Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke - Study Results

Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke (MINOS)

This study has been completed.

Study NCT00630396 Information provided by Georgia Health Sciences University

First Received on February 28, 2008. Last Updated on December 9, 2011 History of Changes

Results First Received: August 1, 2011

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Stroke, Acute
Intervention:	Drug: Minocycline

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment occurred from June 3, 2008 to October 10, 2009. The study was completed ahead of schedule. Study subjects were enrolled in each recruiting centers' Emergency Department or stroke intensive care unit. Many subjects came as transfers from rural or outside hospitals to one of the enrolling centers for further care and study participation.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Potential patients that met all of the inclusion criteria, did not meet any of the exclusion criteria, and were willing to participate were enrolled in the study. All study subjects were given one of the four doses of minocycline. The dose of minocycline given was assigned by a computer program.

Reporting Groups

	Description
Minocycline	All 60 participants were treated with minocycline. 11 participants were treated at 3mg/kg, 4 were treated at 4.5mg/kg, 4 were treated at 6mg/kg, and 41 were treated at 10mg/kg.

Participant Flow: Overall Study

	Minocycline
STARTED	60
COMPLETED	53
NOT COMPLETED	7
Death	4
Lost to Follow-up	3

Baseline Characteristics

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Reporting Groups

	Description
Minocycline	All 60 participants were treated with minocycline. 11 participants were treated at 3mg/kg, 4 were treated at 4.5mg/kg, 4 were treated at 6mg/kg, and 41 were treated at 10mg/kg.

Baseline Measures

	Minocycline
Number of Participants [units: participants]	60
Age [units: Participants]
<=18 years	0
Between 18 and 65 years	30
>=65 years	30
Age [units: years] Mean ± Standard Deviation
Overall age	65 ± 13.7
Gender [units: participants]
Female	28
Male	32
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	9
White	50
More than one race	0
Unknown or Not Reported	0
Region of Enrollment [units: participants]
United States	60
Weight [units: Kg] Mean ± Standard Deviation	81.6 ± 21.6
Subjects receiving t-PA then minocycline ^[1] [units: Participants]
Total amount of subjects that received t-PA	36
Total amount of subjects that did not receive t-PA	24
NIH Stroke Scale at baseline ^[2] [units: Units on a scale] Mean ± Standard Deviation	8.7 ± 5.8
Symptom onset to study drug infusion time ^[3] [units: minutes] Mean ± Standard Deviation	307.4 ± 50.0

[1]	Patients that received tissue plasminogen activator (tPA) were also eligible for the MINOS trial. Once tPA had finished infusing, the research team would commence with the study drug infusion.
[2]	The National Institutes of Health (NIH) Stroke Scale was designed to assess, score, and reliably communicate the level of impairment in a stroke patient. The maximum score is a 42, and the minimum score is a 0. A 42 represents the most severe stroke as scored by the NIH Stroke Scale.
[3]	This is the average time from when the patient was "last known to be normal" to the moment the study drug began infusing intravenously.

Outcome Measures

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1. Primary:

Maximally Tolerated Dose of IV Minocycline [ Time Frame: 3 days ]

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2. Secondary:

Half-life of IV Minocycline [ Time Frame: For each subject blood samples were drawn before dose #1 and one hour after starting dose #1. Additional blood was drawn 1, 6, 12, 24, 48, and 72 hours after starting dose #6, which lasted approximately 6 days. ]

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3. Secondary:

90 Day Modified Rankin Scale Score [ Time Frame: 3 months ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Some statistical tests could not be performed due to small sample size in the 4.5 and 6mg/kg dose tiers. The modified continual reassessment method (CRM) failed to identify the maximum tolerated dose of intravenous minocycline.

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data

Some statistical tests could not be performed due to small sample size in the 4.5 and 6mg/kg dose tiers.

The modified continual reassessment method (CRM) failed to identify the maximum tolerated dose of intravenous minocycline.

Results Point of Contact:

Name/Title: David Hess, MD
Organization: Georgia Health Sciences University
phone: 706-721-1691
e-mail: dhess@georgiahealth.edu

Publications of Results:

Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, Hall CE, Switzer JA, Ergul A, Hess DC. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010 Oct;41(10):2283-7. Epub 2010 Aug 12.

Responsible Party:	David Hess, MD, Georgia Health Sciences University
ClinicalTrials.gov Identifier:	NCT00630396 History of Changes
Other Study ID Numbers:	RO1 NS055728-01A1, 07-02-202
Study First Received:	February 28, 2008
Results First Received:	August 1, 2011
Last Updated:	December 9, 2011
Health Authority:	United States: Food and Drug Administration