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| ID | Type | Description | Link |
|---|---|---|---|
| 07-02-202 | Other Identifier | GHSU Human Assurance Committee number |
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
| University of Kentucky | OTHER |
| Oregon Health and Science University | OTHER |
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The primary aim of this study is to find out which of 4 different doses of minocycline are safe and well tolerated so that we will know the optimal dose to test in future patients.
Minocycline is a widely used antibiotic and is approved by the Food and Drug Administration (FDA) for treatment of infections and acne. However, doctors do not know whether minocycline will work in stroke patients. Its use in stroke patients is experimental. There is a lot of information from experimental stroke studies in animals that minocycline lessens the damage from a stroke and the animals recover better. Since minocycline is generally a very safe drug in humans and does not have a lot of side effects, investigators at Georgia Health Sciences University (formerly the Medical College of Georgia) believe that it might be a safe and effective drug to improve the outcome in patients with stroke.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | Dose level 1 = 3mg/kg intravenous (IV) initial dose, followed by 1.5mg/kg every 12 hours times 5 more doses. Dose level 2 = 4.5mg/kg intravenous (IV) initial dose, followed by 2.25mg/kg every 12 hours times 5 more doses. Dose level 3 = 6 mg/kg intravenous (IV) initial dose, followed by 3 mg/kg every 12 hours times 5 more doses. Dose level 4 = 10 mg/kg intravenous (IV) initial dose, followed by 5 mg/kg every 12 hours times 5 more doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximally Tolerated Dose of IV Minocycline | Investigators closely monitored each subject for evidence of minocycline intolerance. All adverse events were immediately reported for a decision whether to discontinue the study medication and/or reduce the dose. A computer program was used to determine the maximum tolerated dose. After entering information regarding doses and expected toxicities, results for each subject as they were collected were entered. The computer program informed as to (de)escalation, or maintenance of the same dose in the subsequent cohort of enrolled patients. | 3 days |
| Measure | Description | Time Frame |
|---|---|---|
| Half-life of IV Minocycline | In eligible patients enrolled at Georgia Health Sciences University, blood samples were drawn for quantification of minocycline serum concentrations. This enabled the study team to determine the half life of the study drug. | 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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David C Hess, MD | Augusta University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky | Lexington | Kentucky | 40506-0057 | United States | ||
| Oregon Health & Science University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20705929 | Result | 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. doi: 10.1161/STROKEAHA.110.582601. Epub 2010 Aug 12. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximally Tolerated Dose of IV Minocycline | Investigators closely monitored each subject for evidence of minocycline intolerance. All adverse events were immediately reported for a decision whether to discontinue the study medication and/or reduce the dose. A computer program was used to determine the maximum tolerated dose. After entering information regarding doses and expected toxicities, results for each subject as they were collected were entered. The computer program informed as to (de)escalation, or maintenance of the same dose in the subsequent cohort of enrolled patients. | Posted | Number | mg/kg | 3 days |
|
Adverse Events were collected for one year and seven months. This time period started when the first subject was enrolled and lasted until the 90 day follow-up was completed for the last subject enrolled.
Investigators closely monitored each patient for evidence of study drug intolerance, particularly focusing on dizziness, gastrointestinal complaints, and infusion reactions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Nervous system disorders | Systematic Assessment | Five individuals died during the study. Three occurred during hospitalization(all three were attributed to the patient's underlying illness). The other two deaths after discharge were from gastric cancer and worsening congestive heart failure. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemorrhagic transformation | Nervous system disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Hess, MD | Georgia Health Sciences University | 706-721-1691 | dhess@georgiahealth.edu |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| D007511 | Ischemia |
| C562573 | cyclopia sequence |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| 90 Day Modified Rankin Scale Score | The modified Rankin Scale (mRS) was performed in person at the 90 day clinic follow-up appointment. The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6. 0 represents no symptoms. 1 represents no significant disability. 2 represents slight disability. 3 represents moderate disability. 4 represents moderately severe disability. 5 represents severe disability. 6 represents death. | 3 months |
| Portland |
| Oregon |
| 97239 |
| United States |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | Kg |
|
| Subjects receiving t-PA then minocycline | 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. | Number | Participants |
|
| NIH Stroke Scale at baseline | 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. | Mean | Standard Deviation | Units on a scale |
|
| Symptom onset to study drug infusion time | This is the average time from when the patient was "last known to be normal" to the moment the study drug began infusing intravenously. | Mean | Standard Deviation | minutes |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Half-life of IV Minocycline | In eligible patients enrolled at Georgia Health Sciences University, blood samples were drawn for quantification of minocycline serum concentrations. This enabled the study team to determine the half life of the study drug. | Posted | Mean | Standard Error | hours | 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. | blood samples | Participants |
|
|
|
| Secondary | 90 Day Modified Rankin Scale Score | The modified Rankin Scale (mRS) was performed in person at the 90 day clinic follow-up appointment. The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6. 0 represents no symptoms. 1 represents no significant disability. 2 represents slight disability. 3 represents moderate disability. 4 represents moderately severe disability. 5 represents severe disability. 6 represents death. | Posted | Number | Participants | 3 months |
|
|
|
| 29 |
| 60 |
| 50 |
| 60 |
|
| Transient Ischemic Attack | Nervous system disorders | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
|
| Acute Ischemic Stroke | Nervous system disorders | Systematic Assessment |
|
| Worsening hallucinations and agitation | Nervous system disorders | Systematic Assessment |
|
| Congestive Heart Failure exacerbation | Cardiac disorders | Systematic Assessment |
|
| Rule out myocardial infarction (chest pain, nausea, shortness of breath) | Cardiac disorders | Systematic Assessment | Subject complained of chest pain at home. Subject was hospitalized. Cardiac enzymes and chest x-ray were negative. Chest pain resolved, and myocardial infarction was ruled out. |
|
| Congestive Heart Failure | Cardiac disorders | Systematic Assessment |
|
| Neuroworsening | Nervous system disorders | Systematic Assessment | Neuroworsening is an increase in the severity of a subject's stroke (defined as an increase in a subjects National Institutes of Health Stroke Scale by 4 or more points). |
|
| Left hip fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pulmonary emboli secondary to left lower extremity deep vein thrombosis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Carotid endarterectomy | Surgical and medical procedures | Systematic Assessment |
|
| Rule out pneumonia | Infections and infestations | Systematic Assessment | Subject hospitalized and thought to have left lower lobe pneumonia based on chest x-ray. He received 1 dose of 2 different antibiotics. Subject improved; however, subject not thought to have pneumonia. Subject was discharged home without antibiotics. |
|
| Scrotal edema | Reproductive system and breast disorders | Systematic Assessment |
|
| Stomach cancer | Gastrointestinal disorders | Systematic Assessment |
|
| Paroxysmal atrial fibrillation | Cardiac disorders | Systematic Assessment |
|
| Depression/suicide attempt | Psychiatric disorders | Systematic Assessment |
|
| Hypotension | Renal and urinary disorders | Systematic Assessment |
|
| Intracerebral Hemorrhage | Nervous system disorders | Systematic Assessment |
|
| Neurological worsening | Nervous system disorders | Systematic Assessment |
|
| GI Symptoms | Gastrointestinal disorders | Systematic Assessment | Nausea, vomiting, diarrhea, stomach pain, epigastric pain, abdominal pain, excessive belching, worsening dyspepsia |
|
| Skin reactions | Skin and subcutaneous tissue disorders | Systematic Assessment | Phlebitis (0), Burning at the IV site during infusion, Stage I & II skin breakdown, rash and bruising. |
|
| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Elevated liver enzymes | Renal and urinary disorders | Systematic Assessment | Elevated liver enzymes (2), elevated LFTs (1), and hepatic toxicity (1). |
|
| Reduced platelet count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment | There were 13 complaints of headache and 2 complaints of worsening of headache. |
|
| Vertigo | Nervous system disorders | Systematic Assessment | Disequilibrium (1) and dizziness (3) |
|
| Hypotension | Renal and urinary disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment | Complaints of pain occurred in the: shoulder, neck, foot, knee, back, hand, leg, left lower extremity and penis (1). |
|
| Chest pain | Cardiac disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Aspiration pneumonia | Infections and infestations | Systematic Assessment |
|
| Edema | General disorders | Systematic Assessment | Peripheral edema (1 case); mild pulmonary edema (1 case); bilateral upper extremity edema (1 case); lower extremity edema (1 case) |
|
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|---|
|
| 90 day mRS score of 3 overall |
|
| 90 day mRS score of 4 overall |
|
| 90 day mRS score of 5 overall |
|
| 90 day mRS score of 6 overall |
|