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Trial record 9 of 88 for:    "Brain Diseases" AND "Multiple System Atrophy"

Study of Rifampicin in Multiple System Atrophy (MSA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01287221
Recruitment Status : Terminated (DSMB recommended stopping the study after an interim analysis of the primary endpoint revealed that futility criteria were met.)
First Posted : February 1, 2011
Results First Posted : March 28, 2014
Last Update Posted : March 28, 2014
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Vanderbilt University
Rare Disease Research Network Autonomic Consortium
Information provided by (Responsible Party):
Phillip Low, Mayo Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Multiple System Atrophy
Interventions Drug: Rifampicin
Drug: placebo
Enrollment 100
Recruitment Details Subjects were enrolled from 10 specialized tertiary centers in the United States from April 2011 through April 2012.
Pre-assignment Details  
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Period Title: Overall Study
Started 50 50
Completed 3 Months Follow-up 49 50
Completed 6 Months Follow-up 47 43
Completed 9 Months Follow-up 42 40
Completed 12 Months Follow-up 40 39
Completed 46 45
Not Completed 4 5
Reason Not Completed
Lack of Perceived Benefit             1             1
Adverse Event             3             3
Withdrawal by Subject             0             1
Arm/Group Title Rifampicin Placebo Total
Hide Arm/Group Description Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2). Total of all reporting groups
Overall Number of Baseline Participants 50 50 100
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 50 participants 100 participants
60.9  (7.8) 61.1  (9.2) 61.0  (8.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 50 participants 100 participants
Female
23
  46.0%
16
  32.0%
39
  39.0%
Male
27
  54.0%
34
  68.0%
61
  61.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 50 participants 50 participants 100 participants
50 50 100
Multiple System Atrophy (MSA) Type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 50 participants 100 participants
Parkinsonian (MSA-P) 19 22 41
Cerebellar (MSA-C) 31 28 59
Certainty of Multiple System Atrophy (MSA) Diagnosis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 50 participants 100 participants
Probable 31 34 65
Possible 19 16 35
[1]
Measure Description:

Criteria for probable MSA:1)Autonomic failure involving urinary incontinence or an orthostatic decrease of blood pressure within 3 min of standing by at least 30 mm Hg systolic or 15 mm Hg diastolic and 2)Poorly levodopa-responsive parkinsonism, or 3) cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction).

Criteria for possible MSA:1)Parkinsonism or 2)cerebellar syndrome and 3)at least one feature suggesting autonomic dysfunction (unexplained urinary urgency, frequent bladder emptying, erectile dysfunction, orthostatic hypotension.)

1.Primary Outcome
Title Rate of Change From Baseline to 12 Months in the Total Unified Multiple System Atrophy Rating Scale (UMSARS) Part I Score (Minus Question 11)
Hide Description

UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part I could range from 0 (normal) to 48 (extreme dysfunction).

Participant-specific rate of change in points per month was estimated using slope estimate from least square regression where for each participant, their UMSARS I scores were plotted over time measured in months.

Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles and no imputations were done for any missing values or slope estimates. All randomized participants who took at least two doses of the study drug were included in the principal efficacy analysis. One subject on the Rifampicin arm did not return after the baseline visit.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 49 50
Mean (Standard Deviation)
Unit of Measure: units on a scale per month
0.5  (0.7) 0.5  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to 12 Months in UMSARS Part I Score (Minus Question 11)
Hide Description UMSARS is a scale measuring disease progression that comprises 4 parts, only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part I could range from 0 (normal) to 48 (extreme dysfunction).
Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.2  (5.6) 5.6  (5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to 12 Months in UMSARS Part II
Hide Description UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part II could range from 0 (normal) to 56 (extreme dysfunction).
Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
7.0  (6.3) 5.4  (6.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to 12 Months in Total UMSARS (i.e., UMSARS Part I Minus Question 11 + UMSARS Part II)
Hide Description UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for total UMSARS Parts I minus Question 11 + Part II could range from 0 (normal) to 104 (extreme dysfunction).
Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
12.9  (10.6) 10.8  (10.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Rate of Change From Baseline to 12 Months in Total UMSARS (i.e., UMSARS Part I Minus Question 11 + UMSARS Part II) Using Slope Estimate
Hide Description

UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for total UMSARS Parts I minus Question 11 + Part II could range from 0 (normal) to 104 (extreme dysfunction).

Participant-specific rate of change in points per month was estimated using slope estimate from least square regression where for each participant, their total UMSARS scores were plotted over time measured in months.

Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 45 43
Mean (Standard Deviation)
Unit of Measure: units on a scale per month
1.1  (1.0) 1.2  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to 12 Months in the COMPASS-Select Scale
Hide Description The composite autonomic symptoms score (COMPASS) provides a score of autonomic symptom severity with appropriate weighting. In the COMPASS_select, symptoms are confined to 6 select domains of symptoms. The version of the COMPASS-Select used (06-09-2009 v1) has 46 questions, with multiple parts, scores ranging from "much worse" to "no such symptoms." Scores could range from 0 (no such symptoms) to 85 (much worse).
Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 39 38
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.9  (16.5) 4.6  (13.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Change in the COMPASS-Select-Change Scale From Baseline to 12 Months
Hide Description The change in COMPASS is a derivative of COMPASS and evaluates the change in symptoms over time on selected domains of symptoms as a function of natural history or intervention therapy. The focus is on 7 selected domains. The version of the COMPASS-Change -Select Scale used (06-09-2009 Ver. 1) has 16 questions, with multiple parts, scores ranging from "much worse" to "no such symptoms." The score could range from 0 (no such symptoms) to 94 (much worse).
Time Frame baseline, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study.
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description:
Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months.
Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
Overall Number of Participants Analyzed 39 38
Mean (Standard Deviation)
Unit of Measure: units on a scale
41.4  (33.8) 32.1  (35.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rifampicin, Placebo
Comments Given that there were no imbalances identified between the two groups at baseline and the slope estimates for the two treatment arms did not support assumption of normality, the analysis was performed using Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Adverse events were to be recorded from the time a participant signed the informed consent form and throughout the 12 months of the study, even if they prematurely discontinued the study drug.
Adverse Event Reporting Description The attribution of serious adverse events was determined by the Medical Review Officer, whereas the attribution of non-serious adverse events was determined by the reporter.
 
Arm/Group Title Rifampicin Placebo
Hide Arm/Group Description Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2).
All-Cause Mortality
Rifampicin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rifampicin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/50 (6.00%)      12/50 (24.00%)    
Cardiac disorders     
Thrombosis/thrombus/embolism  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Cardiac ischemia/infarction  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Vessel injury - artery  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Death not associated with CTCAE Term  1 [1]  0/50 (0.00%)  0 2/50 (4.00%)  2
Cardiac general - other  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Hepatobiliary disorders     
Liver Dysfunction/failure  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Infections and infestations     
Infection with unknown ANC  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Joint Function  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Musculoskeletal/soft tissue - other  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Nervous system disorders     
Neurology - other  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Psychiatric disorders     
Mood Alteration  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Renal and urinary disorders     
Renal/genitourinary - other  1  0/50 (0.00%)  0 1/50 (2.00%)  2
Renal Failure  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Respiratory, thoracic and mediastinal disorders     
Adult Respiratory Distress Syndrome (ARDS)  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Obstruction/stenosis of airway  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Vascular disorders     
Vomiting - aspirated/stroke  1 [2]  0/50 (0.00%)  0 1/50 (2.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (Unspecified)
[1]
2 subjects died post-study, unrelated to study drug or placebo.
[2]
Subject hospitalized for hernia repair surgery, and surgery went well. Subject was being cleaned by family and vomited, aspirated, and stroked. Subject experienced multiple system failure and was declared dead.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rifampicin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/50 (62.00%)      26/50 (52.00%)    
Blood and lymphatic system disorders     
Edema: limb  1  1/50 (2.00%)  1 3/50 (6.00%)  3
Lymphopenia  1  1/50 (2.00%)  2 0/50 (0.00%)  0
Hemoglobin  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Cardiac disorders     
Prolonged QTc Interval  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Endocrine disorders     
Glucose, serum-low  1 [1]  0/50 (0.00%)  0 1/50 (2.00%)  1
Endocrine - other  1  2/50 (4.00%)  2 0/50 (0.00%)  0
Glucose, serum-high  1 [2]  0/50 (0.00%)  0 2/50 (4.00%)  2
Hepatobiliary/Pancreas - other  1  1/50 (2.00%)  1 1/50 (2.00%)  1
Eye disorders     
Eyelid dysfunction  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Vision - photophobia  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Vision - blurred vision  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Ophthalmoplegia/diplopia (double vision)  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Gastrointestinal disorders     
Nausea  1  6/50 (12.00%)  6 1/50 (2.00%)  1
Heartburn/dyspepsia  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Diarrhea  1  3/50 (6.00%)  3 0/50 (0.00%)  0
Gastrointestinal - other  1  5/50 (10.00%)  5 4/50 (8.00%)  4
Constipation  1  3/50 (6.00%)  3 0/50 (0.00%)  0
Vomiting  1  2/50 (4.00%)  2 0/50 (0.00%)  0
General disorders     
Speech impairment  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Pain  1  6/50 (12.00%)  6 2/50 (4.00%)  3
Fatigue  1  3/50 (6.00%)  3 2/50 (4.00%)  2
Constitutional Symptoms - other  1  0/50 (0.00%)  0 3/50 (6.00%)  3
Taste Alteration (dysgeusia)  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Dizziness  1  3/50 (6.00%)  4 1/50 (2.00%)  1
Bruising (in absence of Grade 3 or 4 thrombocytopenia)  1  0/50 (0.00%)  0 2/50 (4.00%)  2
Metabolic/Laboratory - other  1  4/50 (8.00%)  5 4/50 (8.00%)  8
Syncope (fainting)  1  1/50 (2.00%)  1 1/50 (2.00%)  1
Allergic reaction/hypersensitivity  1 [3]  0/50 (0.00%)  0 1/50 (2.00%)  1
Dysphagia (difficulty swallowing)  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Rigors/chills  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Weight loss  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Somnolence/depressed level of consciousness  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Dry mouth/salivary gland (xerostomia)  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Hepatobiliary disorders     
ALT, serum glutamic pyruvic transaminase (SGPT)  1  1/50 (2.00%)  1 2/50 (4.00%)  6
AST, serum glutamic oxaloacetic transaminase (SGOT)  1  0/50 (0.00%)  0 1/50 (2.00%)  2
Liver dysfunction/failure (clinical)  1  2/50 (4.00%)  2 0/50 (0.00%)  0
Immune system disorders     
Leukocytes  1 [4]  1/50 (2.00%)  1 0/50 (0.00%)  0
Neutrophils/granulocytes  1 [5]  1/50 (2.00%)  1 0/50 (0.00%)  0
Infections and infestations     
Wound complication, non-infectious  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Infection with unknown  1 [6]  2/50 (4.00%)  2 1/50 (2.00%)  4
Musculoskeletal and connective tissue disorders     
Musculoskeletal/soft tissue - other  1  1/50 (2.00%)  1 3/50 (6.00%)  4
Tremor  1  2/50 (4.00%)  2 1/50 (2.00%)  1
Joint Function  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Bone: spine - scoliosis  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Fracture  1  1/50 (2.00%)  2 1/50 (2.00%)  1
Muscle weakness, generalized or specific area (not due to neuropathy)  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Nervous system disorders     
Encephalopathy  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Neurology - other  1  4/50 (8.00%)  4 5/50 (10.00%)  5
Ataxia  1 [7]  0/50 (0.00%)  0 2/50 (4.00%)  2
Neuropathy: sensory  1  1/50 (2.00%)  1 0/50 (0.00%)  0
CNS cerebrovascular ischemia  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Psychiatric disorders     
Mood alteration  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Memory Impairment  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Renal and urinary disorders     
Renal/Genitourinary - Other  1  3/50 (6.00%)  4 8/50 (16.00%)  12
Urinary frequency/urgency  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Creatinine  1  1/50 (2.00%)  1 3/50 (6.00%)  3
Cystitis  1  2/50 (4.00%)  2 0/50 (0.00%)  0
Urinary retention  1 [8]  2/50 (4.00%)  2 1/50 (2.00%)  1
Urine color change  1  5/50 (10.00%)  5 6/50 (12.00%)  6
Respiratory, thoracic and mediastinal disorders     
Nasal Cavity/paranasal sinus reactions  1  0/50 (0.00%)  0 2/50 (4.00%)  2
Pneumonitis/pulmonary infiltrates  1  1/50 (2.00%)  2 0/50 (0.00%)  0
Adult Respiratory Distress Syndrome (ARDS)  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Pulmonary/Upper Respiratory - other  1  2/50 (4.00%)  3 2/50 (4.00%)  2
Obstruction/stenosis of airway  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Dyspnea (shortness of breath)  1  1/50 (2.00%)  1 1/50 (2.00%)  1
Skin and subcutaneous tissue disorders     
Hyperpigmentation  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Sweating (diasporesis)  1  1/50 (2.00%)  1 0/50 (0.00%)  0
Dermatology/Skin - other  1  1/50 (2.00%)  1 3/50 (6.00%)  3
Vascular disorders     
Petechiae/purpura  1 [9]  1/50 (2.00%)  1 0/50 (0.00%)  0
Hypotension  1  2/50 (4.00%)  2 0/50 (0.00%)  0
Hemorrhage/bleeding - other  1  1/50 (2.00%)  1 2/50 (4.00%)  2
Blood/Bone marrow - other  1  1/50 (2.00%)  1 1/50 (2.00%)  1
International Normalized Ratio (INR) of prothrombin time  1  0/50 (0.00%)  0 1/50 (2.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (Unspecified)
[1]
hypoglycemia
[2]
(hyperglycemia)
[3]
(including drug fever)
[4]
Total White Blood Count (WBC)
[5]
Absolute neutrophil count (ANC)/Absolute granulocyte count (AGC)
[6]
ANC
[7]
lack of voluntary coordination of muscle movements
[8]
(including neurogenic bladder)
[9]
hemorrhage/bleeding into skin or mucosa
The study was terminated early; the Data Safety and Monitoring Board recommended stopping the study after an interim analysis of the primary endpoint revealed that futility criteria were met.
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.
Results Point of Contact
Name/Title: Dr. Phillip A. Low
Organization: Mayo Clinic
Phone: 507-284-3375
EMail: low@mayo.edu
Responsible Party: Phillip Low, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01287221     History of Changes
Other Study ID Numbers: 10-003108
P01NS044233 ( U.S. NIH Grant/Contract )
U54NS065736 ( U.S. NIH Grant/Contract )
First Submitted: January 28, 2011
First Posted: February 1, 2011
Results First Submitted: July 2, 2013
Results First Posted: March 28, 2014
Last Update Posted: March 28, 2014