Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial
Information source: Singhealth Foundation
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Stroke
Intervention: Minocycline (Borymycin) (Drug); Matched placebo (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: Singhealth Foundation Official(s) and/or principal investigator(s): Rajinder Singh, Doctor, Principal Investigator, Affiliation: National Neuroscience Institute - Tan Tock Seng campus and Changi hospital
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. 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:
1. 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.
2. 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.
3. 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.
Clinical Details
Official title: Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial, A Double-Blind, Randomized, Placebo-controlled, Multi-center Study
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke
Secondary outcome: Reduction of 90 day risk of recurrent ischemic stroke, myocardial infarction and death
Detailed description:
A) Specific Primary Objective:
1. 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.
B) Specific Secondary Objectives:
1. 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.
2. 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
C) 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.
D) Secondary Endpoint measures:
1. NIHSS score at day 90.
2. 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.
3. mRS scores at days 7 (plus minus 2 days) and 30 post stroke.
4. Barthel index at day 90. (A score of > 85 is defined as good outcome)
5. 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.
Eligibility
Minimum age: 21 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Locations and Contacts
National Neuroscience Institute - Tan Tock Seng hospital, Singapore 308433, Singapore
Additional Information
Related 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.
Starting date: July 2009
Last updated: May 30, 2013
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