: 6 days
The proportion of participants with any bleeding events
Defined by the Global Utilisation of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Criteria (GUSTO)
Measured: 90 days
The proportion of participants with adverse events
Measured: 90 days
The proportion of participants with serious adverse events
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2026
- Study start5 Jun 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischaemic StrokeStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Eligible patients will be randomly assigned in a 1:1 ratio to receive minocycline or placebo. Treatment will be initiated before intravenous thrombolysis or within 2 hours after its initiation, and last for 4.5 days. The primary outcome is an excellent functional outcome (a mRS score of 0 or 1) at 90 days.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 934 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, yilong Wang, Beijing Tiantan Hospital
- Investigators
- Yilong Wang, MD, PhD, Principal investigator, Beijing Tiantan HospitalAnxin Wang, PhD, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07526987
- Sponsor's protocol ID
- 2025-B14
- Acronym
- EMPHASIS-2
- Status last verified
- Jun 2026
- First submitted
- 8 Apr 2026
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Minocycline in Patients With Acute Ischaemic Stroke Receiving Intravenous Thrombolysis (EMPHASIS-2): A Multicenter, Randomized, Double-blind, Placebo-parallel Controlled Trial
- ClinicalTrials.gov ID
- NCT07526987
- Acronym / sponsor ID
- EMPHASIS-2 / 2025-B14
- Conditions
- Ischaemic Stroke
- Keywords
- Ischaemic stroke, Intravenous thrombolysis, Minocycline, Randomized Controlled Trial, Functional outcome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 934 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 5 Jun 2026 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 14 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the efficacy and safety of minocycline in improving functional outcome among patients with acute ischaemic stroke receiving intravenous thrombolysis.
Detailed description
Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess a wide range of cytoprotective properties independent of its antibacterial activity, which have translated into promising therapeutic potential for acute ischaemic stroke. Specifically, the drug improves post-stroke outcomes by targeting post-ischaemic neuroinflammation through multiple mechanisms. Early-phase clinical trials first indicated that minocycline treatment, initiated within 6-24 hours after stroke, could improve functional outcomes for up to 90 days. This promise was recently substantiated by the EMPHASIS trial, which demonstrated that minocycline administered within 72 hours of ischaemic stroke onset significantly improved 90-day functional outcomes compared to placebo, with a favorable safety profile. Furthermore, preclinical research has shown that combining minocycline with t-PA can improve thrombolytic efficacy, extend the therapeutic time window, and reduce the risk of hemorrhagic transformation. Hence, this study-a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial-aims to evaluate whether minocycline improves functional outcomes in patients with acute ischaemic stroke undergoing intravenous thrombolysis.
Patients aged 18 to 80 years with a newly diagnosed ischaemic stroke (NIHSS score of 6-25 and Ia ≤1), who have received/are planned to receive intravenous thrombolysis within 4.5 hours of onset or within an extended window of 4.5-24 hours based on guideline recommendations, and can be treated with the study drug either before thrombolysis or within 2 hours after its initiation, will be enrolled. Eligible patients will be randomly assigned in a 1:1 ratio to receive minocycline or placebo.
The primary efficacy outcome is an excellent functional outcome (a mRS score of 0 or 1) at 90 days. The secondary efficacy outcomes include a good functional outcome (a mRS score of 0 to 2) at 90 days, the ordinal distribution of mRS score at 90 days, quality of life (EQ-5D) score at 90 days, a Barthel Index score of at least 95 at 90 days, the change from baseline in the NIHSS score at 6 days, and major neurologic improvement at 6 days (defined as a decrease from baseline of ≥ 4 points on the NIHSS, or an NIHSS score of ≤1). Safety outcomes include diarrhoea, enteritis, and constipation within 6 days, symptomatic intracranial hemorrhage within 6 days, any bleeding events, adverse events or serious adverse events within 90 days.
Randomized participants will be interviewed at screening/baseline period, 6 days, 30±3 days, 60±5 days, and 90±7 days after randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Eligible patients will be randomly assigned in a 1:1 ratio to receive minocycline or placebo. Treatment will be initiated before intravenous thrombolysis or within 2 hours after its initiation, and last for 4.5 days. The primary outcome is an excellent functional outcome (a mRS score of 0 or 1) at 90 days.
| Arm | Type | Receives |
|---|---|---|
| Minocycline Therapy | Experimental | Drug: Minocycline Hydrochloride Capsule (50 mg per capsule)This group will receive minocycline hydrochloride capsules. |
| Placebo | Placebo comparator | Drug: Placebo of Minocycline Hydrochloride Capsule (50 mg per capsule, containing 0 mg of minocycline)This group will receive placebo of minocycline hydrochloride capsules. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age between 18 and 80 years;
- Patients with acute ischaemic stroke confirmed by CT or MRI;
- Having received or planning to receive intravenous thrombolysis within 4.5 hours of onset or within an extended window of 4.5-24 hours based on guideline recommendations (The intravenous thrombolytic drugs include: alteplase, tenecteplase, reteplase or recombinant human prourokinase);
- The study drug can be applied before intravenous thrombolysis or within 2 hours after the initiation of intravenous thrombolysis;
- 6≤NIHSS≤25, and Ia≤1;
Key exclusion criteria (16 listed)
- mRS score ≥ 2 prior to onset of the current stroke;
- History of pseudomembranous colitis or antibiotic-associated colitis;
- Known allergy or intolerance to tetracycline antibiotics or any component of minocycline;
- Known resistance to other tetracyclines;
- Use of tetracycline antibiotics within the past 7 days;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Minocycline Hydrochloride Capsule (50 mg per capsule)A loading dose of 200 mg will be administered before intravenous thrombolysis or within 2 hours after the initiation of intravenous thrombolysis, followed by a maintenance dose of 100 mg every 12 hours for the subsequent 4 days. A total of 9 times will be administered over a period of 4.5 days. Minocycline hydrochloride capsules will be administered orally or via a nasogastric feeding tube if the participant has dysphagia. | Drug | Minocycline Therapy |
| Placebo of Minocycline Hydrochloride Capsule (50 mg per capsule, containing 0 mg of minocycline)A loading dose of 200 mg will be administered before intravenous thrombolysis or within 2 hours after the initiation of intravenous thrombolysis, followed by a maintenance dose of 100 mg every 12 hours for the subsequent 4 days. A total of 9 times will be administered over a period of 4.5 days. Placebo capsules will be administered orally or via a nasogastric feeding tube if the participant has dysphagia. | Drug | Placebo |
Primary outcome
Excellent functional outcome (mRS of 0-1)
Time frame: 90 days
Defined as an modified Rankin Scale (mRS) score of 0 or 1. The mRS scores range from 0 (no symptoms) to 5 (severe disability) and 6 (death).
11 secondary outcomes
Good functional outcome (mRS of 0-2)
Time frame: 90 days
Distribution of mRS score
Time frame: 90 days
Quality of life score (EQ-5D scale)
Time frame: 90 days
Barthel Index score ≥ 95
Time frame: 90 days
Changes from baseline of National Institutes of Health Stroke Scale (NIHSS) score
Time frame: 6 days
Major neurologic improvement
Time frame: 6 days
The proportion of participants with diarrhoea, enteritis, and constipation
Time frame: 6 days
The proportion of participants with symptomatic intracranial hemorrhage
Time frame: 6 days
The proportion of participants with any bleeding events
Time frame: 90 days
The proportion of participants with adverse events
Time frame: 90 days
The proportion of participants with serious adverse events
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yilong Wang, MD, PhD principal investigator
Beijing Tiantan Hospital
Anxin Wang, PhD principal investigator
Beijing Tiantan Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Minocycline Hydrochloride Capsule (50 mg per capsule) in people with Ischaemic Stroke, run by Beijing Tiantan Hospital at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anxin Wang, PhD (8601059976951, wanganxin@bjttyy.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Excellent functional outcome (mRS of 0-1) (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.