Acute StrokePhase 4NeuMASTNCT00930020
Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial
A Phase 4 study testing Minocycline (Borymycin) in people with Acute Stroke, run by Singhealth Foundation at 1 site in Singapore.
Trial summary
Background: Stroke is a leading cause of death and chronic serious disability worldwide. Minocycline, a semisynthetic tetracycline, has consistently been shown in recent years to be neuroprotective in animal models of brain ischemia. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Acute Stroke
- What is being tested?
- Minocycline (Borymycin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 139 participants
- Where
- 1 siteSingapore
- Study dates
- Jul 2009to Nov 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Singapore citizens or permanent residents
- Age range between 21 to 80 years
- NIHSS equal or more than 5 but less than 22 at time of admission
- Clinical diagnosis of acute ischemic stroke according to WHO criteria
- Onset of stroke between 3 to 48 hours prior to start of treatment
- Must have a working telephone line
Who cannot join
- Long term residents of Institutions and Nursing homes
- Patients with significant baseline cognitive dysfunction
- Patients with hemorrhagic stroke
- Pre-stroke MRS more than 1
- Evidence of other disease of the CNS (i.e., brain tumor, CNS infections)
- Known allergic response to tetracycline
Show all 14Show fewer
- Acute or Chronic renal failure
- Hepatitis or liver disease
- Pre-existing infectious disease requiring antibiotics
- Receipts of IV rTPA
- Participation in another clinical trial in the preceding 3 months
- Unable or unwilling to provide inform consent
- Unwilling to return for frequent clinic visits
- Geographic or social factors making the study participation impractical
Trial locations and contacts
1 site in 1 country.
Singapore1 site
National Neuroscience Institute - Tan Tock Seng hospital
Singapore, 308433
About this study
Official title: Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial, A Double-Blind, Randomized, Placebo-controlled, Multi-center Study
Background: Stroke is a leading cause of death and chronic serious disability worldwide.
Minocycline, a semisynthetic tetracycline, has consistently been shown in recent years to be neuroprotective in animal models of brain ischemia. Furthermore, a small, open label study done in humans with acute ischemic stroke published late last year showed that minocycline, when administered for 5 days, within 6 to 24 hours after stroke onset was highly effective in improving functional outcome even as early as 7 days after stroke onset. However, further well-conducted, randomized controlled translational studies using minocycline are currently lacking.
Read more
Objective: To determine if minocycline, administered within 3 to 48 hours after acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome at 90 days post stroke.
Methods: The investigators plan to do a multi-centre randomized, double-blind, placebo controlled trial in which ischemic stroke patients will be randomized to treatment with either oral minocycline or placebo within 3 to 48 hours of symptom onset. The primary efficacy endpoint will be the modified Rankin scale (mRS) score for all randomized subjects at 90 days.
Secondary endpoints will include improvement of the NIH Stroke Scale (NIHSS) score from baseline and Barthel index at 90 days.
NeuMAST will test the following hypotheses:
Primary Hypothesis: Minocycline, compared with placebo, when administered between 3 to 48 hours after the onset of acute ischemic stroke improves recovery and functional outcome as assessed by mRS scores on day 90 post-stroke.
Secondary Hypotheses:
- Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves recovery and functional outcome as assessed by improvement of NIHSS score on day 90 post-stroke.
- Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves functional outcome as assessed by the Barthel Index (BI) score on day 90 post-stroke.
- Minocycline, compared with placebo reduces 90 day risk of recurrent stroke, MI or death when administered between 3 to 48 hours after acute ischemic stroke onset.
A positive result will have a significant impact in the management of acute ischemic stroke and pave the way for future studies aimed at finding the optimal dose and formulation of minocycline for treating acute ischemic stroke.
Read the detailed description
- Specific Primary Objective:
- To determine if minocycline, administered within 3 to 48 hours of acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome on day 90 post stroke.
- Specific Secondary Objectives:
- To determine if minocycline administered within 3 to 48 hours of acute ischemic stroke onset is superior to placebo in reducing the 90 day risk of recurrent ischemic stroke, myocardial infarction (MI) and death.
- To study and compare the differential efficacy of minocycline administered as stated above, on the four stroke subtypes according to TOAST criteria, i.e. lacunar stroke, large vessel atherosclerosis, cardioembolic and cryptogenic stroke
- Primary Efficacy Endpoint:
The primary efficacy endpoint is the modified Rankin scale score at 90 days for all randomized patients.
Favorable outcome at day 90 is defined as achieving an mRS score of 0 to 1. Last observation carried forward (LOCF) will be used for subjects without assessments of the primary efficacy variable at Day 90. Deaths will be assigned a score of 6.
- Secondary Endpoint measures:
- NIHSS score at day 90.
- Difference of NIHSS scores between baseline and days 7 (plus or minus 2 days) and 90 post stroke. (Favorable outcome at day 90 is defined as achieving a decrease of > 6 points on NIHSS from baseline or NIHSS < 1 at day 90.
- mRS scores at days 7 (plus minus 2 days) and 30 post stroke.
- Barthel index at day 90. (A score of > 85 is defined as good outcome)
- First documentation during follow-up of ischemic stroke, myocardial infarction or death from any cause.
Recruitment of study subjects:
Acute ischemic stroke patients admitted to NNI (TTSH campus) and CGH ASU during the study period who are eligible to participate in this study based on criteria stated above will be invited to participate in this study. Approximately 1300 and 800 patients with acute ischemic stroke are admitted to NNI (TTSH campus) and CGH ASU respectively per year.
The time window for enrolment will be within 3 to 48 hours of symptom onset. For patients who are found with stroke on awakening, it will be assumed that the stroke occurred the last time that the patient was known to be normal. All eligible patients will be identified by the ward and on-call Neurology/Medical teams and referred to the study research assistants or investigators; who will then screen the patient for participation in this trial.
STUDY INTERVENTION
The assigned treatment, i.e., Minocycline 200mg or matching placebo will be administered once daily for 5 consecutive days soon after informed consent is taken and the patient is enrolled into the study.
Follow-up Assessment:
The neurologic deficits, global functional abilities and level of handicap will be scored using the NIH Stroke Scale (NIHSS) and the modified Rankin scale (mRS) at baseline and on day 7 (plus or minus 2 days).
On day 30 post-stroke, a telephone assessment with additional questions will be performed to obtain the mRS score, document any recurrent stroke, MI or death.
On day 90, in addition to a neurological evaluation, mRS and NIHSS scoring, the Barthel Index (BI) score, a measure of independence in activities of daily living, will be obtained for all subjects.
- Conditions
- Acute Stroke
- Being tested
- Minocycline (Borymycin), Matched placebo
- Keywords
- ischemic stroke recovery, minocycline, neuroprotection, acute stroke
- Medical subject headings
- Stroke, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Minocycline (Borymycin)Drug
Also called Borymycin
oral dose, 200 mg once a day for 5 days
Matched placeboDrug
Also called Placebo - cornstarch
matched placebo (cornstarch) once a day for 5 days
| Study group | Role | What they receive |
|---|---|---|
| matching placebo pill | Placebo comparator | matching placebo Receives: Drug: Matched placebo |
| Oral minocycline | Active comparator | Minocycline 200mg Receives: Drug: Minocycline (Borymycin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke
Measured: 3 months
Secondary outcomes (1)
Reduction of 90 day risk of recurrent ischemic stroke, myocardial infarction and death
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2009 (estimated)
- Study startJul 2009
- Primary completionJul 2012
- Study completionNov 2012
Why it stopped: interim analysis shows futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute StrokeStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singhealth Foundation
- Sponsor type
- Other government
- Collaborators
- National Neuroscience Institute, Changi General Hospital
- Responsible party
- Principal investigator, Dr. Rajinder Singh, Singhealth Foundation
- Investigators
- Rajinder Singh, Doctor, Principal investigator, National Neuroscience Institute - Tan Tock Seng campus and Changi hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00930020
- Sponsor's protocol ID
- SHF/CTG016/2008
- Acronym
- NeuMAST
- Status last verified
- May 2013
- First submitted
- 29 Jun 2009
- Last updated
- 3 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db.
PubMed 17909152
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial, A Double-Blind, Randomized, Placebo-controlled, Multi-center Study
- ClinicalTrials.gov ID
- NCT00930020
- Acronym / sponsor ID
- NeuMAST / SHF/CTG016/2008
- Conditions
- Acute Stroke
- Keywords
- ischemic stroke recovery, minocycline, neuroprotection, acute stroke
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: interim analysis shows futility
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Singhealth FoundationOther government
- Collaborators
- National Neuroscience Institute, Changi General Hospital
- Study start
- Jul 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 30 Jun 2009 (estimated)
- 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.
Background: Stroke is a leading cause of death and chronic serious disability worldwide.
Minocycline, a semisynthetic tetracycline, has consistently been shown in recent years to be neuroprotective in animal models of brain ischemia. Furthermore, a small, open label study done in humans with acute ischemic stroke published late last year showed that minocycline, when administered for 5 days, within 6 to 24 hours after stroke onset was highly effective in improving functional outcome even as early as 7 days after stroke onset. However, further well-conducted, randomized controlled translational studies using minocycline are currently lacking.
Objective: To determine if minocycline, administered within 3 to 48 hours after acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome at 90 days post stroke.
Methods: The investigators plan to do a multi-centre randomized, double-blind, placebo controlled trial in which ischemic stroke patients will be randomized to treatment with either oral minocycline or placebo within 3 to 48 hours of symptom onset. The primary efficacy endpoint will be the modified Rankin scale (mRS) score for all randomized subjects at 90 days.
Secondary endpoints will include improvement of the NIH Stroke Scale (NIHSS) score from baseline and Barthel index at 90 days.
NeuMAST will test the following hypotheses:
Primary Hypothesis: Minocycline, compared with placebo, when administered between 3 to 48 hours after the onset of acute ischemic stroke improves recovery and functional outcome as assessed by mRS scores on day 90 post-stroke.
Secondary Hypotheses:
- Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves recovery and functional outcome as assessed by improvement of NIHSS score on day 90 post-stroke.
- Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves functional outcome as assessed by the Barthel Index (BI) score on day 90 post-stroke.
- Minocycline, compared with placebo reduces 90 day risk of recurrent stroke, MI or death when administered between 3 to 48 hours after acute ischemic stroke onset.
A positive result will have a significant impact in the management of acute ischemic stroke and pave the way for future studies aimed at finding the optimal dose and formulation of minocycline for treating acute ischemic stroke.
Detailed description
- Specific Primary Objective:
- To determine if minocycline, administered within 3 to 48 hours of acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome on day 90 post stroke.
- Specific Secondary Objectives:
- To determine if minocycline administered within 3 to 48 hours of acute ischemic stroke onset is superior to placebo in reducing the 90 day risk of recurrent ischemic stroke, myocardial infarction (MI) and death.
- To study and compare the differential efficacy of minocycline administered as stated above, on the four stroke subtypes according to TOAST criteria, i.e. lacunar stroke, large vessel atherosclerosis, cardioembolic and cryptogenic stroke
- Primary Efficacy Endpoint:
The primary efficacy endpoint is the modified Rankin scale score at 90 days for all randomized patients.
Favorable outcome at day 90 is defined as achieving an mRS score of 0 to 1. Last observation carried forward (LOCF) will be used for subjects without assessments of the primary efficacy variable at Day 90. Deaths will be assigned a score of 6.
- Secondary Endpoint measures:
- NIHSS score at day 90.
- Difference of NIHSS scores between baseline and days 7 (plus or minus 2 days) and 90 post stroke. (Favorable outcome at day 90 is defined as achieving a decrease of > 6 points on NIHSS from baseline or NIHSS < 1 at day 90.
- mRS scores at days 7 (plus minus 2 days) and 30 post stroke.
- Barthel index at day 90. (A score of > 85 is defined as good outcome)
- First documentation during follow-up of ischemic stroke, myocardial infarction or death from any cause.
Recruitment of study subjects:
Acute ischemic stroke patients admitted to NNI (TTSH campus) and CGH ASU during the study period who are eligible to participate in this study based on criteria stated above will be invited to participate in this study. Approximately 1300 and 800 patients with acute ischemic stroke are admitted to NNI (TTSH campus) and CGH ASU respectively per year.
The time window for enrolment will be within 3 to 48 hours of symptom onset. For patients who are found with stroke on awakening, it will be assumed that the stroke occurred the last time that the patient was known to be normal. All eligible patients will be identified by the ward and on-call Neurology/Medical teams and referred to the study research assistants or investigators; who will then screen the patient for participation in this trial.
STUDY INTERVENTION
The assigned treatment, i.e., Minocycline 200mg or matching placebo will be administered once daily for 5 consecutive days soon after informed consent is taken and the patient is enrolled into the study.
Follow-up Assessment:
The neurologic deficits, global functional abilities and level of handicap will be scored using the NIH Stroke Scale (NIHSS) and the modified Rankin scale (mRS) at baseline and on day 7 (plus or minus 2 days).
On day 30 post-stroke, a telephone assessment with additional questions will be performed to obtain the mRS score, document any recurrent stroke, MI or death.
On day 90, in addition to a neurological evaluation, mRS and NIHSS scoring, the Barthel Index (BI) score, a measure of independence in activities of daily living, will be obtained for all subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| matching placebo pill | Placebo comparator | Drug: Matched placebomatching placebo |
| Oral minocycline | Active comparator | Drug: Minocycline (Borymycin)Minocycline 200mg |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Singapore citizens or permanent residents
- Age range between 21 to 80 years
- NIHSS equal or more than 5 but less than 22 at time of admission
- Clinical diagnosis of acute ischemic stroke according to WHO criteria
- Onset of stroke between 3 to 48 hours prior to start of treatment
Key exclusion criteria (14 listed)
- Long term residents of Institutions and Nursing homes
- Patients with significant baseline cognitive dysfunction
- Patients with hemorrhagic stroke
- Pre-stroke MRS more than 1
- Evidence of other disease of the CNS (i.e., brain tumor, CNS infections)
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 (Borymycin)Also: Borymycinoral dose, 200 mg once a day for 5 days | Drug | Oral minocycline |
| Matched placeboAlso: Placebo - cornstarchmatched placebo (cornstarch) once a day for 5 days | Drug | matching placebo pill |
Primary outcome
Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke
Time frame: 3 months
1 secondary outcome
Reduction of 90 day risk of recurrent ischemic stroke, myocardial infarction and death
Time frame: 3 months
Results and safety
The study was stopped early (reason given: interim analysis shows futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2013.
- Background: PubMed 17909152Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db.
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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. This study is not recruiting at the moment.
Rajinder Singh, Doctor principal investigator
National Neuroscience Institute - Tan Tock Seng campus and Changi hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Minocycline (Borymycin) in people with Acute Stroke, run by Singhealth Foundation at 1 site in Singapore.
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 14 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: stopped early, as of the sponsor's last update on 3 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: interim analysis shows futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00930020, which also lists 1 linked publication.
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 3 Jun 2013; AzTrials last refreshed its copy on 8 Nov 2026.