Trial Outcomes & Findings for Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke (NCT NCT00630396)

Last Updated: 2012-01-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

60 participants

Primary outcome timeframe

3 days

Results posted on

2012-01-13

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	60
Overall Study COMPLETED	53
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Death	4
Overall Study Lost to Follow-up	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Minocycline n=60 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants
Age Continuous Overall age	65 years STANDARD_DEVIATION 13.7 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants
Weight	81.6 Kg STANDARD_DEVIATION 21.6 • n=5 Participants
Subjects receiving t-PA then minocycline Total amount of subjects that received t-PA	36 Participants n=5 Participants
Subjects receiving t-PA then minocycline Total amount of subjects that did not receive t-PA	24 Participants n=5 Participants
NIH Stroke Scale at baseline	8.7 Units on a scale STANDARD_DEVIATION 5.8 • n=5 Participants
Symptom onset to study drug infusion time	307.4 minutes STANDARD_DEVIATION 50.0 • n=5 Participants

PRIMARY outcome

Timeframe: 3 days

Outcome measures

Outcome measures
Measure	Minocycline n=60 Participants 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.
Maximally Tolerated Dose of IV Minocycline	10 mg/kg

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Minocycline n=176 blood samples 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.
Half-life of IV Minocycline	23.8 hours Standard Error 1.9

SECONDARY outcome

Timeframe: 3 months

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.

Outcome measures

Outcome measures
Measure	Minocycline n=60 Participants 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.
90 Day Modified Rankin Scale Score 90 day mRS score of 0 overall	15 Participants
90 Day Modified Rankin Scale Score 90 day mRS score of 1 overall	15 Participants
90 Day Modified Rankin Scale Score 90 day mRS score of 2 overall	9 Participants
90 Day Modified Rankin Scale Score 90 day mRS score of 3 overall	11 Participants
90 Day Modified Rankin Scale Score 90 day mRS score of 4 overall	2 Participants
90 Day Modified Rankin Scale Score 90 day mRS score of 5 overall	3 Participants
90 Day Modified Rankin Scale Score 90 day mRS score of 6 overall	5 Participants

Adverse Events

Minocycline

Serious events: 29 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Minocycline n=60 participants at risk 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.
Nervous system disorders Death	8.3% 5/60 • Number of events 5 • 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.
Nervous system disorders Transient Ischemic Attack	1.7% 1/60 • Number of events 1 • 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.
Infections and infestations Urinary Tract Infection	5.0% 3/60 • Number of events 3 • 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.
Nervous system disorders Acute Ischemic Stroke	5.0% 3/60 • Number of events 3 • 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.
Nervous system disorders Worsening hallucinations and agitation	1.7% 1/60 • Number of events 1 • 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.
Cardiac disorders Congestive Heart Failure exacerbation	1.7% 1/60 • Number of events 1 • 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.
Cardiac disorders Rule out myocardial infarction (chest pain, nausea, shortness of breath)	1.7% 1/60 • Number of events 1 • 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.
Cardiac disorders Congestive Heart Failure	1.7% 1/60 • Number of events 1 • 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.
Nervous system disorders Neuroworsening	5.0% 3/60 • Number of events 3 • 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.
Musculoskeletal and connective tissue disorders Left hip fracture	1.7% 1/60 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Pulmonary emboli secondary to left lower extremity deep vein thrombosis	1.7% 1/60 • Number of events 1 • 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.
Surgical and medical procedures Carotid endarterectomy	1.7% 1/60 • Number of events 1 • 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.
Infections and infestations Rule out pneumonia	1.7% 1/60 • Number of events 1 • 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.
Reproductive system and breast disorders Scrotal edema	1.7% 1/60 • Number of events 1 • 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.
Gastrointestinal disorders Stomach cancer	1.7% 1/60 • Number of events 1 • 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.
Cardiac disorders Paroxysmal atrial fibrillation	1.7% 1/60 • Number of events 1 • 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.
Psychiatric disorders Depression/suicide attempt	1.7% 1/60 • Number of events 1 • 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.
Renal and urinary disorders Hypotension	1.7% 1/60 • Number of events 1 • 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.
Nervous system disorders Intracerebral Hemorrhage	1.7% 1/60 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	Minocycline n=60 participants at risk 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.
Nervous system disorders Hemorrhagic transformation	5.0% 3/60 • Number of events 3 • 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.
Nervous system disorders Neurological worsening	5.0% 3/60 • Number of events 3 • 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.
Gastrointestinal disorders GI Symptoms	20.0% 12/60 • Number of events 22 • 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.
Skin and subcutaneous tissue disorders Skin reactions	21.7% 13/60 • Number of events 17 • 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.
Infections and infestations Urinary Tract Infection	5.0% 3/60 • Number of events 3 • 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.
Cardiac disorders Atrial Fibrillation	5.0% 3/60 • Number of events 3 • 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.
Renal and urinary disorders Elevated liver enzymes	6.7% 4/60 • Number of events 4 • 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.
Blood and lymphatic system disorders Reduced platelet count	6.7% 4/60 • Number of events 4 • 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.
Nervous system disorders Headache	25.0% 15/60 • Number of events 15 • 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.
Nervous system disorders Vertigo	5.0% 3/60 • Number of events 4 • 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.
Renal and urinary disorders Hypotension	6.7% 4/60 • Number of events 4 • 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.
General disorders Pain	16.7% 10/60 • Number of events 13 • 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.
Cardiac disorders Chest pain	6.7% 4/60 • Number of events 4 • 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.
Cardiac disorders Tachycardia	5.0% 3/60 • Number of events 3 • 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.
Infections and infestations Aspiration pneumonia	5.0% 3/60 • Number of events 3 • 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.
General disorders Edema	5.0% 3/60 • Number of events 4 • 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.

Additional Information

David Hess, MD

Georgia Health Sciences University

Phone: 706-721-1691

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place