ProTECT: Progesterone for the Treatment of Traumatic Brain Injury III
Sponsor
David Wright (Other)
Overall Status
Terminated
CT.gov ID
NCT00822900
Collaborator
Medical University of South Carolina (Other), Neurological Emergencies Treatment Trials Network (NETT) (Other)
882
36
2
52
24.5
0.5
Study Details
Study Description
Brief Summary
The ProTECT study will determine if intravenous (IV) progesterone (started within 4 hours of injury and given for a total of 96 hours), is more effective than placebo for treating victims of moderate to severe acute traumatic brain injury.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
882 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Phase 3 Clinical Trial to Determine if Progesterone Along With Standard Medical Care for Brain Injury is More Effective at Limiting the Amount of Damage Cause by a Traumatic Brain Injury Than Standard Medical Care Alone.
Study Start Date
:
Mar 1, 2010
Actual Primary Completion Date
:
May 1, 2014
Actual Study Completion Date
:
Jul 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Progesterone Following a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (progesterone) will be administered as a continuous intravenous infusion at 0.5 mg/kg/hr for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table will be used by the on-sight pharmacy to mix the correct dose for a 10 cc/hour continuous infusion over the 72 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The progesterone will be combined with a 20% Intralipid mixture for infusion. |
Drug: Progesterone
Following a one hour loading dose of 0.714 mg/kg per infusion pump through a dedicated IV line, the study drug (progesterone or placebo) will be administered as a continuous intravenous infusion at 0.5 mg/kg/hr for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table will be used by the on-sight pharmacy to mix the correct dose for a 10 cc/hour continuous infusion over the 71 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The progesterone/placebo will be combined with a 20% Intralipid mixture for infusion.
|
| Placebo Comparator: Placebo Placebo stock solution was the ethanol diluent required for dissolving progesterone. The volume of placebo to be mixed with intralipid was based on the same mg/kg/hr volume that would be required if PROG had been in the vial. Using an infusion pump through a dedicated IV line - a one hour "loading dose" of placebo plus intralipid was administered as a continuous intravenous infusion for 71 hours, then tapered over an additional 24 hours. To simplify the infusion protocol, a weight based dosing table was used by the on-sight pharmacy to mix the correct "dose" for a 10 cc/hour continuous infusion over the 72 hour steady state period followed by three additional 8-hour decrements (7.5 cc/hr-5.0 cc/hr-2.5 cc/hr) to zero, for a total treatment duration of 96 hour. The placebo will be combined with a 20% Intralipid mixture for infusion. |
Drug: Placebo
Placebo stock solution is the ethanol diluent required for dissolving progesterone. The volume of placebo to be mixed with intralipid is based on the mg/kg/hr volume. Using an infusion pump through a dedicated IV line - a one hour "loading dose" of placebo plus intralipid is administered as a continuous intravenous infusion for 71 hours, then tapered over an additional 24 hours.
|
Outcome Measures
Primary Outcome Measures
- Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) [6 months post randomization]
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.
Secondary Outcome Measures
- Mortality [6 months]
- Disability Rating Scale [6 months]
A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29.
- Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis [within 6 months]
Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV)
- Potentially Associated Adverse Events: Pulmonary Embolism [within 6 months]
Pulmonary embolism - Events were defined based on either positive chest computed tomography (CT) scanning or ventilation/perfusion lung scan (V/Q).
- Potentially Associated Adverse Events: Acute Ischemic Stroke [within 6 months]
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)
- Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT) [within 6 months]
DVT - Events were defined based on a positive Doppler ultrasound exam
- Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level [within 6 months]
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.
- Potentially Associated Adverse Events: Sepsis [within 6 months]
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.
- Potentially Associated Adverse Events: Pneumonia [within 6 months]
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.
- Potentially Associated Adverse Events: Central Nervous System (CNS) Infection [within 6 months]
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.
- Potentially Associated Adverse Events: Myocardial Infarction (MI) [within 6 months]
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.)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Moderate to severe brain injury (GCS 12-4)
-
Age 18 years or older
-
Blunt, closed head injury
-
Study drug initiated within 4 hours of injury
Exclusion Criteria:
-
Non-Survivable injury
-
Bilateral dilated unresponsive pupils
-
Severe intoxication (ETOH > 250 mg %)
-
Spinal cord injury with neurological deficits
-
Inability to perform activities of daily living prior to injury
-
Cardiopulmonary arrest
-
Status epilepticus on arrival
-
Systolic blood pressure (SBP) < 90 on arrival or for at least 5 minutes prior to enrollment
-
O2 Sat < 90 on arrival or for at least 5 minutes prior to enrollment
-
Prisoner or ward of state
-
Pregnant
-
Active breast or reproductive organ cancers
-
Known allergy to progesterone or intralipid components (egg yolk)
-
Known history of clotting disorder
-
Active thromboembolic event
-
Concern for inability to follow up at 6 months
-
Anyone listed in the Opt out registry
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Maricopa Integrated Health System | Phoenix | Arizona | United States | 85008 |
| 2 | Banner Good Samaritan | Phoenix | Arizona | United States | |
| 3 | Scottsdale Healthcare | Scottsdale | Arizona | United States | |
| 4 | University of Arizona Medical Center | Tuscon | Arizona | United States | 85724 |
| 5 | Santa Clara Valley Hospital | Palo Alto | California | United States | 94304 |
| 6 | Stanford Medical Center | Palo Alto | California | United States | 94304 |
| 7 | San Francisco General Hospital | San Francisco | California | United States | 94110 |
| 8 | Regional Medical Center-San Jose | San Jose | California | United States | |
| 9 | Grady Memorial Hospital | Atlanta | Georgia | United States | 30303 |
| 10 | University of Kentucky Medical Center | Lexington | Kentucky | United States | 40536 |
| 11 | University of Maryland Shock Trauma | Baltimore | Maryland | United States | 21201 |
| 12 | Detroit Receiving Hospital | Detroit | Michigan | United States | 48202 |
| 13 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 14 | Sinai Grace Hospital | Detroit | Michigan | United States | |
| 15 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 16 | Beaumont Royal Oak Hospital | Royal Oak | Michigan | United States | 48073 |
| 17 | Hennepin County Medical Center | Minneapolis | Minnesota | United States | 55414 |
| 18 | North Memorial Hospital | Robbinsdale | Minnesota | United States | |
| 19 | Regions Hospital | St. Paul | Minnesota | United States | 55101 |
| 20 | St. Johns Mercy Medical Center | St. Louis | Missouri | United States | 63141 |
| 21 | Columbia New York Presbyterian Hospital | New York | New York | United States | 10032 |
| 22 | University Hospital | Cincinnatti | Ohio | United States | 45267 |
| 23 | Oregon Health Sciences University | Portland | Oregon | United States | 97239 |
| 24 | St. Luke's Hospital | Bethlehem | Pennsylvania | United States | 18017 |
| 25 | Geisinger Medical Center | Danville | Pennsylvania | United States | |
| 26 | Penn State Milton S. Hershey Medical Center | Hershey | Pennsylvania | United States | 17033 |
| 27 | Hahnemann University Hospital | Philadelphia | Pennsylvania | United States | 19102 |
| 28 | University of Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19104 |
| 29 | Thomas Jefferson UniversityHospital | Philadelphia | Pennsylvania | United States | 19107 |
| 30 | Temple University Hospital | Philadelphia | Pennsylvania | United States | 19140 |
| 31 | Regional Medical Center/Elvis Presley Memorial Trauma Center (The MED) | Memphis | Tennessee | United States | |
| 32 | Austin/Brackenridge | Austin | Texas | United States | 78752 |
| 33 | Memorial Hermann | Houston | Texas | United States | 77030 |
| 34 | Brooke Army Medical Center | San Antonio | Texas | United States | |
| 35 | Virginia Commonwealth | Richmond | Virginia | United States | 23298 |
| 36 | Froedtert East Hospital | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- David Wright
- Medical University of South Carolina
- Neurological Emergencies Treatment Trials Network (NETT)
Investigators
- Principal Investigator: David W Wright, MD, Emory University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
David Wright,
Principal Investigator,
Emory University
ClinicalTrials.gov Identifier:
NCT00822900
Other Study ID Numbers:
- IRB00014409
- 1RO1 NS062778-01
First Posted:
Jan 15, 2009
Last Update Posted:
Jan 20, 2016
Last Verified:
Dec 1, 2015
Keywords provided by David Wright,
Principal Investigator,
Emory University
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Period Title: Overall Study | ||
| STARTED | 442 | 440 |
| COMPLETED | 334 | 347 |
| NOT COMPLETED | 108 | 93 |
Baseline Characteristics
| Arm/Group Title | Progesterone | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Total of all reporting groups | ||
| Overall Participants | 442 | 440 | 882 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
39
(18)
|
38
(17)
|
39
(18)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
118
26.7%
|
114
25.9%
|
232
26.3%
|
| Male |
324
73.3%
|
326
74.1%
|
650
73.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
61
13.8%
|
64
14.5%
|
125
14.2%
|
| Not Hispanic or Latino |
347
78.5%
|
343
78%
|
690
78.2%
|
| Unknown or Not Reported |
34
7.7%
|
33
7.5%
|
67
7.6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
5
1.1%
|
2
0.5%
|
7
0.8%
|
| Asian |
20
4.5%
|
22
5%
|
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%
|
| Unknown or Not Reported |
13
2.9%
|
13
3%
|
26
2.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
442
100%
|
440
100%
|
882
100%
|
| Index GCS score at randomization (participants) [Number] | |||
| Moderate |
129
29.2%
|
125
28.4%
|
254
28.8%
|
| Moderate to severe |
234
52.9%
|
238
54.1%
|
472
53.5%
|
| Severe |
79
17.9%
|
77
17.5%
|
156
17.7%
|
Outcome Measures
| Title | Favorable Outcome as Determined by the Glasgow Outcome Scale-Extended (GOSE) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary analysis was conducted according to intention to treat. |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Favorable Outcome |
213
48.2%
|
232
52.7%
|
| Unfavorable |
201
45.5%
|
184
41.8%
|
| Missing Data |
28
6.3%
|
24
5.5%
|
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 | ||
| Statistical Test of Hypothesis | p-Value | 0.35 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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. | |
| Title | Mortality |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
83
18.8%
|
69
15.7%
|
| Subjects without events |
359
81.2%
|
371
84.3%
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.19 | |
| Confidence Interval |
(2-Sided) 95% 0.86 to 1.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | A hazard ratio of more than 1.00 indicating higher hazard of death from the progesterone group than in the placebo group. | |
| Title | Disability Rating Scale |
|---|---|
| Description | A measure of functional impairment, with complete recovery scored a 0 and vegetative state scored a 29. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Mean (Standard Deviation) [units on a scale] |
2.9
(4.6)
|
3.3
(5.1)
|
| Title | Potentially Associated Adverse Events: Phlebitis/Thrombophlebitis |
|---|---|
| Description | Phlebitis/Thrombophlebitis (not due to infiltration or misplacement of the IV) |
| Time Frame | within 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
76
17.2%
|
25
5.7%
|
| Subjects without events |
366
82.8%
|
415
94.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Progesterone, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 3.03 | |
| Confidence Interval |
(2-Sided) 95% 1.96 to 4.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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. | |
| Title | Potentially Associated Adverse Events: Pulmonary Embolism |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
10
2.3%
|
13
3%
|
| Subjects without events |
432
97.7%
|
427
97%
|
| Title | Potentially Associated Adverse Events: Acute Ischemic Stroke |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
6
1.4%
|
13
3%
|
| Subjects without events |
436
98.6%
|
427
97%
|
| Title | Potentially Associated Adverse Events: Deep Venous Thrombosis (DVT) |
|---|---|
| Description | DVT - Events were defined based on a positive Doppler ultrasound exam |
| Time Frame | within 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
50
11.3%
|
40
9.1%
|
| Subjects without events |
392
88.7%
|
400
90.9%
|
| Title | Potentially Associated Adverse Events: Unexplained Increased Liver-enzyme Level |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
18
4.1%
|
14
3.2%
|
| Subjects without events |
424
95.9%
|
426
96.8%
|
| Title | Potentially Associated Adverse Events: Sepsis |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
9
2%
|
9
2%
|
| Subjects without events |
433
98%
|
431
98%
|
| Title | Potentially Associated Adverse Events: Pneumonia |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
142
32.1%
|
140
31.8%
|
| Subjects without events |
300
67.9%
|
300
68.2%
|
| Title | Potentially Associated Adverse Events: Central Nervous System (CNS) Infection |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
5
1.1%
|
3
0.7%
|
| Subjects without events |
437
98.9%
|
437
99.3%
|
| Title | Potentially Associated Adverse Events: Myocardial Infarction (MI) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Progesterone | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 442 | 440 |
| Subjects with events |
5
1.1%
|
5
1.1%
|
| Subjects without events |
437
98.9%
|
435
98.9%
|
Adverse Events
| 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 | ||
| Arm/Group Description | ||||
All Cause Mortality |
||||
| Progesterone | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Progesterone | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 246/442 (55.7%) | 251/440 (57%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 0/442 (0%) | 0 | 1/440 (0.2%) | 2 |
| Coagulopathy | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Disseminated intravascular coagulation | 2/442 (0.5%) | 2 | 1/440 (0.2%) | 1 |
| Cardiac disorders | ||||
| Atrial fibrillation | 1/442 (0.2%) | 1 | 3/440 (0.7%) | 3 |
| Atrial flutter | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Bradycardia | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Cardiac arrest | 11/442 (2.5%) | 11 | 7/440 (1.6%) | 7 |
| Cardiac failure congestive | 0/442 (0%) | 0 | 1/440 (0.2%) | 2 |
| Myocardial infarction | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Pericardial effusion | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Supraventricular tachycardia | 1/442 (0.2%) | 1 | 4/440 (0.9%) | 4 |
| Tachycardia | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Hypoacusis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Vestibular disorder | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Endocrine disorders | ||||
| Diabetes insipidus | 3/442 (0.7%) | 3 | 0/440 (0%) | 0 |
| Eye disorders | ||||
| Blindness | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Ulcerative keratitis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal compartment syndrome | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Ascites | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Colitis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Diarrhoea | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Dysphagia | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Gastrointestinal hemorrhage | 3/442 (0.7%) | 3 | 3/440 (0.7%) | 3 |
| Gastrointestinal perforation | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Ileus | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Pancreatitis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Pneumoperitoneum | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Small intestinal obstruction | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Volvulus | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Vomiting | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| General disorders | ||||
| Adverse drug reaction | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Chest pain | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Device occlusion | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Infusion site erythema | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Pyrexia | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Systemic inflammatory response syndrome | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hepatobiliary disorders | ||||
| Biloma | 0/442 (0%) | 0 | 1/440 (0.2%) | 2 |
| Cholecystitis | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Cholelithiasis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Portal vein thrombosis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Infections and infestations | ||||
| Abdominal abscess | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Bacteremia | 7/442 (1.6%) | 7 | 13/440 (3%) | 13 |
| Cellulitis | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Central nervous system infection | 5/442 (1.1%) | 6 | 5/440 (1.1%) | 5 |
| Empyema | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Parotitis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Perirectal abscess | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Peritonitis | 0/442 (0%) | 0 | 3/440 (0.7%) | 3 |
| Pneumonia | 106/442 (24%) | 115 | 113/440 (25.7%) | 125 |
| Sepsis | 8/442 (1.8%) | 8 | 9/440 (2%) | 9 |
| Sinusitis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Subcutaneous abscess | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Tracheobronchitis | 2/442 (0.5%) | 2 | 4/440 (0.9%) | 4 |
| Tracheostomy infection | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Urinary tract infection | 6/442 (1.4%) | 6 | 3/440 (0.7%) | 3 |
| Wound infection | 5/442 (1.1%) | 5 | 0/440 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Brain herniation | 5/442 (1.1%) | 5 | 8/440 (1.8%) | 8 |
| Extradural hematoma | 2/442 (0.5%) | 2 | 4/440 (0.9%) | 4 |
| Fall | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Fracture | 0/442 (0%) | 0 | 4/440 (0.9%) | 5 |
| Gun shot wound | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Procedural complication | 3/442 (0.7%) | 3 | 3/440 (0.7%) | 3 |
| Shunt malfunction | 3/442 (0.7%) | 3 | 2/440 (0.5%) | 2 |
| Subdural hemorrhage | 6/442 (1.4%) | 7 | 4/440 (0.9%) | 4 |
| Urethral injury | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Vascular pseudoaneurysm | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Wound dehiscence | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Investigations | ||||
| Bacterial test positive | 4/442 (0.9%) | 4 | 4/440 (0.9%) | 5 |
| Blood bilirubin increased | 4/442 (0.9%) | 4 | 3/440 (0.7%) | 3 |
| Cardiac enzymes increased | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Electrocardiogram ST segment elevation | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hepatic enzyme increased | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| International normalised ratio increased | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Lipase increased | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Cerebral salt-wasting syndrome | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Failure to thrive | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Hypercalcemia | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hyperkalemia | 2/442 (0.5%) | 2 | 1/440 (0.2%) | 1 |
| Hypernatremia | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Hypocalcemia | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Hypoglycemia | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hypokalemia | 1/442 (0.2%) | 1 | 5/440 (1.1%) | 5 |
| Hyponatremia | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Hypophosphatemia | 3/442 (0.7%) | 3 | 7/440 (1.6%) | 7 |
| Hypovolemia | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Compartment syndrome | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Muscular weakness | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Musculoskeletal pain | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Osteonecrosis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Rhabdomyolysis | 4/442 (0.9%) | 4 | 0/440 (0%) | 0 |
| Soft tissue necrosis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Spondylolisthesis | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cerebral hygroma | 3/442 (0.7%) | 3 | 1/440 (0.2%) | 1 |
| Neoplasm malignant | 2/442 (0.5%) | 2 | 1/440 (0.2%) | 1 |
| Nervous system disorders | ||||
| Autonomic nervous system imbalance | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Brain edema | 22/442 (5%) | 22 | 16/440 (3.6%) | 17 |
| Brain injury | 10/442 (2.3%) | 10 | 8/440 (1.8%) | 8 |
| Cerebral hemorrhage | 8/442 (1.8%) | 8 | 4/440 (0.9%) | 4 |
| Cerebral venous thrombosis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Cerebrospinal fluid rhinorrhea | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Chorea | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Convulsion | 6/442 (1.4%) | 6 | 8/440 (1.8%) | 9 |
| Headache | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Hemorrhage intracranial | 6/442 (1.4%) | 6 | 12/440 (2.7%) | 12 |
| Hepatic encephalopathy | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hydrocephalus | 12/442 (2.7%) | 12 | 8/440 (1.8%) | 8 |
| Intracranial hypotension | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Ischemic stroke | 5/442 (1.1%) | 5 | 13/440 (3%) | 13 |
| Neurological decompensation | 7/442 (1.6%) | 7 | 11/440 (2.5%) | 11 |
| Paresis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Status epilepticus | 3/442 (0.7%) | 3 | 0/440 (0%) | 0 |
| Subarachnoid hemorrhage | 1/442 (0.2%) | 1 | 3/440 (0.7%) | 3 |
| Vocal cord paresis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Psychiatric disorders | ||||
| Affective disorder | 3/442 (0.7%) | 3 | 3/440 (0.7%) | 4 |
| Alcohol withdrawal syndrome | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Impulsive behaviour | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Mental status changes | 8/442 (1.8%) | 9 | 7/440 (1.6%) | 7 |
| Personality change | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Suicide attempt | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Withdrawal syndrome | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Renal and urinary disorders | ||||
| Renal failure | 9/442 (2%) | 9 | 7/440 (1.6%) | 7 |
| Reproductive system and breast disorders | ||||
| Pelvic pain | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 4/442 (0.9%) | 5 | 8/440 (1.8%) | 8 |
| Aspiration | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Atelectasis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Bronchial secretion retention | 1/442 (0.2%) | 1 | 3/440 (0.7%) | 3 |
| Hemothorax | 2/442 (0.5%) | 2 | 3/440 (0.7%) | 3 |
| Hypoxia | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Pleural effusion | 2/442 (0.5%) | 2 | 3/440 (0.7%) | 3 |
| Pneumothorax | 12/442 (2.7%) | 13 | 6/440 (1.4%) | 6 |
| Pulmonary edema | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Pulmonary embolism | 11/442 (2.5%) | 11 | 11/440 (2.5%) | 11 |
| Respiratory distress | 4/442 (0.9%) | 4 | 11/440 (2.5%) | 11 |
| Respiratory failure | 22/442 (5%) | 22 | 16/440 (3.6%) | 16 |
| Stridor | 3/442 (0.7%) | 3 | 0/440 (0%) | 0 |
| Tracheal stenosis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Decubitus ulcer | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Subcutaneous emphysema | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Social circumstances | ||||
| Respite care | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Surgical and medical procedures | ||||
| Surgery | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Vascular disorders | ||||
| Aortic aneurysm rupture | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Artery dissection | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Circulatory collapse | 2/442 (0.5%) | 2 | 3/440 (0.7%) | 3 |
| Deep vein thrombosis | 33/442 (7.5%) | 36 | 27/440 (6.1%) | 27 |
| Hemorrhage | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Hypertension | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Phlebitis | 12/442 (2.7%) | 12 | 5/440 (1.1%) | 5 |
| Thrombosis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Progesterone | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 332/442 (75.1%) | 330/440 (75%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 8/442 (1.8%) | 9 | 11/440 (2.5%) | 12 |
| Coagulopathy | 3/442 (0.7%) | 3 | 1/440 (0.2%) | 1 |
| Leukocytosis | 12/442 (2.7%) | 13 | 6/440 (1.4%) | 6 |
| Thrombocytopenia | 4/442 (0.9%) | 5 | 7/440 (1.6%) | 7 |
| Thrombocytosis | 0/442 (0%) | 0 | 3/440 (0.7%) | 3 |
| Cardiac disorders | ||||
| Atrial fibrillation | 3/442 (0.7%) | 3 | 4/440 (0.9%) | 4 |
| Bradycardia | 5/442 (1.1%) | 6 | 10/440 (2.3%) | 11 |
| Extrasystoles | 2/442 (0.5%) | 2 | 1/440 (0.2%) | 1 |
| Myocardial infarction | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Supraventricular tachycardia | 4/442 (0.9%) | 4 | 2/440 (0.5%) | 2 |
| Tachycardia | 13/442 (2.9%) | 13 | 8/440 (1.8%) | 11 |
| Ventricular tachycardia | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Hypoacusis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Diabetes insipidus | 3/442 (0.7%) | 3 | 2/440 (0.5%) | 2 |
| Eye disorders | ||||
| Conjunctival oedema | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Diplopia | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Eye pain | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Mydriasis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Vision blurred | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| Constipation | 3/442 (0.7%) | 3 | 5/440 (1.1%) | 5 |
| Diarrhoea | 2/442 (0.5%) | 2 | 1/440 (0.2%) | 1 |
| Gastrointestinal hemorrhage | 3/442 (0.7%) | 3 | 2/440 (0.5%) | 2 |
| Nausea | 3/442 (0.7%) | 3 | 1/440 (0.2%) | 1 |
| Vomiting | 6/442 (1.4%) | 7 | 3/440 (0.7%) | 3 |
| General disorders | ||||
| Adverse drug reaction | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Catheter site hemorrhage | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Chest pain | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Chills | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Edema peripheral | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Infusion site edema | 12/442 (2.7%) | 14 | 4/440 (0.9%) | 5 |
| Infusion site erythema | 7/442 (1.6%) | 7 | 3/440 (0.7%) | 3 |
| Infusion site extravasation | 15/442 (3.4%) | 16 | 9/440 (2%) | 10 |
| Infusion site pain | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Local swelling | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Pyrexia | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Systemic inflammatory response syndrome | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Hepatitis alcoholic | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal abscess | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Bacteremia | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Bronchitis | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Candidiasis | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Cellulitis | 4/442 (0.9%) | 4 | 2/440 (0.5%) | 2 |
| Central nervous system infection | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Device related infection | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Fungal infection | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Mastoiditis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Pneumonia | 53/442 (12%) | 54 | 49/440 (11.1%) | 50 |
| Respiratory tract infection | 4/442 (0.9%) | 4 | 1/440 (0.2%) | 1 |
| Sepsis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Sinusitis | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Subcutaneous abscess | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Tracheobronchitis | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Urinary tract infection | 14/442 (3.2%) | 14 | 15/440 (3.4%) | 15 |
| Vaginal infection | 3/442 (0.7%) | 3 | 2/440 (0.5%) | 2 |
| Wound infection | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Injury, poisoning and procedural complications | ||||
| Endotracheal intubation complication | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Fall | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Heart injury | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Procedural complication | 3/442 (0.7%) | 3 | 1/440 (0.2%) | 1 |
| Subdural hemorrhage | 0/442 (0%) | 0 | 3/440 (0.7%) | 3 |
| Transfusion reaction | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Investigations | ||||
| Acid base balance abnormal | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Activated partial thromboplastin time prolonged | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Amylase increased | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Bacterial test positive | 6/442 (1.4%) | 6 | 2/440 (0.5%) | 2 |
| Blood albumin decreased | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 3 |
| Blood bicarbonate abnormal | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Blood bilirubin increased | 12/442 (2.7%) | 12 | 8/440 (1.8%) | 8 |
| Blood calcium abnormal | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Blood creatine phosphokinase increased | 3/442 (0.7%) | 3 | 2/440 (0.5%) | 2 |
| Blood fibrinogen increased | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Blood folate decreased | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Blood lactic acid increased | 7/442 (1.6%) | 8 | 1/440 (0.2%) | 1 |
| Blood magnesium abnormal | 0/442 (0%) | 0 | 3/440 (0.7%) | 3 |
| Blood osmolarity increased | 4/442 (0.9%) | 4 | 3/440 (0.7%) | 3 |
| Blood phosphorus abnormal | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Blood potassium abnormal | 2/442 (0.5%) | 2 | 4/440 (0.9%) | 4 |
| Blood sodium abnormal | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Blood urea increased | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Cardiac enzymes increased | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Drug level below therapeutic | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Electrocardiogram ST segment elevation | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Full blood count abnormal | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hepatic enzyme increased | 8/442 (1.8%) | 8 | 8/440 (1.8%) | 8 |
| International normalised ratio increased | 4/442 (0.9%) | 4 | 1/440 (0.2%) | 1 |
| Myoglobin blood increased | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Prealbumin decreased | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| White blood cell count abnormal | 2/442 (0.5%) | 2 | 4/440 (0.9%) | 4 |
| Metabolism and nutrition disorders | ||||
| Acidosis | 7/442 (1.6%) | 7 | 11/440 (2.5%) | 11 |
| Alkalosis | 9/442 (2%) | 9 | 8/440 (1.8%) | 8 |
| Fluid overload | 4/442 (0.9%) | 4 | 4/440 (0.9%) | 4 |
| Hyperchloremia | 7/442 (1.6%) | 9 | 9/440 (2%) | 9 |
| Hyperglycemia | 6/442 (1.4%) | 6 | 4/440 (0.9%) | 4 |
| Hyperkalemia | 8/442 (1.8%) | 8 | 3/440 (0.7%) | 3 |
| Hyperlipidemia | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Hypermagnesemia | 5/442 (1.1%) | 6 | 5/440 (1.1%) | 5 |
| Hypernatremia | 21/442 (4.8%) | 21 | 29/440 (6.6%) | 29 |
| Hyperphosphatemia | 6/442 (1.4%) | 6 | 2/440 (0.5%) | 2 |
| Hypocalcemia | 78/442 (17.6%) | 83 | 101/440 (23%) | 110 |
| Hypochloremia | 2/442 (0.5%) | 2 | 1/440 (0.2%) | 1 |
| Hypoglycemia | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Hypokalemia | 72/442 (16.3%) | 83 | 111/440 (25.2%) | 129 |
| Hypomagnesemia | 90/442 (20.4%) | 101 | 94/440 (21.4%) | 100 |
| Hyponatremia | 29/442 (6.6%) | 30 | 20/440 (4.5%) | 21 |
| Hypophosphatemia | 134/442 (30.3%) | 145 | 134/440 (30.5%) | 146 |
| Hypovolemia | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Propofol infusion syndrome | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Compartment syndrome | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Muscular weakness | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Musculoskeletal pain | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Rhabdomyolysis | 3/442 (0.7%) | 3 | 3/440 (0.7%) | 3 |
| Soft tissue necrosis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Nervous system disorders | ||||
| Autonomic nervous system imbalance | 2/442 (0.5%) | 2 | 4/440 (0.9%) | 4 |
| Brain edema | 0/442 (0%) | 0 | 3/440 (0.7%) | 3 |
| Cerebral hemorrhage | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Cerebral venous thrombosis | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Cerebrospinal fluid rhinorrhea | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Convulsion | 5/442 (1.1%) | 5 | 9/440 (2%) | 9 |
| Dizziness | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Headache | 3/442 (0.7%) | 3 | 4/440 (0.9%) | 4 |
| Hemorrhage intracranial | 3/442 (0.7%) | 3 | 4/440 (0.9%) | 4 |
| Ischemic stroke | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Neurological decompensation | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Paresis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Tremor | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| VIth nerve disorder | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Psychiatric disorders | ||||
| Affective disorder | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Alcohol withdrawal syndrome | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Impulsive behaviour | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Mental status changes | 10/442 (2.3%) | 11 | 10/440 (2.3%) | 10 |
| Withdrawal syndrome | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Renal and urinary disorders | ||||
| Hematuria | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Nephrolithiasis | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Renal failure | 3/442 (0.7%) | 3 | 7/440 (1.6%) | 7 |
| Urinary retention | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Aspiration | 2/442 (0.5%) | 2 | 0/440 (0%) | 0 |
| Atelectasis | 8/442 (1.8%) | 8 | 4/440 (0.9%) | 4 |
| Epistaxis | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Hemothorax | 1/442 (0.2%) | 1 | 1/440 (0.2%) | 1 |
| Hiccups | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hypocapnia | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Hypoxia | 2/442 (0.5%) | 2 | 2/440 (0.5%) | 2 |
| Lung infiltration | 2/442 (0.5%) | 2 | 4/440 (0.9%) | 4 |
| Pleural effusion | 4/442 (0.9%) | 4 | 5/440 (1.1%) | 5 |
| Pneumomediastinum | 1/442 (0.2%) | 1 | 2/440 (0.5%) | 2 |
| Pneumothorax | 9/442 (2%) | 10 | 22/440 (5%) | 24 |
| Pulmonary edema | 4/442 (0.9%) | 4 | 6/440 (1.4%) | 6 |
| Pulmonary embolism | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Respiratory distress | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Respiratory failure | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Tachypnoea | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Decubitus ulcer | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Erythema | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Pruritus | 3/442 (0.7%) | 3 | 0/440 (0%) | 0 |
| Rash | 6/442 (1.4%) | 6 | 6/440 (1.4%) | 6 |
| Subcutaneous emphysema | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Vascular disorders | ||||
| Artery dissection | 0/442 (0%) | 0 | 2/440 (0.5%) | 2 |
| Deep vein thrombosis | 20/442 (4.5%) | 22 | 13/440 (3%) | 13 |
| Hemorrhage | 1/442 (0.2%) | 1 | 0/440 (0%) | 0 |
| Hypertension | 2/442 (0.5%) | 3 | 2/440 (0.5%) | 2 |
| Hypotension | 0/442 (0%) | 0 | 1/440 (0.2%) | 2 |
| Peripheral ischemia | 0/442 (0%) | 0 | 1/440 (0.2%) | 1 |
| Phlebitis | 74/442 (16.7%) | 89 | 24/440 (5.5%) | 27 |
| Thrombosis | 2/442 (0.5%) | 3 | 2/440 (0.5%) | 2 |
Limitations/Caveats
The trial was stopped early for futility with respect to the primary outcome.
More Information
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 |
| david.wright@emory.edu |
Responsible Party:
David Wright,
Principal Investigator,
Emory University
ClinicalTrials.gov Identifier:
NCT00822900
Other Study ID Numbers:
- IRB00014409
- 1RO1 NS062778-01
First Posted:
Jan 15, 2009
Last Update Posted:
Jan 20, 2016
Last Verified:
Dec 1, 2015