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Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-OH [Out of Hospital] Trial (THAPCA-OH)

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ClinicalTrials.gov Identifier: NCT00878644
Recruitment Status : Completed
First Posted : April 9, 2009
Results First Posted : September 29, 2017
Last Update Posted : September 29, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Frank W. Moler, M.D, M.S, University of Michigan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Cardiac Arrest
Interventions Procedure: Therapeutic Hypothermia
Other: Therapeutic Normothermia
Enrollment 295
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia
Hide Arm/Group Description

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Period Title: Overall Study
Started 155 140
Completed 151 136
Not Completed 4 4
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia Total
Hide Arm/Group Description

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Total of all reporting groups
Overall Number of Baseline Participants 155 140 295
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 155 participants 140 participants 295 participants
2.1
(0.6 to 10.1)
1.6
(0.4 to 7.0)
2.0
(0.5 to 8.7)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age Category Number Analyzed 155 participants 140 participants 295 participants
< 2 yr
76
  49.0%
73
  52.1%
149
  50.5%
2 - <12 yr
48
  31.0%
45
  32.1%
93
  31.5%
12 - 17 yr
31
  20.0%
22
  15.7%
53
  18.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 140 participants 295 participants
Female
53
  34.2%
46
  32.9%
99
  33.6%
Male
102
  65.8%
94
  67.1%
196
  66.4%
1.Primary Outcome
Title Survival With Good Neurobehavioral Outcome
Hide Description Survival at one-year anniversary of cardiac arrest, with a standardized VABS-II score of 70 or greater per evaluation performed at any time from 30 days prior to until 183 days after the one-year anniversary of cardiac arrest.
Time Frame Survival was assessed at one-year anniversary of cardiac arrest; among survivors at this one-year anniversary, the VABS-II valid assessment window ranged from 30 days prior to until 183 days after the one-year anniversary date.
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with baseline VABS-II >= 70, OR unavailable baseline VABS-II but Pediatric Overall Performance Category (POPC) score and Pediatric Cerebral Overall Performance Category (PCPC) both reflecting none or mild disability (1 or 2), are eligible for the primary analysis. Population is analysis-eligible patients with available primary outcome.
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia
Hide Arm/Group Description:

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Overall Number of Participants Analyzed 138 122
Measure Type: Count of Participants
Unit of Measure: Participants
Alive with VABS-II >=70 at 1 year
27
  19.6%
15
  12.3%
Died or Alive with VABS-II <70 at 1 year
111
  80.4%
107
  87.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Therapeutic Hypothermia, Therapeutic Normothermia
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test was used adjusting for age category at time of randomization (<2 years, 2 to <12 years, or >=12 years)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
-1.5 to 16.1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Survival
Hide Description Survival at one year after cardiac arrest
Time Frame Measured at one-year anniversary of cardiac arrest.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients with available vital status (alive or deceased) at one year after cardiac arrest.
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia
Hide Arm/Group Description:

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Overall Number of Participants Analyzed 151 136
Measure Type: Count of Participants
Unit of Measure: Participants
Alive at 1 year
57
  37.7%
39
  28.7%
Died at 1 year
94
  62.3%
97
  71.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Therapeutic Hypothermia, Therapeutic Normothermia
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test was used adjusting for age category at time of randomization (<2 years, 2 to <12 years, or >=12 years)
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 9.1
Confidence Interval (2-Sided) 95%
-1.8 to 19.9
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest
Hide Description Change in VABS-II score from baseline to one year, with death at 1 year treated as worst possible outcome, and lowest possible VABS-II score at one year (regardless of baseline VABS-II score) treated as the second worst possible outcome.
Time Frame Survival was assessed at one-year anniversary of cardiac arrest; among survivors at this one-year anniversary, the VABS-II valid assessment window ranged from 30 days prior to until 183 days after the one-year anniversary date.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects with available data for this outcome (this implies a child must be either dead at 1 year, have the lowest possible value for the VABS-II score at 1 year, or if neither of these two criteria applies, must have both baseline VABS-II and 1-year VABS-II scores available to allow calculation of change in VABS-II score)
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia
Hide Arm/Group Description:

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Overall Number of Participants Analyzed 151 134
Measure Type: Count of Participants
Unit of Measure: Participants
Dead at 1 year
94
  62.3%
97
  72.4%
Lowest possible VABS-II at 1 year
6
   4.0%
1
   0.7%
1-year decrease in VABS-II >30 points
19
  12.6%
15
  11.2%
1-year decrease in VABS-II 16-30 points
11
   7.3%
4
   3.0%
1-year decrease in VABS-II <=15 points or improved
21
  13.9%
17
  12.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Therapeutic Hypothermia, Therapeutic Normothermia
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Stratified Mann-Whitney Test
Comments Test stratified by age category (<2 years, 2 to <12 years, or >=12 years), for continuous (NOT categorized as reported above) 1-year change in VABS-II
Other Statistical Analysis As the (nonparametric) comparison treated 1-year deaths as worst possible outcomes and worst possible 1-year VABS-II as next worst possible outcomes, using change in VABS-II for other participants alive at 1 year, no relevant estimation of effect size is possible for this secondary outcome.
4.Secondary Outcome
Title Neuropsychological Scores (for Participants That Survive)
Hide Description Functioning, as assessed by the Mullen Early Learning Composite (for children age < 5 years 9 months) or by the 2-subset version of the Wechsler Abbreviated Scale of Intelligence (WASI). As these two function measures are scaled in the same fashion, the two age groups are combined.
Time Frame Measured at Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized children alive at one year with neuropsychological score available.
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia
Hide Arm/Group Description:

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Overall Number of Participants Analyzed 52 35
Measure Type: Count of Participants
Unit of Measure: Participants
Lowest possible score
27
  51.9%
17
  48.6%
<70 (well below average)
7
  13.5%
8
  22.9%
70 - 84 (below average)
5
   9.6%
6
  17.1%
85 - 115 (average)
8
  15.4%
2
   5.7%
>115 (above average)
5
   9.6%
2
   5.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Therapeutic Hypothermia, Therapeutic Normothermia
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Test used the continuous (NOT categorized as reported above) neuropsychological scores, with "Lowest Possible Score" treated as lowest possible value.
Time Frame For all-cause mortality, results reflect vital status at 12 months. Serious adverse events and other (not serious) adverse events were collected for 14 days after treatment was initiated.
Adverse Event Reporting Description For adverse events, denominators reflect Safety Population of those patients receiving each treatment. Therefore, denominators are 153 patients receiving Therapeutic Hypothermia and 139 patients receiving Therapeutic Normothermia. For all-cause mortality, denominators additionally include only those with known 12-month vital status.
 
Arm/Group Title Therapeutic Hypothermia Therapeutic Normothermia
Hide Arm/Group Description

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Therapeutic Hypothermia: Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Therapeutic Normothermia: Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

All-Cause Mortality
Therapeutic Hypothermia Therapeutic Normothermia
Affected / at Risk (%) Affected / at Risk (%)
Total   92/149 (61.74%)      96/135 (71.11%)    
Hide Serious Adverse Events
Therapeutic Hypothermia Therapeutic Normothermia
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   98/153 (64.05%)      102/139 (73.38%)    
Blood and lymphatic system disorders     
Disseminated intravascular coagulation  0/153 (0.00%)  0 1/139 (0.72%)  1
Cardiac disorders     
Bigeminy  1/153 (0.65%)  1 0/139 (0.00%)  0
Bradycardia  3/153 (1.96%)  3 3/139 (2.16%)  3
Cardiac arrest  5/153 (3.27%)  6 9/139 (6.47%)  10
Cardiac failure  0/153 (0.00%)  0 3/139 (2.16%)  3
Cardiac failure aggravated  0/153 (0.00%)  0 2/139 (1.44%)  2
Myocarditis  1/153 (0.65%)  1 0/139 (0.00%)  0
Pulseless electrical activity  1/153 (0.65%)  1 0/139 (0.00%)  0
Torsades de pointes  2/153 (1.31%)  2 0/139 (0.00%)  0
Ventricular tachycardia  0/153 (0.00%)  0 1/139 (0.72%)  1
Endocrine disorders     
Diabetes insipidus  0/153 (0.00%)  0 2/139 (1.44%)  2
Eye disorders     
Anisocoria  1/153 (0.65%)  1 0/139 (0.00%)  0
Gastrointestinal disorders     
Pneumatosis intestinalis  0/153 (0.00%)  0 1/139 (0.72%)  1
General disorders     
Multi organ failure  0/153 (0.00%)  0 1/139 (0.72%)  1
Multi-organ disorder  0/153 (0.00%)  0 1/139 (0.72%)  1
Multi-organ failure  1/153 (0.65%)  1 1/139 (0.72%)  1
Multiorgan failure  1/153 (0.65%)  1 0/139 (0.00%)  0
Multiple organ failure  2/153 (1.31%)  2 2/139 (1.44%)  2
Shivering  1/153 (0.65%)  1 0/139 (0.00%)  0
Sudden infant death syndrome  1/153 (0.65%)  1 0/139 (0.00%)  0
Hepatobiliary disorders     
Liver failure  1/153 (0.65%)  1 0/139 (0.00%)  0
Infections and infestations     
Candida albicans infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Infection pseudomonas aeruginosa  0/153 (0.00%)  0 1/139 (0.72%)  2
Respiratory infection  4/153 (2.61%)  4 5/139 (3.60%)  6
Respiratory syncytial virus infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Sepsis  0/153 (0.00%)  0 1/139 (0.72%)  1
Septic shock  1/153 (0.65%)  1 1/139 (0.72%)  1
Streptococcal infection  1/153 (0.65%)  1 0/139 (0.00%)  0
Tracheitis  0/153 (0.00%)  0 1/139 (0.72%)  1
Urinary infection  2/153 (1.31%)  2 0/139 (0.00%)  0
Injury, poisoning and procedural complications     
Brain herniation  5/153 (3.27%)  5 5/139 (3.60%)  5
Brain stem herniation  1/153 (0.65%)  1 0/139 (0.00%)  0
Carbon monoxide poisoning  0/153 (0.00%)  0 1/139 (0.72%)  1
Investigations     
Cardiac output decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
HIE  2/153 (1.31%)  2 1/139 (0.72%)  1
QT interval prolonged  1/153 (0.65%)  1 0/139 (0.00%)  0
Sputum culture positive  0/153 (0.00%)  0 1/139 (0.72%)  1
Urine culture positive  0/153 (0.00%)  0 2/139 (1.44%)  2
Metabolism and nutrition disorders     
Hypocalcemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Hypoglycemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Hypokalemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Metabolic acidosis  2/153 (1.31%)  2 0/139 (0.00%)  0
Nervous system disorders     
Anoxic brain damage  14/153 (9.15%)  14 14/139 (10.07%)  14
Anoxic encephalopathy  1/153 (0.65%)  1 2/139 (1.44%)  2
Basal ganglia infarction  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral edema  13/153 (8.50%)  13 15/139 (10.79%)  15
Cerebral infarct  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral infarction  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral ischaemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral ischemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Hypoxic brain damage  10/153 (6.54%)  10 4/139 (2.88%)  4
Hypoxic encephalopathy  18/153 (11.76%)  18 21/139 (15.11%)  21
Intracranial hemorrhage  0/153 (0.00%)  0 1/139 (0.72%)  1
Ischemia cerebral  0/153 (0.00%)  0 2/139 (1.44%)  2
Loss of gag reflex  0/153 (0.00%)  0 1/139 (0.72%)  1
Neurological status deterioration  1/153 (0.65%)  1 1/139 (0.72%)  1
Renal and urinary disorders     
Acute renal failure  0/153 (0.00%)  0 1/139 (0.72%)  1
Renal failure  1/153 (0.65%)  1 0/139 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ARDS  0/153 (0.00%)  0 1/139 (0.72%)  1
Acute respiratory distress syndrome  1/153 (0.65%)  1 0/139 (0.00%)  0
Alkalosis respiratory  1/153 (0.65%)  1 0/139 (0.00%)  0
Asthma  0/153 (0.00%)  0 1/139 (0.72%)  1
Pneumothorax  1/153 (0.65%)  2 1/139 (0.72%)  1
Pulmonary edema aggravated  1/153 (0.65%)  1 0/139 (0.00%)  0
Pulmonary hemorrhage  1/153 (0.65%)  1 1/139 (0.72%)  1
Respiratory acidosis  1/153 (0.65%)  1 0/139 (0.00%)  0
Respiratory distress  0/153 (0.00%)  0 1/139 (0.72%)  1
Respiratory failure  2/153 (1.31%)  2 2/139 (1.44%)  2
Respiratory failure aggravated  0/153 (0.00%)  0 1/139 (0.72%)  1
Upper airway obstruction  1/153 (0.65%)  2 0/139 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin ulcer  0/153 (0.00%)  0 1/139 (0.72%)  1
Vascular disorders     
Cardiovascular collapse  1/153 (0.65%)  1 0/139 (0.00%)  0
Circulatory failure  1/153 (0.65%)  1 0/139 (0.00%)  0
DVT  1/153 (0.65%)  1 1/139 (0.72%)  1
Hemodynamic instability  1/153 (0.65%)  1 1/139 (0.72%)  1
Hypotension  3/153 (1.96%)  3 4/139 (2.88%)  4
Ischemia  2/153 (1.31%)  2 4/139 (2.88%)  4
1
Term from vocabulary, MedDRA (13.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Therapeutic Hypothermia Therapeutic Normothermia
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   145/153 (94.77%)      124/139 (89.21%)    
Blood and lymphatic system disorders     
Anemia  30/153 (19.61%)  32 18/139 (12.95%)  19
Clotting  0/153 (0.00%)  0 1/139 (0.72%)  1
Coagulation disorder  1/153 (0.65%)  1 0/139 (0.00%)  0
Coagulopathy  16/153 (10.46%)  16 9/139 (6.47%)  9
DIC  3/153 (1.96%)  3 2/139 (1.44%)  2
Disseminated intravascular coagulation  1/153 (0.65%)  1 1/139 (0.72%)  1
Hypercoagulation  1/153 (0.65%)  1 0/139 (0.00%)  0
Leukocytosis  5/153 (3.27%)  5 5/139 (3.60%)  5
Leukopenia  9/153 (5.88%)  9 2/139 (1.44%)  2
Lymphopenia  5/153 (3.27%)  5 0/139 (0.00%)  0
Methemoglobinemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Neutropenia  4/153 (2.61%)  4 1/139 (0.72%)  1
Splenic infarction  1/153 (0.65%)  1 0/139 (0.00%)  0
Thrombocytopenia  16/153 (10.46%)  16 2/139 (1.44%)  2
Cardiac disorders     
2nd degree heart block  1/153 (0.65%)  1 0/139 (0.00%)  0
Arrhythmia  2/153 (1.31%)  2 0/139 (0.00%)  0
Atrial arrhythmia  1/153 (0.65%)  1 0/139 (0.00%)  0
Atrial flutter  1/153 (0.65%)  2 0/139 (0.00%)  0
Atrial tachycardia  0/153 (0.00%)  0 1/139 (0.72%)  1
Bigeminy  1/153 (0.65%)  1 0/139 (0.00%)  0
Bradycardia  12/153 (7.84%)  12 5/139 (3.60%)  5
Bundle branch block  0/153 (0.00%)  0 1/139 (0.72%)  1
Cardiac failure  1/153 (0.65%)  1 1/139 (0.72%)  1
Cardiac ischemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Cardiomegaly  2/153 (1.31%)  2 1/139 (0.72%)  1
Fibrosis myocardial  0/153 (0.00%)  0 1/139 (0.72%)  1
Junctional arrhythmia  1/153 (0.65%)  1 0/139 (0.00%)  0
Junctional rhythm  0/153 (0.00%)  0 1/139 (0.72%)  1
Left ventricular dysfunction  2/153 (1.31%)  2 1/139 (0.72%)  1
Left ventricular systolic dysfunction  0/153 (0.00%)  0 1/139 (0.72%)  1
Mitral regurgitation  1/153 (0.65%)  1 0/139 (0.00%)  0
Myocardial depression  2/153 (1.31%)  2 1/139 (0.72%)  1
PVC's  3/153 (1.96%)  3 1/139 (0.72%)  1
Pericardial effusion  1/153 (0.65%)  1 0/139 (0.00%)  0
Pneumopericardium  2/153 (1.31%)  2 0/139 (0.00%)  0
Premature ventricular contractions  1/153 (0.65%)  1 1/139 (0.72%)  1
Right ventricular dysfunction  1/153 (0.65%)  1 0/139 (0.00%)  0
SVT  2/153 (1.31%)  2 0/139 (0.00%)  0
Sinus tachycardia  0/153 (0.00%)  0 1/139 (0.72%)  1
Stenosis pulmonic valve  1/153 (0.65%)  1 0/139 (0.00%)  0
Tachycardia  2/153 (1.31%)  2 7/139 (5.04%)  8
Ventricular bigeminy  1/153 (0.65%)  1 0/139 (0.00%)  0
Ventricular fibrillation  1/153 (0.65%)  1 0/139 (0.00%)  0
Ventricular tachycardia  1/153 (0.65%)  1 3/139 (2.16%)  3
Congenital, familial and genetic disorders     
Hydrocele male  1/153 (0.65%)  1 0/139 (0.00%)  0
Ear and labyrinth disorders     
Ear discharge  1/153 (0.65%)  1 0/139 (0.00%)  0
Hearing loss  1/153 (0.65%)  1 0/139 (0.00%)  0
Endocrine disorders     
Adrenal insufficiency  0/153 (0.00%)  0 2/139 (1.44%)  2
Diabetes insipidus  16/153 (10.46%)  16 20/139 (14.39%)  20
Eye disorders     
Anisocoria  1/153 (0.65%)  1 1/139 (0.72%)  1
Dilatation pupillary  0/153 (0.00%)  0 1/139 (0.72%)  1
Dilated pupils  0/153 (0.00%)  0 1/139 (0.72%)  1
Eye movement disorder  1/153 (0.65%)  1 0/139 (0.00%)  0
Fixed dilated pupils  0/153 (0.00%)  0 1/139 (0.72%)  1
Gaze palsy  0/153 (0.00%)  0 1/139 (0.72%)  1
Pupil fixed  1/153 (0.65%)  1 0/139 (0.00%)  0
Pupillary reaction slow  0/153 (0.00%)  0 1/139 (0.72%)  1
Retinal hemorrhage  1/153 (0.65%)  1 3/139 (2.16%)  3
Retinopathy hemorrhagic  0/153 (0.00%)  0 1/139 (0.72%)  1
Gastrointestinal disorders     
Abdominal distension  3/153 (1.96%)  3 0/139 (0.00%)  0
Ascites  1/153 (0.65%)  1 2/139 (1.44%)  2
Bleeding mouth  1/153 (0.65%)  1 0/139 (0.00%)  0
Bloody stool  1/153 (0.65%)  1 0/139 (0.00%)  0
Bowel ischemia  2/153 (1.31%)  2 1/139 (0.72%)  1
Chapped lips  1/153 (0.65%)  1 0/139 (0.00%)  0
Constipation  3/153 (1.96%)  3 2/139 (1.44%)  2
Diarrhea  3/153 (1.96%)  3 3/139 (2.16%)  3
Distended abdomen  1/153 (0.65%)  1 1/139 (0.72%)  1
Dysphagia  2/153 (1.31%)  2 0/139 (0.00%)  0
Emesis  4/153 (2.61%)  4 3/139 (2.16%)  3
Esophageal tear  1/153 (0.65%)  1 0/139 (0.00%)  0
Fecal impaction  1/153 (0.65%)  1 0/139 (0.00%)  0
GI bleed  1/153 (0.65%)  1 1/139 (0.72%)  1
Gas  1/153 (0.65%)  1 0/139 (0.00%)  0
Gastritis  1/153 (0.65%)  1 0/139 (0.00%)  0
Gastroesophageal reflux  0/153 (0.00%)  0 1/139 (0.72%)  1
Gastrointestinal bleeding  1/153 (0.65%)  1 1/139 (0.72%)  1
Gastrointestinal mucosal sloughing  2/153 (1.31%)  2 2/139 (1.44%)  2
Gum erosion  0/153 (0.00%)  0 1/139 (0.72%)  1
Intestinal edema  1/153 (0.65%)  1 0/139 (0.00%)  0
Localised intraabdominal fluid collection  1/153 (0.65%)  1 0/139 (0.00%)  0
Loose stools  1/153 (0.65%)  1 0/139 (0.00%)  0
Nausea  0/153 (0.00%)  0 1/139 (0.72%)  1
Oral discharge  1/153 (0.65%)  1 0/139 (0.00%)  0
Pancreatitis  9/153 (5.88%)  9 7/139 (5.04%)  7
Pancreatitis aggravated  0/153 (0.00%)  0 1/139 (0.72%)  1
Pneumatosis intestinalis  0/153 (0.00%)  0 1/139 (0.72%)  1
Pneumoperitoneum  1/153 (0.65%)  1 1/139 (0.72%)  1
Saliva secretion excessive  0/153 (0.00%)  0 1/139 (0.72%)  1
Stools watery  0/153 (0.00%)  0 1/139 (0.72%)  1
Swallowing difficult  1/153 (0.65%)  1 0/139 (0.00%)  0
Swallowing disorder  0/153 (0.00%)  0 1/139 (0.72%)  1
UGI bleed  1/153 (0.65%)  1 0/139 (0.00%)  0
Vomited  1/153 (0.65%)  1 0/139 (0.00%)  0
Vomiting  5/153 (3.27%)  5 2/139 (1.44%)  2
General disorders     
Anasarca  1/153 (0.65%)  1 3/139 (2.16%)  3
Catheter related complication  1/153 (0.65%)  1 0/139 (0.00%)  0
Catheter site bleeding  0/153 (0.00%)  0 2/139 (1.44%)  2
Drug withdrawal syndrome  3/153 (1.96%)  3 0/139 (0.00%)  0
Edema  7/153 (4.58%)  7 4/139 (2.88%)  4
Edema abdomen  1/153 (0.65%)  1 0/139 (0.00%)  0
Edema extremity upper  1/153 (0.65%)  1 0/139 (0.00%)  0
Edema hands  1/153 (0.65%)  1 0/139 (0.00%)  0
Edema of extremities  0/153 (0.00%)  0 1/139 (0.72%)  1
Edema of lower extremities  1/153 (0.65%)  1 2/139 (1.44%)  2
Edema thigh  1/153 (0.65%)  1 0/139 (0.00%)  0
Edema trunk  1/153 (0.65%)  1 0/139 (0.00%)  0
Extravasation  0/153 (0.00%)  0 1/139 (0.72%)  1
Face oedema  1/153 (0.65%)  1 2/139 (1.44%)  2
Fever  16/153 (10.46%)  18 10/139 (7.19%)  10
Generalized edema  2/153 (1.31%)  2 1/139 (0.72%)  1
Hand swelling  1/153 (0.65%)  1 0/139 (0.00%)  0
High temperature  1/153 (0.65%)  1 0/139 (0.00%)  0
Hyperpyrexia  1/153 (0.65%)  2 0/139 (0.00%)  0
Hyperthermia  2/153 (1.31%)  2 2/139 (1.44%)  3
Hypothermia  1/153 (0.65%)  1 4/139 (2.88%)  4
Infiltration intravenous injection  1/153 (0.65%)  1 0/139 (0.00%)  0
Infusion site erythema  0/153 (0.00%)  0 1/139 (0.72%)  1
Infusion site extravasation  2/153 (1.31%)  2 0/139 (0.00%)  0
Infusion site infiltration  1/153 (0.65%)  1 0/139 (0.00%)  0
Intermittent fever  1/153 (0.65%)  1 0/139 (0.00%)  0
Leg edema  1/153 (0.65%)  1 0/139 (0.00%)  0
Multi organ failure  1/153 (0.65%)  1 0/139 (0.00%)  0
Multi-organ disorder  0/153 (0.00%)  0 1/139 (0.72%)  1
Neck edema  1/153 (0.65%)  1 0/139 (0.00%)  0
Pain aggravated  1/153 (0.65%)  1 0/139 (0.00%)  0
Peripheral edema  1/153 (0.65%)  1 0/139 (0.00%)  0
Pyrexia  0/153 (0.00%)  0 1/139 (0.72%)  1
Shivering  8/153 (5.23%)  9 5/139 (3.60%)  5
Swelling of legs  3/153 (1.96%)  3 1/139 (0.72%)  1
Swelling of limb  0/153 (0.00%)  0 1/139 (0.72%)  1
Hepatobiliary disorders     
Acute liver injury  0/153 (0.00%)  0 1/139 (0.72%)  1
Gallbladder edema  0/153 (0.00%)  0 1/139 (0.72%)  1
Hepatitis  1/153 (0.65%)  1 0/139 (0.00%)  0
Hepatomegaly  0/153 (0.00%)  0 1/139 (0.72%)  1
Hyperbilirubinemia  1/153 (0.65%)  1 1/139 (0.72%)  1
Liver failure  0/153 (0.00%)  0 1/139 (0.72%)  1
Infections and infestations     
Adenovirus infection  1/153 (0.65%)  1 0/139 (0.00%)  0
Bacteremia  2/153 (1.31%)  2 0/139 (0.00%)  0
Bacterial infection due to staphylococcus aureus  0/153 (0.00%)  0 1/139 (0.72%)  1
Bacterial tracheitis  1/153 (0.65%)  1 3/139 (2.16%)  3
Bilateral pneumonia  1/153 (0.65%)  1 1/139 (0.72%)  1
Candida albicans infection  1/153 (0.65%)  1 0/139 (0.00%)  0
Catheter site infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Central line infection  1/153 (0.65%)  1 1/139 (0.72%)  1
Clostridium difficile infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Clostridium difficile sepsis  1/153 (0.65%)  1 0/139 (0.00%)  0
Enterobacter cloacae infection  1/153 (0.65%)  1 0/139 (0.00%)  0
Enterococcal sepsis  1/153 (0.65%)  1 0/139 (0.00%)  0
Enterococcal urinary tract infection  3/153 (1.96%)  3 0/139 (0.00%)  0
Enterovirus infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Escherichia coli infection  1/153 (0.65%)  1 1/139 (0.72%)  1
Escherichia sepsis  1/153 (0.65%)  1 0/139 (0.00%)  0
Escherichia urinary tract infection  4/153 (2.61%)  4 3/139 (2.16%)  3
Gram-positive cocci infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Haemophilus influenzae infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Herpes sepsis  1/153 (0.65%)  1 0/139 (0.00%)  0
Infection MRSA  1/153 (0.65%)  1 0/139 (0.00%)  0
Klebsiella pneumonia  0/153 (0.00%)  0 1/139 (0.72%)  1
Klebsiella pneumoniae infection  2/153 (1.31%)  2 1/139 (0.72%)  1
Klebsiella sepsis  1/153 (0.65%)  1 0/139 (0.00%)  0
Lung infection  0/153 (0.00%)  0 1/139 (0.72%)  1
MRSA  1/153 (0.65%)  1 0/139 (0.00%)  0
Moraxella catarrhalis pneumonia  1/153 (0.65%)  1 0/139 (0.00%)  0
Pansinusitis  1/153 (0.65%)  1 0/139 (0.00%)  0
Pneumonia  6/153 (3.92%)  7 3/139 (2.16%)  3
Pseudomonas aeruginosa infection NOS  0/153 (0.00%)  0 1/139 (0.72%)  1
Respiratory infection  15/153 (9.80%)  19 5/139 (3.60%)  5
Respiratory syncytial virus infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Respiratory tract infection bacterial  0/153 (0.00%)  0 2/139 (1.44%)  2
Rhinovirus infection  3/153 (1.96%)  3 5/139 (3.60%)  5
Sepsis  2/153 (1.31%)  2 0/139 (0.00%)  0
Septic shock  0/153 (0.00%)  0 1/139 (0.72%)  1
Septicemia  0/153 (0.00%)  0 1/139 (0.72%)  1
Septicemia due to Escherichia coli (E. coli)  0/153 (0.00%)  0 1/139 (0.72%)  1
Septicemia pseudomonal  1/153 (0.65%)  1 0/139 (0.00%)  0
Serous otitis media (glue ear)  0/153 (0.00%)  0 1/139 (0.72%)  1
Sinusitis  1/153 (0.65%)  1 3/139 (2.16%)  3
Soft tissue infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Staphylococcal infection  1/153 (0.65%)  1 1/139 (0.72%)  1
Staphylococcal pneumonia  1/153 (0.65%)  1 1/139 (0.72%)  1
Staphylococcal sepsis  1/153 (0.65%)  1 0/139 (0.00%)  0
Staphylococcus aureus bacteremia  1/153 (0.65%)  1 0/139 (0.00%)  0
Staphylococcus aureus cellulitis  1/153 (0.65%)  1 0/139 (0.00%)  0
Staphylococcus aureus pneumonia  1/153 (0.65%)  1 1/139 (0.72%)  1
Stenotrophomonas maltophilia infection  1/153 (0.65%)  1 0/139 (0.00%)  0
Streptococcal septicemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Streptococcus pneumoniae pneumonia  1/153 (0.65%)  1 0/139 (0.00%)  0
Streptococcus viridans group infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Thrush  2/153 (1.31%)  2 0/139 (0.00%)  0
Tracheitis  3/153 (1.96%)  3 1/139 (0.72%)  1
UTI  1/153 (0.65%)  1 1/139 (0.72%)  1
Urinary tract infection  2/153 (1.31%)  3 2/139 (1.44%)  2
Urinary tract infection bacterial  2/153 (1.31%)  2 1/139 (0.72%)  1
Urine candida  0/153 (0.00%)  0 1/139 (0.72%)  1
Ventilator associated pneumonia  2/153 (1.31%)  2 1/139 (0.72%)  1
Yeast infection  0/153 (0.00%)  0 1/139 (0.72%)  1
Yeast infection of the mouth  1/153 (0.65%)  1 0/139 (0.00%)  0
Injury, poisoning and procedural complications     
Abrasions  3/153 (1.96%)  3 0/139 (0.00%)  0
Barotrauma  1/153 (0.65%)  1 0/139 (0.00%)  0
Bloody airway discharge  1/153 (0.65%)  2 1/139 (0.72%)  1
Brain herniation  1/153 (0.65%)  1 1/139 (0.72%)  1
Bruise  1/153 (0.65%)  1 0/139 (0.00%)  0
Bruise of head  1/153 (0.65%)  1 0/139 (0.00%)  0
Bruising  1/153 (0.65%)  1 0/139 (0.00%)  0
Bruising of hand  1/153 (0.65%)  1 0/139 (0.00%)  0
Collapse of lung  2/153 (1.31%)  2 1/139 (0.72%)  1
Corneal abrasion  1/153 (0.65%)  1 0/139 (0.00%)  0
Femur fracture  1/153 (0.65%)  1 1/139 (0.72%)  1
Fracture of upper end or unspecified part of radius and ulna, closed  0/153 (0.00%)  0 1/139 (0.72%)  1
Fractured cervical spine  0/153 (0.00%)  0 1/139 (0.72%)  1
Humerus fracture  0/153 (0.00%)  0 1/139 (0.72%)  1
Iatrogenic pneumothorax  0/153 (0.00%)  0 1/139 (0.72%)  1
Ligament injury  0/153 (0.00%)  0 1/139 (0.72%)  1
Lip injury  1/153 (0.65%)  1 0/139 (0.00%)  0
Lung injury  1/153 (0.65%)  1 1/139 (0.72%)  1
Renal injury  0/153 (0.00%)  0 1/139 (0.72%)  1
Rib fracture  0/153 (0.00%)  0 1/139 (0.72%)  1
Skin abrasion  2/153 (1.31%)  2 0/139 (0.00%)  0
Skin tear  1/153 (0.65%)  1 0/139 (0.00%)  0
Spinal epidural hematoma  0/153 (0.00%)  0 1/139 (0.72%)  1
Subdural hemorrhage  0/153 (0.00%)  0 1/139 (0.72%)  1
Tibia fracture  0/153 (0.00%)  0 1/139 (0.72%)  1
Tracheostomy malfunction  1/153 (0.65%)  1 0/139 (0.00%)  0
Wound  1/153 (0.65%)  1 0/139 (0.00%)  0
Investigations     
ALT increased  1/153 (0.65%)  1 2/139 (1.44%)  2
APTT decreased  0/153 (0.00%)  0 1/139 (0.72%)  1
APTT prolonged  1/153 (0.65%)  1 0/139 (0.00%)  0
AST increased  1/153 (0.65%)  1 4/139 (2.88%)  5
Abnormal EEG  4/153 (2.61%)  4 4/139 (2.88%)  4
Albumin decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Albumin low  1/153 (0.65%)  1 0/139 (0.00%)  0
Amino acid level decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Amylase high  0/153 (0.00%)  0 1/139 (0.72%)  1
Amylase increased  4/153 (2.61%)  4 2/139 (1.44%)  3
Arterial blood pH decreased  0/153 (0.00%)  0 1/139 (0.72%)  1
Arterial oxygen saturation decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Aspartate aminotransferase increased  0/153 (0.00%)  0 1/139 (0.72%)  1
B-type natriuretic peptide  0/153 (0.00%)  0 1/139 (0.72%)  1
BUN increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Bacteria blood identified  0/153 (0.00%)  0 1/139 (0.72%)  1
Band neutrophil count increased  2/153 (1.31%)  2 1/139 (0.72%)  1
Base excess decreased  1/153 (0.65%)  1 3/139 (2.16%)  3
Base excess increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood alkaline phosphatase decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood amino acid level increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood bicarbonate decreased  1/153 (0.65%)  1 1/139 (0.72%)  1
Blood bicarbonate increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood bicarbonate low  0/153 (0.00%)  0 2/139 (1.44%)  2
Blood creatine phosphokinase increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood culture positive  6/153 (3.92%)  6 5/139 (3.60%)  6
Blood culture positive viral  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood gases abnormal  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood in urine  2/153 (1.31%)  2 0/139 (0.00%)  0
Blood lactic acid increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Blood osmolarity increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Blood pH abnormal  0/153 (0.00%)  0 1/139 (0.72%)  1
Blood phosphorus increased  1/153 (0.65%)  1 1/139 (0.72%)  1
Blood pressure increased  1/153 (0.65%)  1 1/139 (0.72%)  1
Bronchoalveolar lavage abnormal  1/153 (0.65%)  1 0/139 (0.00%)  0
C-reactive protein increased  1/153 (0.65%)  1 0/139 (0.00%)  0
CK increased  2/153 (1.31%)  2 0/139 (0.00%)  0
CO2 total abnormal  2/153 (1.31%)  2 1/139 (0.72%)  1
CPK increase  0/153 (0.00%)  0 1/139 (0.72%)  1
CRP increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Calcium decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Capillary nail refill test abnormal  2/153 (1.31%)  3 0/139 (0.00%)  0
Carboxyhemoglobin increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Cardiac enzymes increased  3/153 (1.96%)  3 0/139 (0.00%)  0
Cardiac output decreased  2/153 (1.31%)  2 0/139 (0.00%)  0
Chloride increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Chloride low  0/153 (0.00%)  0 1/139 (0.72%)  1
Clotting time increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Coagulation time prolonged  1/153 (0.65%)  1 0/139 (0.00%)  0
Cortisol low  1/153 (0.65%)  1 0/139 (0.00%)  0
Creatine kinase increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Creatine phosphokinase increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Creatinine increased  1/153 (0.65%)  1 2/139 (1.44%)  3
Decreased hemoglobin  2/153 (1.31%)  2 1/139 (0.72%)  1
Decreased ventricular afterload  0/153 (0.00%)  0 1/139 (0.72%)  1
Drug level above therapeutic  0/153 (0.00%)  0 1/139 (0.72%)  1
ECG P wave inverted  1/153 (0.65%)  1 0/139 (0.00%)  0
EEG abnormal  0/153 (0.00%)  0 4/139 (2.88%)  4
Elevated liver enzymes  2/153 (1.31%)  2 1/139 (0.72%)  1
End-tidal CO2 decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Fecal occult blood  0/153 (0.00%)  0 1/139 (0.72%)  1
Function pulmonary decreased  0/153 (0.00%)  0 1/139 (0.72%)  1
Gastric pH decreased  0/153 (0.00%)  0 1/139 (0.72%)  1
Glucose decreased  1/153 (0.65%)  1 1/139 (0.72%)  1
Glucose high  0/153 (0.00%)  0 2/139 (1.44%)  2
Glucose increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Glucose urine present  0/153 (0.00%)  0 1/139 (0.72%)  1
HIE  1/153 (0.65%)  1 1/139 (0.72%)  1
Haemoglobin low  2/153 (1.31%)  3 4/139 (2.88%)  4
Heart rate decreased  2/153 (1.31%)  3 0/139 (0.00%)  0
Heart rate increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Hematocrit decreased  1/153 (0.65%)  1 1/139 (0.72%)  1
Hematocrit low  0/153 (0.00%)  0 1/139 (0.72%)  1
Hemoglobin decreased  1/153 (0.65%)  1 1/139 (0.72%)  1
INR decreased  0/153 (0.00%)  0 1/139 (0.72%)  1
INR increased  0/153 (0.00%)  0 2/139 (1.44%)  2
Increased blood pressure  1/153 (0.65%)  1 2/139 (1.44%)  2
Influenza antibody test positive  1/153 (0.65%)  1 0/139 (0.00%)  0
Ionized calcium decreased  1/153 (0.65%)  1 1/139 (0.72%)  1
LDH decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
LDH increased  1/153 (0.65%)  1 3/139 (2.16%)  3
Lactate dehydrogenase increased  4/153 (2.61%)  5 6/139 (4.32%)  6
Lactate high  0/153 (0.00%)  0 1/139 (0.72%)  1
Lactate increased  3/153 (1.96%)  3 1/139 (0.72%)  1
Lipase increased  3/153 (1.96%)  3 2/139 (1.44%)  2
Liver function tests raised  1/153 (0.65%)  1 0/139 (0.00%)  0
Magnesium decreased  1/153 (0.65%)  1 1/139 (0.72%)  1
Magnesium increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Magnesium low  1/153 (0.65%)  1 0/139 (0.00%)  0
Methicillin-resistant Staphylococcus aureus test positive  1/153 (0.65%)  1 1/139 (0.72%)  1
Neurological examination abnormal  0/153 (0.00%)  0 1/139 (0.72%)  1
Nitrite urine present  1/153 (0.65%)  1 0/139 (0.00%)  0
Oxygen saturation decreased  11/153 (7.19%)  12 8/139 (5.76%)  8
PCO2 abnormal  0/153 (0.00%)  0 1/139 (0.72%)  1
PCO2 elevated  2/153 (1.31%)  2 0/139 (0.00%)  0
PCO2 increased  0/153 (0.00%)  0 1/139 (0.72%)  1
PO2 decreased  1/153 (0.65%)  1 3/139 (2.16%)  3
PO2 increased  1/153 (0.65%)  1 0/139 (0.00%)  0
PT increased  1/153 (0.65%)  1 1/139 (0.72%)  1
PTT prolonged  0/153 (0.00%)  0 1/139 (0.72%)  1
Peripheral pulse decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Phosphate increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Phosphorus low  0/153 (0.00%)  0 1/139 (0.72%)  1
Platelet count increased  0/153 (0.00%)  0 1/139 (0.72%)  1
Potassium decreased  2/153 (1.31%)  2 5/139 (3.60%)  5
Potassium increased  1/153 (0.65%)  1 1/139 (0.72%)  1
Prealbumin  1/153 (0.65%)  1 0/139 (0.00%)  0
Procalcitonin increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Prothrombin time prolonged  1/153 (0.65%)  1 0/139 (0.00%)  0
QT prolonged  3/153 (1.96%)  3 0/139 (0.00%)  0
Raised LFTs  2/153 (1.31%)  2 0/139 (0.00%)  0
Respiratory sounds decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
ST segment depression  1/153 (0.65%)  1 0/139 (0.00%)  0
Sodium increased  1/153 (0.65%)  1 1/139 (0.72%)  1
Sodium low  0/153 (0.00%)  0 2/139 (1.44%)  2
Sputum culture positive  16/153 (10.46%)  21 12/139 (8.63%)  15
SvO2 decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
Transaminitis  3/153 (1.96%)  3 1/139 (0.72%)  1
Troponin increased  1/153 (0.65%)  1 3/139 (2.16%)  3
Urine culture positive  9/153 (5.88%)  11 6/139 (4.32%)  7
Urine ketone body present  0/153 (0.00%)  0 1/139 (0.72%)  1
Urine output decreased  7/153 (4.58%)  8 8/139 (5.76%)  8
Urine output increased  1/153 (0.65%)  1 4/139 (2.88%)  4
WBC decreased  3/153 (1.96%)  3 0/139 (0.00%)  0
WBC increased  1/153 (0.65%)  1 1/139 (0.72%)  1
pH decreased  1/153 (0.65%)  1 0/139 (0.00%)  0
pH increased  1/153 (0.65%)  1 0/139 (0.00%)  0
Metabolism and nutrition disorders     
Acidosis  6/153 (3.92%)  6 3/139 (2.16%)  3
Acidosis metabolic  0/153 (0.00%)  0 1/139 (0.72%)  1
Alkalosis  1/153 (0.65%)  1 1/139 (0.72%)  1
Cerebral salt-wasting syndrome  0/153 (0.00%)  0 3/139 (2.16%)  3
Feeding difficulties and mismanagement  0/153 (0.00%)  0 1/139 (0.72%)  1
Fluid imbalance  1/153 (0.65%)  1 0/139 (0.00%)  0
Fluid overload  4/153 (2.61%)  4 3/139 (2.16%)  3
Fluid retention  1/153 (0.65%)  1 0/139 (0.00%)  0
Hyperammonaemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Hyperammonemia  1/153 (0.65%)  1 1/139 (0.72%)  1
Hyperamylasemia  0/153 (0.00%)  0 1/139 (0.72%)  1
Hypercalcemia  1/153 (0.65%)  1 0/139 (0.00%)  0
Hyperchloremia  2/153 (1.31%)  2 4/139 (2.88%)  4
Hypercholesterolemia  0/153 (0.00%)  0 1/139 (0.72%)  1
Hyperglycemia  15/153 (9.80%)  16 16/139 (11.51%)  16
Hyperkalemia  3/153 (1.96%)  3 7/139 (5.04%)  7
Hyperlipasemia  0/153 (0.00%)  0 1/139 (0.72%)  1
Hypermagnesemia  1/153 (0.65%)  1 1/139 (0.72%)  1
Hypernatremia  12/153 (7.84%)  12 13/139 (9.35%)  14
Hyperphosphatemia  4/153 (2.61%)  4 2/139 (1.44%)  2
Hypoalbuminemia  4/153 (2.61%)  4 2/139 (1.44%)  2
Hypocalcemia  15/153 (9.80%)  15 11/139 (7.91%)  11
Hypochloremia  1/153 (0.65%)  1 2/139 (1.44%)  2
Hypoglycemia  11/153 (7.19%)  11 12/139 (8.63%)  12
Hypokalemia  35/153 (22.88%)  37 19/139 (13.67%)  20
Hypomagnesemia  12/153 (7.84%)  12 6/139 (4.32%)  6
Hyponatremia  8/153 (5.23%)  9 8/139 (5.76%)  8
Hypophosphatemia  7/153 (4.58%)  7 6/139 (4.32%)  7
Hypoproteinemia  2/153 (1.31%)  2 1/139 (0.72%)  1
Hypovolemia  3/153 (1.96%)  3 0/139 (0.00%)  0
Lactic acidosis  4/153 (2.61%)  4 0/139 (0.00%)  0
Metabolic acidosis  10/153 (6.54%)  10 3/139 (2.16%)  4
Metabolic alkalosis  0/153 (0.00%)  0 2/139 (1.44%)  2
Volume overload  1/153 (0.65%)  1 0/139 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle spasms  0/153 (0.00%)  0 1/139 (0.72%)  1
Neck rigidity  1/153 (0.65%)  1 0/139 (0.00%)  0
Rhabdomyolysis  2/153 (1.31%)  2 0/139 (0.00%)  0
Spasms  1/153 (0.65%)  1 0/139 (0.00%)  0
Twitching  1/153 (0.65%)  1 0/139 (0.00%)  0
Twitching of limbs  1/153 (0.65%)  1 0/139 (0.00%)  0
Weakness in extremity  1/153 (0.65%)  1 0/139 (0.00%)  0
Nervous system disorders     
Anoxic brain damage  0/153 (0.00%)  0 2/139 (1.44%)  2
Autonomic dysfunction  0/153 (0.00%)  0 1/139 (0.72%)  1
Autonomic instability  0/153 (0.00%)  0 1/139 (0.72%)  1
Brain injury  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral dysfunction  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral edema  5/153 (3.27%)  5 3/139 (2.16%)  3
Cerebral hematoma  0/153 (0.00%)  0 1/139 (0.72%)  1
Cerebral hemorrhage  1/153 (0.65%)  1 0/139 (0.00%)  0
Cerebral infarct  0/153 (0.00%)  0 1/139 (0.72%)  1
Cerebral infarction  0/153 (0.00%)  0 1/139 (0.72%)  1
Cerebral ischemia  0/153 (0.00%)  0 1/139 (0.72%)  1
Clonus  2/153 (1.31%)  2 1/139 (0.72%)  1
Drooling  1/153 (0.65%)  1 0/139 (0.00%)  0
Dysautonomia  1/153 (0.65%)  1 3/139 (2.16%)  3
Encephalopathy  3/153 (1.96%)  3 1/139 (0.72%)  1
Fasciculation  1/153 (0.65%)  1 0/139 (0.00%)  0
Headache  1/153 (0.65%)  1 0/139 (0.00%)  0
Hypertonia  2/153 (1.31%)  2 1/139 (0.72%)  1
Hypotonia  0/153 (0.00%)  0 1/139 (0.72%)  1
Hypoxic brain damage  6/153 (3.92%)  6 2/139 (1.44%)  2
Hypoxic encephalopathy  3/153 (1.96%)  4 7/139 (5.04%)  7
IIIrd nerve palsy  0/153 (0.00%)  0 1/139 (0.72%)  1
Increased intracranial pressure  0/153 (0.00%)  0 1/139 (0.72%)  1
Ischemic stroke  0/153 (0.00%)  0 1/139 (0.72%)  1
Leg spasticity  1/153 (0.65%)  1 0/139 (0.00%)  0
Memory deficit  0/153 (0.00%)  0 1/139 (0.72%)  1
Movements abnormal  1/153 (0.65%)  1 0/139 (0.00%)  0
Myoclonic jerks  2/153 (1.31%)  2 0/139 (0.00%)  0
Myoclonic seizure NOS  0/153 (0.00%)  0 1/139 (0.72%)  1
Myoclonus  3/153 (1.96%)  3 1/139 (0.72%)  1
Nystagmus  2/153 (1.31%)  2 0/139 (0.00%)  0
Periventricular leukomalacia  1/153 (0.65%)  1 0/139 (0.00%)  0
Quadriparesis  2/153 (1.31%)  2 0/139 (0.00%)  0
Seizure  22/153 (14.38%)  26 14/139 (10.07%)  15
Seizures  20/153 (13.07%)  21 16/139 (11.51%)  17
Shaking  2/153 (1.31%)  2 1/139 (0.72%)  1
Short-term memory impairment  1/153 (0.65%)  1 0/139 (0.00%)  0
Spasticity  1/153 (0.65%)  1 0/139 (0.00%)  0
Status epilepticus  2/153 (1.31%)  2 3/139 (2.16%)  3
Stroke  1/153 (0.65%)  1 0/139 (0.00%)  0
Thalamic syndrome  9/153 (5.88%)  9 6/139 (4.32%)  6
Tremor  0/153 (0.00%)  0 2/139 (1.44%)  2
Tremor limb  1/153 (0.65%)  1 0/139 (0.00%)  0
Vocal cord paresis  1/153 (0.65%)  1 0/139 (0.00%)  0
Psychiatric disorders     
Agitation  14/153 (9.15%)  14 5/139 (3.60%)  5
Delirium  1/153 (0.65%)  1 0/139 (0.00%)  0
Hallucinations  1/153 (0.65%)  1 0/139 (0.00%)  0
Insomnia  1/153 (0.65%)  1 0/139 (0.00%)  0
Posturing  0/153 (0.00%)  0 3/139 (2.16%)  3
Withdrawal syndrome  2/153 (1.31%)  2 0/139 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  2/153 (1.31%)  2 0/139 (0.00%)  0
Acute renal failure  1/153 (0.65%)  1 1/139 (0.72%)  1
Acute renal insufficiency  1/153 (0.65%)  1 0/139 (0.00%)  0
Anuria  0/153 (0.00%)  0 1/139 (0.72%)  1
Azotemia  1/153 (0.65%)  1 1/139 (0.72%)  1
Hematuria  2/153 (1.31%)  2 0/139 (0.00%)  0
Neurogenic bladder  2/153 (1.31%)  2 0/139 (0.00%)  0
Oliguria  0/153 (0.00%)  0 1/139 (0.72%)  2
Polyuria  1/153 (0.65%)  1 1/139 (0.72%)  1
Renal failure  1/153 (0.65%)  1 1/139 (0.72%)  1
Renal function aggravated  0/153 (0.00%)  0 1/139 (0.72%)  1
Renal function disorder  1/153 (0.65%)  1 0/139 (0.00%)  0
Renal insufficiency  4/153 (2.61%)  4 0/139 (0.00%)  0
Urinary retention  1/153 (0.65%)  1 2/139 (1.44%)  2
Reproductive system and breast disorders     
Cervix edema  1/153 (0.65%)  1 0/139 (0.00%)  0
Genital swelling  1/153 (0.65%)  1 0/139 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
ARDS  2/153 (1.31%)  2 1/139 (0.72%)  1
Acquired tracheobronchomalacia  0/153 (0.00%)  0 1/139 (0.72%)  1
Acute respiratory failure  1/153 (0.65%)  1 0/139 (0.00%)  0
Airway secretion excessive  1/153 (0.65%)  1 0/139 (0.00%)  0
Apnea  1/153 (0.65%)  1 2/139 (1.44%)  2
Aspiration  0/153 (0.00%)  0 2/139 (1.44%)  2
Aspiration pneumonia  1/153 (0.65%)  1 1/139 (0.72%)  1
Asthma aggravated  1/153 (0.65%)  1 0/139 (0.00%)  0
Atelectasis  10/153 (6.54%)  12 16/139 (11.51%)  22
Bleeding nose  1/153 (0.65%)  1 0/139 (0.00%)  0
Breathing abnormally shallow  1/153 (0.65%)  1 2/139 (1.44%)  2
Bronchial secretion excessive  1/153 (0.65%)  1 0/139 (0.00%)  0
Bronchial wall thickening  0/153 (0.00%)  0 1/139 (0.72%)  1
Chronic respiratory failure  0/153 (0.00%)  0 1/139 (0.72%)  1
Cough  2/153 (1.31%)  2 0/139 (0.00%)  0
Coughing  0/153 (0.00%)  0 1/139 (0.72%)  1
Diaphragmatic hernia  0/153 (0.00%)  0 1/139 (0.72%)  1
Dyspnea  1/153 (0.65%)  1 0/139 (0.00%)  0
Emphysema  0/153 (0.00%)  0 1/139 (0.72%)  1
Hypercapnia  2/153 (1.31%)  2 1/139 (0.72%)  1
Hypercarbia  3/153 (1.96%)  3 1/139 (0.72%)  1
Hyperventilation  1/153 (0.65%)  1 0/139 (0.00%)  0
Hypoxemia  5/153 (3.27%)  5 3/139 (2.16%)  3
Hypoxia  3/153 (1.96%)  4 2/139 (1.44%)  2
Increased bronchial secretion  1/153 (0.65%)  1 0/139 (0.00%)  0
Increased upper airway secretion  1/153 (0.65%)  1 0/139 (0.00%)  0
Interstitial lung disease  0/153 (0.00%)  0 1/139 (0.72%)  1
Labored breathing  0/153 (0.00%)  0 1/139 (0.72%)  1
Lung disease  1/153 (0.65%)  1 0/139 (0.00%)  0
Lung hyperinflation  1/153 (0.65%)  1 0/139 (0.00%)  0
Lung infiltration  1/153 (0.65%)  1 0/139 (0.00%)  0
Nasal discharge  2/153 (1.31%)  2 0/139 (0.00%)  0
Pharyngeal edema  0/153 (0.00%)  0 1/139 (0.72%)  1
Pleural effusion  16/153 (10.46%)  16 11/139 (7.91%)  13
Pneumomediastinum  5/153 (3.27%)  5 5/139 (3.60%)  5
Pneumothorax  6/153 (3.92%)  6 6/139 (4.32%)  6
Pulmonary edema  12/153 (7.84%)  12 6/139 (4.32%)  6
Pulmonary edema recurrent  0/153 (0.00%)  0 1/139 (0.72%)  1
Pulmonary hemorrhage  1/153 (0.65%)  1 1/139 (0.72%)  1
Pulmonary hypertension  1/153 (0.65%)  1 1/139 (0.72%)  1
Pulmonary vascular disorder  0/153 (0.00%)  0 1/139 (0.72%)  1
Respiratory acidosis  4/153 (2.61%)  4 2/139 (1.44%)  2
Respiratory alkalosis  1/153 (0.65%)  1 2/139 (1.44%)  2
Respiratory distress  3/153 (1.96%)  3 4/139 (2.88%)  4
Respiratory failure  0/153 (0.00%)  0 1/139 (0.72%)  1
Respiratory insufficiency  1/153 (0.65%)  1 1/139 (0.72%)  1
Retention carbon dioxide  1/153 (0.65%)  1 0/139 (0.00%)  0
Stridor  2/153 (1.31%)  2 0/139 (0.00%)  0
Subglottic edema  1/153 (0.65%)  1 0/139 (0.00%)  0
Tachypnea  3/153 (1.96%)  3 4/139 (2.88%)  4
Unspecified disease of respiratory system  0/153 (0.00%)  0 1/139 (0.72%)  1
Upper airway obstruction  1/153 (0.65%)  1 0/139 (0.00%)  0
Wheezing  1/153 (0.65%)  1 1/139 (0.72%)  1
Wheezing aggravated  0/153 (0.00%)  0 1/139 (0.72%)  1
Skin and subcutaneous tissue disorders     
Blister  1/153 (0.65%)  1 0/139 (0.00%)  0
Blisters  2/153 (1.31%)  2 1/139 (0.72%)  1
Diaper rash  1/153 (0.65%)  1 1/139 (0.72%)  1
Ecchymosis  1/153 (0.65%)  1 0/139 (0.00%)  0
Facial swelling  1/153 (0.65%)  1 0/139 (0.00%)  0
Macular rash  1/153 (0.65%)  1 0/139 (0.00%)  0
Mottled skin  1/153 (0.65%)  1 0/139 (0.00%)  0
Petechia  1/153 (0.65%)  1 0/139 (0.00%)  0
Pressure sore  1/153 (0.65%)  1 0/139 (0.00%)  0
Pruritis  1/153 (0.65%)  1 0/139 (0.00%)  0
Rash  1/153 (0.65%)  1 1/139 (0.72%)  1
Red man syndrome  0/153 (0.00%)  0 1/139 (0.72%)  1
Redness  2/153 (1.31%)  2 1/139 (0.72%)  1
Skin breakdown  4/153 (2.61%)  7 4/139 (2.88%)  4
Skin fissure  1/153 (0.65%)  1 0/139 (0.00%)  0
Skin irritation  1/153 (0.65%)  1 0/139 (0.00%)  0
Skin lesion  1/153 (0.65%)  1 0/139 (0.00%)  0
Skin rash  1/153 (0.65%)  2 0/139 (0.00%)  0
Skin ulcer  1/153 (0.65%)  1 0/139 (0.00%)  0
Subcutaneous emphysema  2/153 (1.31%)  2 1/139 (0.72%)  1
Ulcer skin  0/153 (0.00%)  0 1/139 (0.72%)  1
Vascular disorders     
Acute hypotension  0/153 (0.00%)  0 2/139 (1.44%)  2
Aortic dilatation  1/153 (0.65%)  1 0/139 (0.00%)  0
Aortic thrombosis  0/153 (0.00%)  0 1/139 (0.72%)  1
Blood pressure fluctuation  0/153 (0.00%)  0 1/139 (0.72%)  1
Clot blood  0/153 (0.00%)  0 1/139 (0.72%)  1
Cold feet  1/153 (0.65%)  1 0/139 (0.00%)  0
Coldness of lower extremities  0/153 (0.00%)  0 1/139 (0.72%)  1
DVT  1/153 (0.65%)  1 1/139 (0.72%)  1
DVT of legs  0/153 (0.00%)  0 1/139 (0.72%)  1
Deep vein thrombosis leg  0/153 (0.00%)  0 1/139 (0.72%)  1
Femoral artery occlusion  1/153 (0.65%)  1 0/139 (0.00%)  0
Femoral artery thrombosis  1/153 (0.65%)  1 0/139 (0.00%)  0
Flushed  1/153 (0.65%)  1 0/139 (0.00%)  0
Hematoma  1/153 (0.65%)  1 0/139 (0.00%)  0
Hemodynamic instability  0/153 (0.00%)  0 2/139 (1.44%)  2
Hypertension  16/153 (10.46%)  17 18/139 (12.95%)  18
Hypertensive  2/153 (1.31%)  2 0/139 (0.00%)  0
Hypotension  49/153 (32.03%)  55 23/139 (16.55%)  23
Hypotension aggravated  2/153 (1.31%)  2 0/139 (0.00%)  0
Hypotensive  3/153 (1.96%)  3 1/139 (0.72%)  1
Jugular vein thrombosis  0/153 (0.00%)  0 1/139 (0.72%)  1
Low blood pressure  0/153 (0.00%)  0 4/139 (2.88%)  4
Phlebitis  0/153 (0.00%)  0 1/139 (0.72%)  1
Poor peripheral perfusion  1/153 (0.65%)  1 1/139 (0.72%)  1
Shock  0/153 (0.00%)  0 2/139 (1.44%)  2
Shock vascular  0/153 (0.00%)  0 1/139 (0.72%)  1
Thrombosis leg  0/153 (0.00%)  0 1/139 (0.72%)  1
Venous thrombosis  1/153 (0.65%)  1 1/139 (0.72%)  1
1
Term from vocabulary, MedDRA (13.0)
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
Layout table for Results Point of Contact information
Name/Title: Marianne Gildea, BSN, MS; Director of THAPCA Trials
Organization: University of Utah
Phone: 801-608-4907
EMail: marianne.gildea@hsc.utah.edu
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Frank W. Moler, M.D, M.S, University of Michigan
ClinicalTrials.gov Identifier: NCT00878644    
Other Study ID Numbers: 619
U01HL094339 ( U.S. NIH Grant/Contract )
First Submitted: April 8, 2009
First Posted: April 9, 2009
Results First Submitted: May 24, 2017
Results First Posted: September 29, 2017
Last Update Posted: September 29, 2017