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Progesterone for the Treatment of Traumatic Brain Injury III (ProTECT)

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ClinicalTrials.gov Identifier: NCT00822900
Recruitment Status : Terminated (futility: low conditional power to demonstrate benefit of progesterone)
First Posted : January 15, 2009
Results First Posted : July 3, 2015
Last Update Posted : January 20, 2016
Sponsor:
Collaborators:
Medical University of South Carolina
Neurological Emergencies Treatment Trials Network (NETT)
Information provided by (Responsible Party):
David Wright, Emory University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Traumatic Brain Injury
Interventions Drug: Progesterone
Drug: Placebo
Enrollment 882
Recruitment Details A total of 882 patients underwent randomization at 49 trauma centers in the United States between April 5, 2010, and October 30, 2013. 442 patients were randomized to Progesterone Arm and 440 were randomized to Placebo Arm.
Pre-assignment Details  
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 442 440
Completed 334 347
Not Completed 108 93
Reason Not Completed
Withdrawal by Subject             14             14
Lost to Follow-up             9             9
Death             83             69
Became a ward of the state             2             1
Arm/Group Title Progesterone Placebo Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 442 440 882
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 442 participants 440 participants 882 participants
39  (18) 38  (17) 39  (18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 442 participants 440 participants 882 participants
Female
118
  26.7%
114
  25.9%
232
  26.3%
Male
324
  73.3%
326
  74.1%
650
  73.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 442 participants 440 participants 882 participants
Hispanic or Latino
61
  13.8%
64
  14.5%
125
  14.2%
Not Hispanic or Latino
347
  78.5%
343
  78.0%
690
  78.2%
Unknown or Not Reported
34
   7.7%
33
   7.5%
67
   7.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 442 participants 440 participants 882 participants
American Indian or Alaska Native
5
   1.1%
2
   0.5%
7
   0.8%
Asian
20
   4.5%
22
   5.0%
42
   4.8%
Native Hawaiian or Other Pacific Islander
1
   0.2%
2
   0.5%
3
   0.3%
Black or African American
70
  15.8%
64
  14.5%
134
  15.2%
White
330
  74.7%
331
  75.2%
661
  74.9%
More than one race
3
   0.7%
6
   1.4%
9
   1.0%
Unknown or Not Reported
13
   2.9%
13
   3.0%
26
   2.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 442 participants 440 participants 882 participants
442 440 882
Index GCS score at randomization   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 442 participants 440 participants 882 participants
Moderate 129 125 254
Moderate to severe 234 238 472
Severe 79 77 156
[1]
Measure Description: The index Glasgow Coma Scale (GCS) score is the highest reliable GCS score documented before randomization.The GCS is scored between 3 and 15, 3 being the worst, and 15 the best. A score of 13 or higher correlates with a mild brain injury, 9 to 12 is a moderate injury and 8 or less a severe brain injury.
1.Primary Outcome
Title Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE)
Hide Description A measure of functional recovery: A GOS-E score of 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery. Favorable outcome was defined via stratified dichotomy based on the severity of the initial injury. For subjects with a severe injury, a GOS-E of 3 or higher were considered to be a favorable outcome; for subjects with moderate-to-severe injury, a GOS-E of 5 or higher was considered to be a favorable outcome; for subjects with a moderate injury, a GOS-E of 7 or higher was considered to be a favorable outcome.
Time Frame 6 months post randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was conducted according to intention to treat.
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Favorable Outcome 213 232
Unfavorable 201 184
Missing Data 28 24
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments Test of null hypothesis (equal proportions of subjects with favorable outcome in progesterone and placebo arms) versus alternative hypothesis (unequal proportions of subjects with favorable outcome in progesterone and placebo arms). Standard multiple imputation methods are used to account for missing data. The primary outcome measure is based on the stratified dichotomy approach.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.35
Comments [Not Specified]
Method Regression, Generalized linear
Comments Adjusting for injury severity, sex, and age. the binomial distribution with the log link is used to estimate treatment effect as relative risk.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.85 to 1.06
Estimation Comments A risk ratio (equivalent to the relative risk) of less than 1.00 indicating fewer favorable outcomes in the progesterone group than in the placebo group.
2.Secondary Outcome
Title Mortality
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 83 69
Subjects without events 359 371
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments The Cox proportional hazards model is used to compare these curves after adjustment for age, sex and injury severity.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.86 to 1.63
Estimation Comments A hazard ratio of more than 1.00 indicating higher hazard of death from the progesterone group than in the placebo group.
3.Secondary Outcome
Title Disability Rating Scale
Hide Description A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.9  (4.6) 3.3  (5.1)
4.Secondary Outcome
Title Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis
Hide Description Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 76 25
Subjects without events 366 415
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Progesterone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 3.03
Confidence Interval (2-Sided) 95%
1.96 to 4.66
Estimation Comments A risk ratio (equivalent to the relative risk) of more than 1.00 indicating more events in the progesterone group than in the placebo group.
5.Secondary Outcome
Title Potentially Associated Adverse Events: Pulmonary Embolism
Hide Description Pulmonary embolism - Events were defined based on either positive chest computed tomography (CT) scanning or ventilation/perfusion lung scan (V/Q).
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 10 13
Subjects without events 432 427
6.Secondary Outcome
Title Potentially Associated Adverse Events: Acute Ischemic Stroke
Hide Description Acute ischemic stroke - Events were defined based on either positive computed tomography (CT) scanning, magnetic resonance imaging (MRI), or neurologist diagnosis of cerebrovascular accident (CVA)
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 6 13
Subjects without events 436 427
7.Secondary Outcome
Title Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT)
Hide Description DVT - Events were defined based on a positive Doppler ultrasound exam
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 50 40
Subjects without events 392 400
8.Secondary Outcome
Title Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level
Hide Description Unexplained increased liver enzymes (e.g. not due to liver injury ) - Events were defined based on aspartate transaminase (AST) and alanine transaminase (ALT) levels > 500 U/L and/or total bilirubin levels > 2.0 mg/dL.
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 18 14
Subjects without events 424 426
9.Secondary Outcome
Title Potentially Associated Adverse Events: Sepsis
Hide Description Sepsis - Events must have met Centers for Disease Control and Prevention (CDC) definition of sepsis. The definition includes that a patient ≤1 year of age has at least 1 of the following clinical signs or symptoms with no other recognized cause: fever (>38°C rectal), hypothermia (<37°C rectal), apnea, or bradycardia, and blood culture not done or no organisms detected in blood and no apparent infection at another site and physician institutes treatment for sepsis.
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 9 9
Subjects without events 433 431
10.Secondary Outcome
Title Potentially Associated Adverse Events: Pneumonia
Hide Description Events must have met Centers for Disease Control and Prevention (CDC) definition of pneumonia. There are three specific types of pneumonia: clinically defined pneumonia, pneumonia with specific laboratory findings, and pneumonia in immunocompromised patients. There are specific algorithms to identify each pneumonia, which include x-ray findings, fever with no other cause, leukopenia or leukocytosis, altered mental status with no other cause (adults >70 years old), new onset of purulent sputum, change in character of sputum, increase respiratory secretions, increase suctioning requirements, new onset or worsening cough, dyspnea, tachypnea, rales, bronchial breath sounds, or worsening gas exchange, increased oxygen requirements, or increased ventilator demand). Also, labs can identify pneumonia such as positive growth in blood culture, positive Gram stain, and histopathologic exam evidence.
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 142 140
Subjects without events 300 300
11.Secondary Outcome
Title Potentially Associated Adverse Events: Central Nervous System (CNS) Infection
Hide Description CNS infection - Events must have met Centers for Disease Control and Prevention (CDC) definition of CNS infection. The definition includes intracranial infection, Meningitis, ventriculitis, and spinal abscess without meningitis.
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 5 3
Subjects without events 437 437
12.Secondary Outcome
Title Potentially Associated Adverse Events: Myocardial Infarction (MI)
Hide Description Myocardial infarction - Events were defined based on serial cardiac enzyme elevation consistent with MI and/or new ST elevation on electrocardiogram (ECG) consistent with MI. Potentially associated adverse events (those events which are included as outcome measures) were specifically defined per the protocol, and the classification of an event as a PAAE was determined by the site. The reported name of the associated event, however, was subject to clinical judgement and case details; these were then further coded by the Principal Investigator. Since these data points do not share the same definition, there is no reason to expect perfect concordance. (For example, the potentially associated adverse event of myocardial infarction may include MedDRA codes other than myocardial infarction.)
Time Frame within 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 442 440
Measure Type: Number
Unit of Measure: participants
Subjects with events 5 5
Subjects without events 437 435
Time Frame Within 6 month after the enrollment.
Adverse Event Reporting Description Preferred terms from the MedDRA vocabulary were assigned by investigators for AE names that did not map to lowest level terms and for those where multiple terms mapped to clinically equivalent events.
 
Arm/Group Title Progesterone Placebo
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Progesterone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Progesterone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   246/442 (55.66%)      251/440 (57.05%)    
Blood and lymphatic system disorders     
Anemia *  0/442 (0.00%)  0 1/440 (0.23%)  2
Coagulopathy *  1/442 (0.23%)  1 0/440 (0.00%)  0
Disseminated intravascular coagulation *  2/442 (0.45%)  2 1/440 (0.23%)  1
Cardiac disorders     
Atrial fibrillation *  1/442 (0.23%)  1 3/440 (0.68%)  3
Atrial flutter *  0/442 (0.00%)  0 1/440 (0.23%)  1
Bradycardia *  1/442 (0.23%)  1 1/440 (0.23%)  1
Cardiac arrest *  11/442 (2.49%)  11 7/440 (1.59%)  7
Cardiac failure congestive *  0/442 (0.00%)  0 1/440 (0.23%)  2
Myocardial infarction *  2/442 (0.45%)  2 2/440 (0.45%)  2
Pericardial effusion *  1/442 (0.23%)  1 0/440 (0.00%)  0
Supraventricular tachycardia *  1/442 (0.23%)  1 4/440 (0.91%)  4
Tachycardia *  1/442 (0.23%)  1 0/440 (0.00%)  0
Ear and labyrinth disorders     
Hypoacusis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Vestibular disorder *  1/442 (0.23%)  1 0/440 (0.00%)  0
Endocrine disorders     
Diabetes insipidus *  3/442 (0.68%)  3 0/440 (0.00%)  0
Eye disorders     
Blindness *  0/442 (0.00%)  0 1/440 (0.23%)  1
Ulcerative keratitis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Gastrointestinal disorders     
Abdominal compartment syndrome *  1/442 (0.23%)  1 1/440 (0.23%)  1
Ascites *  1/442 (0.23%)  1 0/440 (0.00%)  0
Colitis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Diarrhoea *  1/442 (0.23%)  1 2/440 (0.45%)  2
Dysphagia *  1/442 (0.23%)  1 0/440 (0.00%)  0
Gastrointestinal hemorrhage *  3/442 (0.68%)  3 3/440 (0.68%)  3
Gastrointestinal perforation *  1/442 (0.23%)  1 1/440 (0.23%)  1
Ileus *  0/442 (0.00%)  0 2/440 (0.45%)  2
Pancreatitis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Pneumoperitoneum *  1/442 (0.23%)  1 0/440 (0.00%)  0
Small intestinal obstruction *  1/442 (0.23%)  1 0/440 (0.00%)  0
Volvulus *  0/442 (0.00%)  0 1/440 (0.23%)  1
Vomiting *  0/442 (0.00%)  0 1/440 (0.23%)  1
General disorders     
Adverse drug reaction *  0/442 (0.00%)  0 2/440 (0.45%)  2
Chest pain *  1/442 (0.23%)  1 2/440 (0.45%)  2
Device occlusion *  1/442 (0.23%)  1 0/440 (0.00%)  0
Infusion site erythema *  1/442 (0.23%)  1 0/440 (0.00%)  0
Pyrexia *  1/442 (0.23%)  1 0/440 (0.00%)  0
Systemic inflammatory response syndrome *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hepatobiliary disorders     
Biloma *  0/442 (0.00%)  0 1/440 (0.23%)  2
Cholecystitis *  0/442 (0.00%)  0 2/440 (0.45%)  2
Cholelithiasis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Portal vein thrombosis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Infections and infestations     
Abdominal abscess *  0/442 (0.00%)  0 2/440 (0.45%)  2
Bacteremia *  7/442 (1.58%)  7 13/440 (2.95%)  13
Cellulitis *  1/442 (0.23%)  1 2/440 (0.45%)  2
Central nervous system infection *  5/442 (1.13%)  6 5/440 (1.14%)  5
Empyema *  1/442 (0.23%)  1 1/440 (0.23%)  1
Parotitis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Perirectal abscess *  1/442 (0.23%)  1 0/440 (0.00%)  0
Peritonitis *  0/442 (0.00%)  0 3/440 (0.68%)  3
Pneumonia *  106/442 (23.98%)  115 113/440 (25.68%)  125
Sepsis *  8/442 (1.81%)  8 9/440 (2.05%)  9
Sinusitis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Subcutaneous abscess *  0/442 (0.00%)  0 2/440 (0.45%)  2
Tracheobronchitis *  2/442 (0.45%)  2 4/440 (0.91%)  4
Tracheostomy infection *  1/442 (0.23%)  1 0/440 (0.00%)  0
Urinary tract infection *  6/442 (1.36%)  6 3/440 (0.68%)  3
Wound infection *  5/442 (1.13%)  5 0/440 (0.00%)  0
Injury, poisoning and procedural complications     
Brain herniation *  5/442 (1.13%)  5 8/440 (1.82%)  8
Extradural hematoma *  2/442 (0.45%)  2 4/440 (0.91%)  4
Fall *  1/442 (0.23%)  1 0/440 (0.00%)  0
Fracture *  0/442 (0.00%)  0 4/440 (0.91%)  5
Gun shot wound *  0/442 (0.00%)  0 2/440 (0.45%)  2
Procedural complication *  3/442 (0.68%)  3 3/440 (0.68%)  3
Shunt malfunction *  3/442 (0.68%)  3 2/440 (0.45%)  2
Subdural hemorrhage *  6/442 (1.36%)  7 4/440 (0.91%)  4
Urethral injury *  0/442 (0.00%)  0 1/440 (0.23%)  1
Vascular pseudoaneurysm *  0/442 (0.00%)  0 1/440 (0.23%)  1
Wound dehiscence *  0/442 (0.00%)  0 2/440 (0.45%)  2
Investigations     
Bacterial test positive *  4/442 (0.90%)  4 4/440 (0.91%)  5
Blood bilirubin increased *  4/442 (0.90%)  4 3/440 (0.68%)  3
Cardiac enzymes increased *  2/442 (0.45%)  2 2/440 (0.45%)  2
Electrocardiogram ST segment elevation *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hepatic enzyme increased *  1/442 (0.23%)  1 0/440 (0.00%)  0
International normalised ratio increased *  0/442 (0.00%)  0 1/440 (0.23%)  1
Lipase increased *  1/442 (0.23%)  1 0/440 (0.00%)  0
Metabolism and nutrition disorders     
Cerebral salt-wasting syndrome *  1/442 (0.23%)  1 0/440 (0.00%)  0
Failure to thrive *  1/442 (0.23%)  1 1/440 (0.23%)  1
Hypercalcemia *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hyperkalemia *  2/442 (0.45%)  2 1/440 (0.23%)  1
Hypernatremia *  1/442 (0.23%)  1 2/440 (0.45%)  2
Hypocalcemia *  1/442 (0.23%)  1 2/440 (0.45%)  2
Hypoglycemia *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hypokalemia *  1/442 (0.23%)  1 5/440 (1.14%)  5
Hyponatremia *  2/442 (0.45%)  2 2/440 (0.45%)  2
Hypophosphatemia *  3/442 (0.68%)  3 7/440 (1.59%)  7
Hypovolemia *  2/442 (0.45%)  2 0/440 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Compartment syndrome *  1/442 (0.23%)  1 0/440 (0.00%)  0
Muscular weakness *  1/442 (0.23%)  1 0/440 (0.00%)  0
Musculoskeletal pain *  1/442 (0.23%)  1 0/440 (0.00%)  0
Osteonecrosis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Rhabdomyolysis *  4/442 (0.90%)  4 0/440 (0.00%)  0
Soft tissue necrosis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Spondylolisthesis *  1/442 (0.23%)  1 1/440 (0.23%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cerebral hygroma *  3/442 (0.68%)  3 1/440 (0.23%)  1
Neoplasm malignant *  2/442 (0.45%)  2 1/440 (0.23%)  1
Nervous system disorders     
Autonomic nervous system imbalance *  0/442 (0.00%)  0 2/440 (0.45%)  2
Brain edema *  22/442 (4.98%)  22 16/440 (3.64%)  17
Brain injury *  10/442 (2.26%)  10 8/440 (1.82%)  8
Cerebral hemorrhage *  8/442 (1.81%)  8 4/440 (0.91%)  4
Cerebral venous thrombosis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Cerebrospinal fluid rhinorrhea *  1/442 (0.23%)  1 1/440 (0.23%)  1
Chorea *  1/442 (0.23%)  1 0/440 (0.00%)  0
Convulsion *  6/442 (1.36%)  6 8/440 (1.82%)  9
Headache *  1/442 (0.23%)  1 0/440 (0.00%)  0
Hemorrhage intracranial *  6/442 (1.36%)  6 12/440 (2.73%)  12
Hepatic encephalopathy *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hydrocephalus *  12/442 (2.71%)  12 8/440 (1.82%)  8
Intracranial hypotension *  1/442 (0.23%)  1 0/440 (0.00%)  0
Ischemic stroke *  5/442 (1.13%)  5 13/440 (2.95%)  13
Neurological decompensation *  7/442 (1.58%)  7 11/440 (2.50%)  11
Paresis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Status epilepticus *  3/442 (0.68%)  3 0/440 (0.00%)  0
Subarachnoid hemorrhage *  1/442 (0.23%)  1 3/440 (0.68%)  3
Vocal cord paresis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Psychiatric disorders     
Affective disorder *  3/442 (0.68%)  3 3/440 (0.68%)  4
Alcohol withdrawal syndrome *  0/442 (0.00%)  0 2/440 (0.45%)  2
Impulsive behaviour *  0/442 (0.00%)  0 1/440 (0.23%)  1
Mental status changes *  8/442 (1.81%)  9 7/440 (1.59%)  7
Personality change *  1/442 (0.23%)  1 1/440 (0.23%)  1
Suicide attempt *  1/442 (0.23%)  1 1/440 (0.23%)  1
Withdrawal syndrome *  0/442 (0.00%)  0 1/440 (0.23%)  1
Renal and urinary disorders     
Renal failure *  9/442 (2.04%)  9 7/440 (1.59%)  7
Reproductive system and breast disorders     
Pelvic pain *  0/442 (0.00%)  0 1/440 (0.23%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome *  4/442 (0.90%)  5 8/440 (1.82%)  8
Aspiration *  2/442 (0.45%)  2 2/440 (0.45%)  2
Atelectasis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Bronchial secretion retention *  1/442 (0.23%)  1 3/440 (0.68%)  3
Hemothorax *  2/442 (0.45%)  2 3/440 (0.68%)  3
Hypoxia *  2/442 (0.45%)  2 2/440 (0.45%)  2
Pleural effusion *  2/442 (0.45%)  2 3/440 (0.68%)  3
Pneumothorax *  12/442 (2.71%)  13 6/440 (1.36%)  6
Pulmonary edema *  0/442 (0.00%)  0 2/440 (0.45%)  2
Pulmonary embolism *  11/442 (2.49%)  11 11/440 (2.50%)  11
Respiratory distress *  4/442 (0.90%)  4 11/440 (2.50%)  11
Respiratory failure *  22/442 (4.98%)  22 16/440 (3.64%)  16
Stridor *  3/442 (0.68%)  3 0/440 (0.00%)  0
Tracheal stenosis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Skin and subcutaneous tissue disorders     
Decubitus ulcer *  1/442 (0.23%)  1 1/440 (0.23%)  1
Subcutaneous emphysema *  1/442 (0.23%)  1 0/440 (0.00%)  0
Social circumstances     
Respite care *  0/442 (0.00%)  0 1/440 (0.23%)  1
Surgical and medical procedures     
Surgery *  2/442 (0.45%)  2 2/440 (0.45%)  2
Vascular disorders     
Aortic aneurysm rupture *  1/442 (0.23%)  1 0/440 (0.00%)  0
Artery dissection *  1/442 (0.23%)  1 0/440 (0.00%)  0
Circulatory collapse *  2/442 (0.45%)  2 3/440 (0.68%)  3
Deep vein thrombosis *  33/442 (7.47%)  36 27/440 (6.14%)  27
Hemorrhage *  2/442 (0.45%)  2 0/440 (0.00%)  0
Hypertension *  1/442 (0.23%)  1 0/440 (0.00%)  0
Phlebitis *  12/442 (2.71%)  12 5/440 (1.14%)  5
Thrombosis *  1/442 (0.23%)  1 0/440 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Progesterone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   332/442 (75.11%)      330/440 (75.00%)    
Blood and lymphatic system disorders     
Anemia *  8/442 (1.81%)  9 11/440 (2.50%)  12
Coagulopathy *  3/442 (0.68%)  3 1/440 (0.23%)  1
Leukocytosis *  12/442 (2.71%)  13 6/440 (1.36%)  6
Thrombocytopenia *  4/442 (0.90%)  5 7/440 (1.59%)  7
Thrombocytosis *  0/442 (0.00%)  0 3/440 (0.68%)  3
Cardiac disorders     
Atrial fibrillation *  3/442 (0.68%)  3 4/440 (0.91%)  4
Bradycardia *  5/442 (1.13%)  6 10/440 (2.27%)  11
Extrasystoles *  2/442 (0.45%)  2 1/440 (0.23%)  1
Myocardial infarction *  2/442 (0.45%)  2 2/440 (0.45%)  2
Supraventricular tachycardia *  4/442 (0.90%)  4 2/440 (0.45%)  2
Tachycardia *  13/442 (2.94%)  13 8/440 (1.82%)  11
Ventricular tachycardia *  2/442 (0.45%)  2 0/440 (0.00%)  0
Ear and labyrinth disorders     
Hypoacusis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Endocrine disorders     
Adrenal insufficiency *  0/442 (0.00%)  0 1/440 (0.23%)  1
Diabetes insipidus *  3/442 (0.68%)  3 2/440 (0.45%)  2
Eye disorders     
Conjunctival oedema *  0/442 (0.00%)  0 1/440 (0.23%)  1
Diplopia *  0/442 (0.00%)  0 1/440 (0.23%)  1
Eye pain *  0/442 (0.00%)  0 1/440 (0.23%)  1
Mydriasis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Vision blurred *  0/442 (0.00%)  0 1/440 (0.23%)  1
Gastrointestinal disorders     
Constipation *  3/442 (0.68%)  3 5/440 (1.14%)  5
Diarrhoea *  2/442 (0.45%)  2 1/440 (0.23%)  1
Gastrointestinal hemorrhage *  3/442 (0.68%)  3 2/440 (0.45%)  2
Nausea *  3/442 (0.68%)  3 1/440 (0.23%)  1
Vomiting *  6/442 (1.36%)  7 3/440 (0.68%)  3
General disorders     
Adverse drug reaction *  1/442 (0.23%)  1 1/440 (0.23%)  1
Catheter site hemorrhage *  1/442 (0.23%)  1 0/440 (0.00%)  0
Chest pain *  0/442 (0.00%)  0 1/440 (0.23%)  1
Chills *  1/442 (0.23%)  1 1/440 (0.23%)  1
Edema peripheral *  1/442 (0.23%)  1 0/440 (0.00%)  0
Infusion site edema *  12/442 (2.71%)  14 4/440 (0.91%)  5
Infusion site erythema *  7/442 (1.58%)  7 3/440 (0.68%)  3
Infusion site extravasation *  15/442 (3.39%)  16 9/440 (2.05%)  10
Infusion site pain *  1/442 (0.23%)  1 1/440 (0.23%)  1
Local swelling *  1/442 (0.23%)  1 0/440 (0.00%)  0
Pyrexia *  0/442 (0.00%)  0 1/440 (0.23%)  1
Systemic inflammatory response syndrome *  1/442 (0.23%)  1 0/440 (0.00%)  0
Hepatobiliary disorders     
Hepatitis alcoholic *  0/442 (0.00%)  0 1/440 (0.23%)  1
Immune system disorders     
Hypersensitivity *  1/442 (0.23%)  1 0/440 (0.00%)  0
Infections and infestations     
Abdominal abscess *  0/442 (0.00%)  0 1/440 (0.23%)  1
Bacteremia *  2/442 (0.45%)  2 2/440 (0.45%)  2
Bronchitis *  2/442 (0.45%)  2 2/440 (0.45%)  2
Candidiasis *  1/442 (0.23%)  1 1/440 (0.23%)  1
Cellulitis *  4/442 (0.90%)  4 2/440 (0.45%)  2
Central nervous system infection *  1/442 (0.23%)  1 2/440 (0.45%)  2
Device related infection *  1/442 (0.23%)  1 0/440 (0.00%)  0
Fungal infection *  1/442 (0.23%)  1 0/440 (0.00%)  0
Mastoiditis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Pneumonia *  53/442 (11.99%)  54 49/440 (11.14%)  50
Respiratory tract infection *  4/442 (0.90%)  4 1/440 (0.23%)  1
Sepsis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Sinusitis *  1/442 (0.23%)  1 1/440 (0.23%)  1
Subcutaneous abscess *  0/442 (0.00%)  0 1/440 (0.23%)  1
Tracheobronchitis *  1/442 (0.23%)  1 2/440 (0.45%)  2
Urinary tract infection *  14/442 (3.17%)  14 15/440 (3.41%)  15
Vaginal infection *  3/442 (0.68%)  3 2/440 (0.45%)  2
Wound infection *  1/442 (0.23%)  1 2/440 (0.45%)  2
Injury, poisoning and procedural complications     
Endotracheal intubation complication *  1/442 (0.23%)  1 0/440 (0.00%)  0
Fall *  1/442 (0.23%)  1 2/440 (0.45%)  2
Heart injury *  1/442 (0.23%)  1 1/440 (0.23%)  1
Procedural complication *  3/442 (0.68%)  3 1/440 (0.23%)  1
Subdural hemorrhage *  0/442 (0.00%)  0 3/440 (0.68%)  3
Transfusion reaction *  0/442 (0.00%)  0 1/440 (0.23%)  1
Investigations     
Acid base balance abnormal *  0/442 (0.00%)  0 1/440 (0.23%)  1
Activated partial thromboplastin time prolonged *  2/442 (0.45%)  2 0/440 (0.00%)  0
Amylase increased *  2/442 (0.45%)  2 0/440 (0.00%)  0
Bacterial test positive *  6/442 (1.36%)  6 2/440 (0.45%)  2
Blood albumin decreased *  1/442 (0.23%)  1 2/440 (0.45%)  3
Blood bicarbonate abnormal *  1/442 (0.23%)  1 0/440 (0.00%)  0
Blood bilirubin increased *  12/442 (2.71%)  12 8/440 (1.82%)  8
Blood calcium abnormal *  0/442 (0.00%)  0 1/440 (0.23%)  1
Blood creatine phosphokinase increased *  3/442 (0.68%)  3 2/440 (0.45%)  2
Blood fibrinogen increased *  1/442 (0.23%)  1 0/440 (0.00%)  0
Blood folate decreased *  0/442 (0.00%)  0 1/440 (0.23%)  1
Blood lactic acid increased *  7/442 (1.58%)  8 1/440 (0.23%)  1
Blood magnesium abnormal *  0/442 (0.00%)  0 3/440 (0.68%)  3
Blood osmolarity increased *  4/442 (0.90%)  4 3/440 (0.68%)  3
Blood phosphorus abnormal *  0/442 (0.00%)  0 1/440 (0.23%)  1
Blood potassium abnormal *  2/442 (0.45%)  2 4/440 (0.91%)  4
Blood sodium abnormal *  2/442 (0.45%)  2 2/440 (0.45%)  2
Blood urea increased *  2/442 (0.45%)  2 0/440 (0.00%)  0
Cardiac enzymes increased *  1/442 (0.23%)  1 2/440 (0.45%)  2
Drug level below therapeutic *  0/442 (0.00%)  0 1/440 (0.23%)  1
Electrocardiogram ST segment elevation *  2/442 (0.45%)  2 0/440 (0.00%)  0
Full blood count abnormal *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hepatic enzyme increased *  8/442 (1.81%)  8 8/440 (1.82%)  8
International normalised ratio increased *  4/442 (0.90%)  4 1/440 (0.23%)  1
Myoglobin blood increased *  1/442 (0.23%)  1 1/440 (0.23%)  1
Prealbumin decreased *  1/442 (0.23%)  1 0/440 (0.00%)  0
White blood cell count abnormal *  2/442 (0.45%)  2 4/440 (0.91%)  4
Metabolism and nutrition disorders     
Acidosis *  7/442 (1.58%)  7 11/440 (2.50%)  11
Alkalosis *  9/442 (2.04%)  9 8/440 (1.82%)  8
Fluid overload *  4/442 (0.90%)  4 4/440 (0.91%)  4
Hyperchloremia *  7/442 (1.58%)  9 9/440 (2.05%)  9
Hyperglycemia *  6/442 (1.36%)  6 4/440 (0.91%)  4
Hyperkalemia *  8/442 (1.81%)  8 3/440 (0.68%)  3
Hyperlipidemia *  1/442 (0.23%)  1 0/440 (0.00%)  0
Hypermagnesemia *  5/442 (1.13%)  6 5/440 (1.14%)  5
Hypernatremia *  21/442 (4.75%)  21 29/440 (6.59%)  29
Hyperphosphatemia *  6/442 (1.36%)  6 2/440 (0.45%)  2
Hypocalcemia *  78/442 (17.65%)  83 101/440 (22.95%)  110
Hypochloremia *  2/442 (0.45%)  2 1/440 (0.23%)  1
Hypoglycemia *  1/442 (0.23%)  1 1/440 (0.23%)  1
Hypokalemia *  72/442 (16.29%)  83 111/440 (25.23%)  129
Hypomagnesemia *  90/442 (20.36%)  101 94/440 (21.36%)  100
Hyponatremia *  29/442 (6.56%)  30 20/440 (4.55%)  21
Hypophosphatemia *  134/442 (30.32%)  145 134/440 (30.45%)  146
Hypovolemia *  1/442 (0.23%)  1 2/440 (0.45%)  2
Propofol infusion syndrome *  0/442 (0.00%)  0 1/440 (0.23%)  1
Musculoskeletal and connective tissue disorders     
Compartment syndrome *  1/442 (0.23%)  1 0/440 (0.00%)  0
Muscular weakness *  0/442 (0.00%)  0 1/440 (0.23%)  1
Musculoskeletal pain *  1/442 (0.23%)  1 0/440 (0.00%)  0
Rhabdomyolysis *  3/442 (0.68%)  3 3/440 (0.68%)  3
Soft tissue necrosis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Nervous system disorders     
Autonomic nervous system imbalance *  2/442 (0.45%)  2 4/440 (0.91%)  4
Brain edema *  0/442 (0.00%)  0 3/440 (0.68%)  3
Cerebral hemorrhage *  0/442 (0.00%)  0 1/440 (0.23%)  1
Cerebral venous thrombosis *  1/442 (0.23%)  1 0/440 (0.00%)  0
Cerebrospinal fluid rhinorrhea *  0/442 (0.00%)  0 1/440 (0.23%)  1
Convulsion *  5/442 (1.13%)  5 9/440 (2.05%)  9
Dizziness *  0/442 (0.00%)  0 1/440 (0.23%)  1
Headache *  3/442 (0.68%)  3 4/440 (0.91%)  4
Hemorrhage intracranial *  3/442 (0.68%)  3 4/440 (0.91%)  4
Ischemic stroke *  2/442 (0.45%)  2 0/440 (0.00%)  0
Neurological decompensation *  1/442 (0.23%)  1 0/440 (0.00%)  0
Paresis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Tremor *  0/442 (0.00%)  0 1/440 (0.23%)  1
VIth nerve disorder *  0/442 (0.00%)  0 1/440 (0.23%)  1
Psychiatric disorders     
Affective disorder *  1/442 (0.23%)  1 2/440 (0.45%)  2
Alcohol withdrawal syndrome *  0/442 (0.00%)  0 1/440 (0.23%)  1
Impulsive behaviour *  0/442 (0.00%)  0 1/440 (0.23%)  1
Mental status changes *  10/442 (2.26%)  11 10/440 (2.27%)  10
Withdrawal syndrome *  0/442 (0.00%)  0 1/440 (0.23%)  1
Renal and urinary disorders     
Hematuria *  0/442 (0.00%)  0 1/440 (0.23%)  1
Nephrolithiasis *  0/442 (0.00%)  0 1/440 (0.23%)  1
Renal failure *  3/442 (0.68%)  3 7/440 (1.59%)  7
Urinary retention *  1/442 (0.23%)  1 2/440 (0.45%)  2
Respiratory, thoracic and mediastinal disorders     
Aspiration *  2/442 (0.45%)  2 0/440 (0.00%)  0
Atelectasis *  8/442 (1.81%)  8 4/440 (0.91%)  4
Epistaxis *  0/442 (0.00%)  0 2/440 (0.45%)  2
Hemothorax *  1/442 (0.23%)  1 1/440 (0.23%)  1
Hiccups *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hypocapnia *  0/442 (0.00%)  0 1/440 (0.23%)  1
Hypoxia *  2/442 (0.45%)  2 2/440 (0.45%)  2
Lung infiltration *  2/442 (0.45%)  2 4/440 (0.91%)  4
Pleural effusion *  4/442 (0.90%)  4 5/440 (1.14%)  5
Pneumomediastinum *  1/442 (0.23%)  1 2/440 (0.45%)  2
Pneumothorax *  9/442 (2.04%)  10 22/440 (5.00%)  24
Pulmonary edema *  4/442 (0.90%)  4 6/440 (1.36%)  6
Pulmonary embolism *  0/442 (0.00%)  0 2/440 (0.45%)  2
Respiratory distress *  1/442 (0.23%)  1 0/440 (0.00%)  0
Respiratory failure *  0/442 (0.00%)  0 2/440 (0.45%)  2
Tachypnoea *  0/442 (0.00%)  0 1/440 (0.23%)  1
Skin and subcutaneous tissue disorders     
Angioedema *  0/442 (0.00%)  0 1/440 (0.23%)  1
Decubitus ulcer *  1/442 (0.23%)  1 0/440 (0.00%)  0
Erythema *  1/442 (0.23%)  1 0/440 (0.00%)  0
Pruritus *  3/442 (0.68%)  3 0/440 (0.00%)  0
Rash *  6/442 (1.36%)  6 6/440 (1.36%)  6
Subcutaneous emphysema *  0/442 (0.00%)  0 2/440 (0.45%)  2
Vascular disorders     
Artery dissection *  0/442 (0.00%)  0 2/440 (0.45%)  2
Deep vein thrombosis *  20/442 (4.52%)  22 13/440 (2.95%)  13
Hemorrhage *  1/442 (0.23%)  1 0/440 (0.00%)  0
Hypertension *  2/442 (0.45%)  3 2/440 (0.45%)  2
Hypotension *  0/442 (0.00%)  0 1/440 (0.23%)  2
Peripheral ischemia *  0/442 (0.00%)  0 1/440 (0.23%)  1
Phlebitis *  74/442 (16.74%)  89 24/440 (5.45%)  27
Thrombosis *  2/442 (0.45%)  3 2/440 (0.45%)  2
*
Indicates events were collected by non-systematic assessment
The trial was stopped early for futility with respect to the primary outcome.
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: David W. Wright, Associate Professor, Department of Emergency Medicine, Emory University
Organization: Emergency Neurosciences, Emergency Medicine, Emory University
Phone: 404-778-1709
Responsible Party: David Wright, Emory University
ClinicalTrials.gov Identifier: NCT00822900     History of Changes
Other Study ID Numbers: IRB00014409
1RO1 NS062778-01
First Submitted: January 14, 2009
First Posted: January 15, 2009
Results First Submitted: April 1, 2015
Results First Posted: July 3, 2015
Last Update Posted: January 20, 2016