Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-IH [In Hospital] Trial
Sponsor
University of Michigan (Other)
Overall Status
Completed
CT.gov ID
NCT00880087
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
329
33
2
77
10
0.1
Study Details
Study Description
Brief Summary
Cardiac arrest is a sudden, unexpected loss of heart function. Therapeutic hypothermia, in which the body's temperature is lowered and maintained several degrees below normal for a period of time, has been used to successfully treat adults who have experienced cardiac arrest. This study will evaluate the efficacy of therapeutic hypothermia at increasing survival rates and reducing the risk of brain injury in infants and children who experience a cardiac arrest while in the hospital.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Cardiac arrest occurs when the heart suddenly stops beating and blood flow to the body is halted. It can occur while people are in the hospital because of a medical condition or while people are out of the hospital as a result of an accident or other cause. Cardiac arrest is a serious event that is associated with high rates of death and long-term disability. When a person experiences cardiac arrest,insufficient amount of blood flow and oxygen can result in brain injury.
Therapeutic hypothermia is a therapy that involves a controlled lowering of the body temperature and then maintenance of this lower temperature for a period of time. Therapeutic hypothermia has been successfully used in adults who experience cardiac arrest to improve survival rates and health outcomes, and it has also been studied in newborn infants who have suffered from perinatal asphyxia. The purpose of this study is to evaluate the efficacy of therapeutic hypothermia at improving survival rates and reducing brain injury in infants and children who experience cardiac arrest while in the hospital.
Study researchers will conduct this study in collaboration with the following two pediatric clinical research networks: the Pediatric Emergency Care Applied Research Network (PECARN), funded by the Emergency Medical Services for Children (EMSC) program, and the National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN).
The study will enroll infants and children who have suffered a cardiac arrest while in the hospital. Randomization must occur within 6 hours of return of spontaneous circulation. Participants will be randomly assigned to receive either therapeutic hypothermia or therapeutic normothermia. Participants receiving therapeutic hypothermia will have their body temperature reduced to between 32° and 34° Celsius (C) and will remain at this temperature for 2 days. Their body temperature will then be slowly increased to the normal temperature of 36° to 37.5° C, which will be maintained until 5 days after the cardiac arrest. Participants receiving therapeutic normothermia will have their normal temperature maintained between 36° and 37.5° C for 5 days after the cardiac arrest. Special temperature control blankets will be placed to maintain their body temperature in the assigned range. After 5 days, each participant's temperature will be managed by their medical care team.
While participants are in the hospital, they will undergo frequent blood and urine collections, chest x-rays, and temperature measurements; parents of participants will complete questionnaires. When participants are ready to leave the hospital, study researchers will perform a physical and functional assessment. Twenty-eight days after the cardiac arrest, researchers will contact parents of participants to gather information on the participants' health and medical condition. At Months 3 and 12, a child development expert will contact parents to gather medical information. At Month 12, participants will attend a study visit for a neurologic examination and testing with a psychologist trained in rehabilitation.
Study Design
Study Type:
Interventional
Actual Enrollment
:
329 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Therapeutic Hypothermia After Pediatric Cardiac Arrest (In Hospital)
Study Start Date
:
Sep 1, 2009
Actual Primary Completion Date
:
Feb 1, 2016
Actual Study Completion Date
:
Feb 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Therapeutic Hypothermia Participants will receive therapeutic hypothermia after experiencing cardiac arrest. |
Procedure: Therapeutic Hypothermia
Participants who are assigned to receive therapeutic 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.
|
| Active Comparator: Therapeutic Normothermia Participants will receive therapeutic normothermia after experiencing cardiac arrest. |
Procedure: 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.
|
Outcome Measures
Primary Outcome Measures
- Survival With Good Neurobehavioral Outcome [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.]
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. Higher values of VABS-II represent a better outcome.
Secondary Outcome Measures
- Survival [Measured at one-year anniversary of cardiac arrest.]
Survival at one year after cardiac arrest
- Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest [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.]
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. Since higher levels of VABS-II represent a better outcome, a larger decline (large negative magnitude of change) in VABS-II score from baseline to one year represents a worse outcome.
- Neuropsychological Scores (for Participants Who Survive) [Measured at Month 12]
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.
Other Outcome Measures
- Neurological Abnormality Scores (for Participants Who Survive) [Measured at Month 12]
Eligibility Criteria
Criteria
Ages Eligible for Study:
48 Hours
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patient suffered cardiac arrest requiring chest compressions for at least 2 minutes (120 seconds) with ROSC/ROC; AND
-
Age greater than 48 hours (with a corrected gestational age of at least 38 weeks) and less than 18 years; AND
-
Patient requires continuous mechanical ventilation; AND
-
The cardiac arrest was unplanned (i.e., not part of cardiac surgical procedure)
Exclusion Criteria:
-
The parent or legal guardian does not speak English or Spanish (the only two languages in which VABS II is standardized)
-
Randomization is impossible within six hours of ROSC; OR
-
Patient is on extracorporeal membrane oxygenation (ECMO) when arrest occurs; OR
-
Continuous infusion of epinephrine or norepinephrine at very high doses (≥2 ug/kg/minute) received immediately prior to randomization; OR Glasgow Coma Scale motor response of five (localizing pain or for infants less than two years, withdraws to touch) or six (obeys commands, or for infants, normal spontaneous movement) prior to randomization; OR
-
History of a prior cardiac arrest with chest compressions for at least two minutes during the current hospitalization but outside the 6 hour window for randomization; OR
-
Pre-existing terminal illness with life expectancy < 12 months; OR
-
Lack of commitment to aggressive intensive care therapies including do not resuscitate orders and other limitations to care; OR
-
Cardiac arrest was associated with severe brain, thoracic, or abdominal trauma; OR
-
Active and refractory severe bleeding prior to randomization; OR
-
Near drowning in ice water with patient core temperature ≤32 °C on presentation; OR
-
Patient is pregnant; OR
-
Patient participation in a concurrent interventional trial whose protocol, in the judgment of the THAPCA investigators, prevents effective application of one or both THAPCA therapeutic treatment arms, or otherwise significantly interferes with carrying out the THAPCA protocol; OR
-
Patient is newborn with acute birth asphyxia; OR
_ Patient cared for in a neonatal intensive care unit (NICU) after arrest (ie, would not be admitted to PICU); OR
-
Patient has sickle cell anemia; OR
-
Patient known to have pre-existing cryoglobulinemia; OR
-
Central nervous system tumor with ongoing chemotherapy or radiation therapy; OR
-
Chronic hypothermia secondary to hypovolemic, pituitary, or related condition for which body temperature is consistently below 37 °C ; OR progressive degenerative encephalopathy; OR
-
Any condition in which direct skin surface cooling would be contraindicated, such as large burns, decubitus ulcers, cellulitis, or other conditions with disrupted skin integrity (NOTE: patients with open chest CPR should be included but placement of cooling mattresses will be modified as needed); OR
-
Previous enrollment in the THAPCA Trials.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital of Alabama | Birmingham | Alabama | United States | 35233 |
| 2 | Phoenix Children's Hospital | Phoenix | Arizona | United States | 85016 |
| 3 | Loma Linda University Children's Hospital | Loma Linda | California | United States | 92354 |
| 4 | Children's Hospital of Los Angeles | Los Angeles | California | United States | 90028 |
| 5 | University of California, Los Angeles | Los Angeles | California | United States | 90095 |
| 6 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
| 7 | University of California San Francisco | San Francisco | California | United States | 94143 |
| 8 | Children's National Medical Center | Washington | District of Columbia | United States | 20010 |
| 9 | Children's Hospital of Atlanta/Emory University | Atlanta | Georgia | United States | 30306 |
| 10 | Riley Children's Hospital | Indianapolis | Indiana | United States | 46202 |
| 11 | Kosair Children's Hospital | Louisville | Kentucky | United States | 40202 |
| 12 | Johns Hopkins Hospital | Baltimore | Maryland | United States | 21287 |
| 13 | University of Michigan, Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
| 14 | Children's Hospital of Michigan | Detroit | Michigan | United States | 48201 |
| 15 | Washington University in St. Louis | Saint Louis | Missouri | United States | 63110 |
| 16 | Duke Children's Hospital | Durham | North Carolina | United States | 27710 |
| 17 | Nationwide Children's Hospital in Columbus | Columbus | Ohio | United States | 43205 |
| 18 | Penn State Children's Hospital | Hershey | Pennsylvania | United States | 17033 |
| 19 | Children's Hospital of Philidelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 20 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
| 21 | LeBonheur Children's Hospital - University of Tennessee at Memphis | Memphis | Tennessee | United States | 38105 |
| 22 | Children's Medical Center Dallas | Dallas | Texas | United States | 75235 |
| 23 | University of Texas Health Sciences Center of San Antonio | San Antonio | Texas | United States | 78229 |
| 24 | Primary Children's Medical Center | Salt Lake City | Utah | United States | 84108 |
| 25 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 26 | The Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 27 | Birmingham Children's Hospital | Birmingham | United Kingdom | B4 6NH | |
| 28 | Bristol Royal Hospital for Children | Bristol | United Kingdom | BS2 8BJ | |
| 29 | University of Hampton | Hampton | United Kingdom | SO16 6YD | |
| 30 | Alder Hey Children's Hospital | Liverpool | United Kingdom | L12 2AP | |
| 31 | Evalina Children's at Guys's and St. Thomas' Hospital | London | United Kingdom | SE1 7EH | |
| 32 | Great Ormand Street Hospital | London | United Kingdom | WC1N 3JH | |
| 33 | Royal Manchester Children's Hospital | Manchester | United Kingdom | M13 9WL |
Sponsors and Collaborators
- University of Michigan
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Frank Moler, MD, University of Michigan
- Principal Investigator: Michael Dean, MD, University of Utah
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Frank W. Moler, M.D, M.S,
Professor of Pediatrics,
University of Michigan
ClinicalTrials.gov Identifier:
NCT00880087
Other Study ID Numbers:
- 620
- U01HL094345
First Posted:
Apr 13, 2009
Last Update Posted:
Jun 15, 2018
Last Verified:
May 1, 2018
Keywords provided by Frank W. Moler, M.D, M.S,
Professor of Pediatrics,
University of Michigan
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Therapeutic Hypothermia | Therapeutic Normothermia |
|---|---|---|
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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 | 166 | 163 |
| COMPLETED | 166 | 161 |
| NOT COMPLETED | 0 | 2 |
Baseline Characteristics
| Arm/Group Title | Therapeutic Hypothermia | Therapeutic Normothermia | Total |
|---|---|---|---|
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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 Participants | 166 | 163 | 329 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
1.4
|
0.6
|
1.0
|
| Age, Customized (Count of Participants) | |||
| < 2 yr |
97
58.4%
|
104
63.8%
|
201
61.1%
|
| 2 - <12 yr |
48
28.9%
|
35
21.5%
|
83
25.2%
|
| 12 - 17 yr |
21
12.7%
|
24
14.7%
|
45
13.7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
69
41.6%
|
64
39.3%
|
133
40.4%
|
| Male |
97
58.4%
|
99
60.7%
|
196
59.6%
|
Outcome Measures
| Title | Survival With Good Neurobehavioral Outcome |
|---|---|
| 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. Higher values of VABS-II represent a better 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. |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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. |
| Measure Participants | 133 | 124 |
| Alive with VABS-II >=70 at 1 year |
48
28.9%
|
48
29.4%
|
| Died or Alive with VABS-II <70 at 1 year |
85
51.2%
|
76
46.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Therapeutic Hypothermia, Therapeutic Normothermia |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.63 |
| Comments | ||
| 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 | -2.6 | |
| Confidence Interval |
(2-Sided) 95% -14.5 to 9.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Survival |
|---|---|
| Description | Survival at one year after cardiac arrest |
| Time Frame | Measured at one-year anniversary of cardiac arrest. |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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. |
| Measure Participants | 166 | 161 |
| Alive at 1 year |
81
48.8%
|
74
45.4%
|
| Died at 1 year |
85
51.2%
|
87
53.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Therapeutic Hypothermia, Therapeutic Normothermia |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.56 |
| Comments | ||
| 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 | 2.8 | |
| Confidence Interval |
(2-Sided) 95% -8.0 to 13.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest |
|---|---|
| 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. Since higher levels of VABS-II represent a better outcome, a larger decline (large negative magnitude of change) in VABS-II score from baseline to one year represents a worse 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. |
Outcome Measure Data
| 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 |
|---|---|---|
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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. |
| Measure Participants | 164 | 153 |
| Dead at 1 year |
85
51.2%
|
87
53.4%
|
| Lowest possible VABS-II at 1 year |
1
0.6%
|
0
0%
|
| 1-year decrease in VABS-II >30 points |
12
7.2%
|
8
4.9%
|
| 1-year decrease in VABS-II 16-30 points |
17
10.2%
|
14
8.6%
|
| 1-year decrease in VABS-II <=15 points or improved |
49
29.5%
|
44
27%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Therapeutic Hypothermia, Therapeutic Normothermia |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.70 |
| Comments | ||
| 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. | |
| Title | Neuropsychological Scores (for Participants Who Survive) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized children alive at one year with neuropsychological score available. |
| Arm/Group Title | Therapeutic Hypothermia | Therapeutic Normothermia |
|---|---|---|
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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. |
| Measure Participants | 68 | 48 |
| Lowest possible score |
18
10.8%
|
8
4.9%
|
| <70 (well below average) |
18
10.8%
|
11
6.7%
|
| 70 - 84 (below average) |
9
5.4%
|
14
8.6%
|
| 85-115 (average) |
21
12.7%
|
13
8%
|
| >115 (above average) |
2
1.2%
|
2
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Therapeutic Hypothermia, Therapeutic Normothermia |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.46 |
| Comments | ||
| 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. | |
| Title | Neurological Abnormality Scores (for Participants Who Survive) |
|---|---|
| Description | |
| Time Frame | Measured at Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| 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 patients receiving each treatment: 161 patients receiving Therapeutic Hypothermia and 160 patients receiving Therapeutic Normothermia. However, for all-cause mortality at 12 months, denominators can only include those with known 12-month vital status. Since 2 participants who received Therapeutic Normothermia were lost to follow-up at 1 year, the Therapeutic Normothermia denominator for all-cause mortality is 158 rather than 160. | |||
| Arm/Group Title | Therapeutic Hypothermia | Therapeutic Normothermia | ||
| Arm/Group Description | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Therapeutic Hypothermia: Participants who are assigned to receive therapeutic 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 82/161 (50.9%) | 84/158 (53.2%) | ||
Serious Adverse Events |
||||
| Therapeutic Hypothermia | Therapeutic Normothermia | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 85/161 (52.8%) | 91/160 (56.9%) | ||
| Blood and lymphatic system disorders | ||||
| Coagulopathy | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| DIC | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypercoagulation | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Leukocytosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac disorders | ||||
| Arrest cardiac | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Atrial fibrillation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Atrial perforation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bradycardia | 2/161 (1.2%) | 3 | 4/160 (2.5%) | 4 |
| Cardiac arrest | 18/161 (11.2%) | 20 | 16/160 (10%) | 17 |
| Cardiac failure | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Cardiac insufficiency | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Cardiac ischaemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac ischemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac tamponade | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac ventricular thrombosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cardiogenic shock | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Cardiopulmonary arrest | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cardiopulmonary failure | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Dysrhythmias | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Heart failure | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Myocardial infarction | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Myocarditis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Recurrent ventricular tachycardia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Right ventricular failure | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Supraventricular tachycardia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Tachycardia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Ventricular dysfunction | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ventricular tachycardia | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Gastrointestinal disorders | ||||
| Bowel perforation | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Hemorrhage intraabdominal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ischemia bowel | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Necrotizing enterocolitis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| General disorders | ||||
| Brain death | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Catheter site bleeding | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Clotting of extracorporeal circuit | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Extracorporeal membrane oxygenation complication | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Multi organ failure | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Multi-organ failure | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Multiple organ failure | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 3 |
| Infections and infestations | ||||
| Bacterial tracheitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Clostridium difficile infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Klebsiella pneumoniae infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Lower respiratory tract infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pneumonia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Pneumonia bacterial | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Respiratory infection | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 3 |
| Respiratory syncytial virus infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Sepsis | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Septic shock | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Tracheitis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Urinary tract infection bacterial | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Injury, poisoning and procedural complications | ||||
| Acute subdural hematoma | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Brain herniation | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Epidural hematoma | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Laceration of lung with open wound into thorax | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Subdural hematoma | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Subdural hemorrhage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Investigations | ||||
| Atrial pressure increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Blood culture positive | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Cardiac output decreased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| HIE | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Sputum culture positive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Acidosis aggravated | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hyperkalemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Compartment syndrome | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Nervous system disorders | ||||
| Anoxic brain damage | 5/161 (3.1%) | 5 | 8/160 (5%) | 8 |
| Anoxic encephalopathy | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cerebral edema | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 3 |
| Cerebral infarct | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cerebral infarction | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Cerebral ischaemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cerebral ischemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Encephalopathy | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hemorrhagic stroke | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemorrhagic transformation stroke | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypoxic brain damage | 3/161 (1.9%) | 3 | 2/160 (1.3%) | 2 |
| Hypoxic encephalopathy | 6/161 (3.7%) | 6 | 6/160 (3.8%) | 6 |
| Intracerebral hemorrhage | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Intracranial hemorrhage | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Intraventricular hemorrhage | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Ischemic stroke | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Middle cerebral artery infarct | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Middle cerebral artery stroke | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Neurological status deterioration | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Reflexes absent | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Seizure | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Status epilepticus | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Stroke | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Subarachnoid hemorrhage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Vocal cord paralysis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Renal failure | 1/161 (0.6%) | 1 | 4/160 (2.5%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic respiratory failure | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Embolism pulmonary | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypoxemia | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Pneumothorax | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pulmonary embolism | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pulmonary hemorrhage | 2/161 (1.2%) | 2 | 5/160 (3.1%) | 5 |
| Pulmonary hypertension | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Pulmonary hypertension aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Respiratory depression | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Respiratory failure | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Thoracic hemorrhage | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Vascular disorders | ||||
| Aortic rupture | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Critical limb ischemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Deep vein thrombosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Extremity necrosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypertension | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypotension | 4/161 (2.5%) | 4 | 2/160 (1.3%) | 2 |
| Hypotension aggravated | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Ischemia | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Ischemia peripheral | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Therapeutic Hypothermia | Therapeutic Normothermia | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 151/161 (93.8%) | 146/160 (91.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 10/161 (6.2%) | 10 | 9/160 (5.6%) | 9 |
| Coagulopathy | 10/161 (6.2%) | 10 | 13/160 (8.1%) | 13 |
| DIC | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Hemolysis | 4/161 (2.5%) | 4 | 3/160 (1.9%) | 3 |
| Heparin-induced thrombocytopenia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypercoagulation | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Leukocytosis | 5/161 (3.1%) | 5 | 3/160 (1.9%) | 3 |
| Leukopenia | 3/161 (1.9%) | 3 | 3/160 (1.9%) | 3 |
| Lymphopenia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Methemoglobinemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Monocytosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Neutropenia | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Splenomegaly | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Thrombocytopenia | 12/161 (7.5%) | 12 | 10/160 (6.3%) | 10 |
| Thrombocytopenia aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Thrombocytosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac disorders | ||||
| AV nodal tachycardia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Accelerated idioventricular rhythm | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Arrhythmia | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Atrial bigeminy | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Atrial fibrillation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Atrial flutter | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Atrial tachycardia | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Bradycardia | 15/161 (9.3%) | 16 | 5/160 (3.1%) | 5 |
| Cardiac failure | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Cardiac insufficiency | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac tamponade | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Cardiogenic shock | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Congestive cardiac failure aggravated | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cyanosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cyanosis peripheral | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ectopic atrial beats | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Effusion pericardial | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Extrasystoles | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Heart block | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Heart failure | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Junctional rhythm | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Junctional tachycardia | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Left ventricular dysfunction | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Left ventricular hypertrophy | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Left ventricular hypokinesia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Monomorphic ventricular tachycardia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Myocardial depression | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| PVC's | 3/161 (1.9%) | 4 | 1/160 (0.6%) | 1 |
| Pericardial effusion | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Premature atrial contraction | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Premature ventricular contractions | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Right bundle branch block | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Right ventricular dysfunction | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| SVT | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Sinus bradycardia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 2 |
| Sinus tachycardia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Supraventricular tachycardia | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Tachycardia | 3/161 (1.9%) | 3 | 6/160 (3.8%) | 7 |
| Trigeminy | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Ventricular arrhythmia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Ventricular dysfunction | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ventricular ectopics | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Ventricular fibrillation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Ventricular tachycardia | 1/161 (0.6%) | 1 | 7/160 (4.4%) | 9 |
| Congenital, familial and genetic disorders | ||||
| Antithrombin III deficiency | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Methylenetetrahydrofolate reductase deficiency | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Thyroglossal duct cyst | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 3/161 (1.9%) | 3 | 4/160 (2.5%) | 4 |
| Adrenal mass | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Diabetes insipidus | 3/161 (1.9%) | 3 | 5/160 (3.1%) | 5 |
| Eye disorders | ||||
| Eye movement disorder | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Eyelid ptosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Fixed dilated pupils | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Fixed pupils | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Scleral edema | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal compartment syndrome | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Abdominal distension | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Abdominal pain | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Absent bowel sounds | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Anal fissure | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ascites | 9/161 (5.6%) | 9 | 9/160 (5.6%) | 9 |
| Bleeding esophageal varices | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Blood stool | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Bloody diarrhea | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Bloody stool | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Constipation | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Distended abdomen | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Distended bowel | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Dysphagia | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Emesis | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Gastric bleeding | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Gastrointestinal bleeding | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hematemesis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hematochezia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ileus | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Ileus of bowel | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Lip ulcer | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Loose stools | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Mesenteric edema | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Nausea | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Necrotizing enterocolitis | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Oral hemorrhage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Oral lesion | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pancreatic insufficiency | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pancreatitis | 3/161 (1.9%) | 3 | 4/160 (2.5%) | 4 |
| Perihepatic fluid collection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Peritonitis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Swelling of tongue | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Typhlitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| UGI bleed | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ulcer lip | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| General disorders | ||||
| Anasarca | 5/161 (3.1%) | 5 | 8/160 (5%) | 8 |
| Catheter site bleeding | 11/161 (6.8%) | 12 | 9/160 (5.6%) | 9 |
| Catheter site hemorrhage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Clotting of extracorporeal circuit | 3/161 (1.9%) | 3 | 3/160 (1.9%) | 3 |
| Dependent edema | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Drug withdrawal syndrome | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Edema | 4/161 (2.5%) | 4 | 2/160 (1.3%) | 2 |
| Edema aggravated | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Edema generalized | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Edema trunk | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Edematous weight gain | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Extracorporeal membrane oxygenation complication | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Fever | 10/161 (6.2%) | 13 | 11/160 (6.9%) | 11 |
| Generalized edema | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Hyperthermia | 3/161 (1.9%) | 4 | 3/160 (1.9%) | 3 |
| Hypothermia | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Infusion site infiltration | 0/161 (0%) | 0 | 1/160 (0.6%) | 2 |
| Intermittent fever | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Multiple organ failure | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Necrosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Needle stick/puncture | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Opiate withdrawal symptoms | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pain | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Peripheral edema | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pitting edema | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pyrexial | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Shivering | 5/161 (3.1%) | 5 | 1/160 (0.6%) | 1 |
| Swelling | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Swelling arm | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Swelling of legs | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Swelling of limb | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Weakness generalized | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hepatobiliary disorders | ||||
| Acute liver failure | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Function liver abnormal | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Function liver decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hepatic insufficiency | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Hepatic ischemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hepatic shock | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hepatomegaly | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Hepatopathy | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hepatosplenomegaly | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hyperbilirubinemia | 3/161 (1.9%) | 3 | 6/160 (3.8%) | 6 |
| Ischemic hepatitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Liver failure | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Immune system disorders | ||||
| Hypogammaglobulinemia | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Infections and infestations | ||||
| Abdominal sepsis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Abscess hand | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bacterial eye infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bacterial infection due to staphylococcus aureus | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Bacterial tracheitis | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Candida albicans infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cardiac valve vegetation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cellulitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Enterobacter pneumonia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Enterococcal urinary tract infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Enterocolitis bacterial | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Escherichia coli infection | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Escherichia urinary tract infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Eye infection bacterial | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Eye infection staphylococcal | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Fungal rash | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Fungemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Gram-positive bacterial infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Herpes simplex | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Herpetic stomatitis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Infection MRSA | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Infection pseudomonas aeruginosa | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Infection respiratory | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Lung infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| MRSA wound infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Parvovirus B19 infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Perirectal abscess | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pleural infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pneumonia | 5/161 (3.1%) | 5 | 1/160 (0.6%) | 1 |
| Pneumonia due to Escherichia coli (E. Coli) | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pseudomonas infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Respiratory infection | 3/161 (1.9%) | 4 | 10/160 (6.3%) | 10 |
| Respiratory syncytial virus infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Respiratory tract infection viral | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Rhinovirus infection | 4/161 (2.5%) | 4 | 3/160 (1.9%) | 3 |
| Sepsis | 4/161 (2.5%) | 4 | 1/160 (0.6%) | 1 |
| Septic shock | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Sinus infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Sinusitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Staphylococcal infection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Streptococcal infection | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Streptococcus pneumoniae pneumonia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Thrush | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Tracheitis | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| UTI | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Urinary infection | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Urinary tract infection | 5/161 (3.1%) | 5 | 1/160 (0.6%) | 1 |
| Urinary tract infection bacterial | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Urinary tract infection fungal | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Urinary tract infection pseudomonal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ventilator associated pneumonia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Abrasions | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Bloody airway discharge | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Bronchial injury | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Bruise | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Collapse of lung | 7/161 (4.3%) | 7 | 1/160 (0.6%) | 1 |
| Ear injury | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Endotracheal reintubation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Excoriation | 2/161 (1.2%) | 3 | 1/160 (0.6%) | 1 |
| Foot injury | 1/161 (0.6%) | 2 | 0/160 (0%) | 0 |
| Injury to kidney | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Knee injury | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Laryngeal injury | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Nerve damage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Operation site bleed | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Postoperative bleeding | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Radial artery injury | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Rib fracture | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Scratch | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Shunt thrombosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Subdural hemorrhage | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Tracheostomy malfunction | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Unintended endotracheal extubation | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Wound dehiscence | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Wound oozing | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Investigations | ||||
| ALT increased | 7/161 (4.3%) | 7 | 3/160 (1.9%) | 3 |
| APTT increased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| APTT prolonged | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| AST increased | 5/161 (3.1%) | 5 | 5/160 (3.1%) | 5 |
| Abnormal EEG | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Adenovirus test positive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Albumin decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Albumin low | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Ammonia increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Amylase high | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Amylase increased | 5/161 (3.1%) | 5 | 4/160 (2.5%) | 4 |
| Antithrombin III decreased | 2/161 (1.2%) | 2 | 4/160 (2.5%) | 4 |
| Antithrombin III increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Arterial blood pH decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Arterial catheterisation abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Aspartate aminotransferase increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Atrial pressure increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| B-type natriuretic peptide | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| BNP increased | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| BUN increased | 2/161 (1.2%) | 2 | 6/160 (3.8%) | 6 |
| Bacteria sputum identified | 1/161 (0.6%) | 2 | 0/160 (0%) | 0 |
| Bacteria stool identified | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Bacteria urine identified | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Band neutrophil count increased | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Base excess abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Base excess decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Base excess increased | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Bilirubin elevated | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bilirubin increased | 6/161 (3.7%) | 6 | 3/160 (1.9%) | 3 |
| Blood LDH abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blood amylase increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blood bicarbonate decreased | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Blood bicarbonate increased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Blood bicarbonate low | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blood bilirubin decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blood culture positive | 5/161 (3.1%) | 6 | 6/160 (3.8%) | 7 |
| Blood lactic acid increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Blood phosphorus increased | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Blood potassium increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blood pressure diastolic low | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Blood sodium decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blood urea nitrogen increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Body temperature increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Brain natriuretic peptide abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Brain natriuretic peptide increased | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| C-reactive protein abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| C-reactive protein increased | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| CK increased | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| CPK increased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 2 |
| CRP increased | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Calcium ionized increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Calcium low | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Capillary nail refill test abnormal | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Carbon dioxide decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Carbon dioxide increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Carbon dioxide total decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Carbon dioxide total increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cardiac enzymes increased | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Cardiac output decreased | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 3 |
| Cardiac troponin I increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Casts urinary granular | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Central venous pressure decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Central venous pressure increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Chloride decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Chloride low | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Clotting time increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Coagulation factor II level decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Coronavirus test positive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Creatine kinase increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Creatinine high | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Creatinine increased | 2/161 (1.2%) | 2 | 6/160 (3.8%) | 6 |
| Culture throat positive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Culture wound positive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Decreased hemoglobin | 0/161 (0%) | 0 | 4/160 (2.5%) | 4 |
| Drug level in blood increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| EEG abnormal | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Elevated liver enzymes | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Fecal occult blood positive | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Fibrin D dimer increased | 4/161 (2.5%) | 4 | 0/160 (0%) | 0 |
| Fibrinogen decreased | 7/161 (4.3%) | 7 | 2/160 (1.3%) | 2 |
| Fibrinogen increased | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Free hemoglobin present | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Free plasma hemoglobin | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Glucose decreased | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Glucose high | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Glucose increased | 2/161 (1.2%) | 2 | 4/160 (2.5%) | 4 |
| HIV positive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Haemoglobin abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Haemoglobin low | 4/161 (2.5%) | 4 | 1/160 (0.6%) | 1 |
| Heart rate low | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hematocrit decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hematocrit low | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Hemoglobin decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemoglobin increased | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| INR decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 2 |
| INR increased | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Increased platelets | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Increased serum creatinine | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ionized calcium decreased | 2/161 (1.2%) | 2 | 7/160 (4.4%) | 7 |
| Ionized calcium increased | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| LDH decreased | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| LDH increased | 3/161 (1.9%) | 3 | 3/160 (1.9%) | 3 |
| LFTs raised | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Lactate blood increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Lactate dehydrogenase | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Lactate dehydrogenase increased | 13/161 (8.1%) | 13 | 5/160 (3.1%) | 5 |
| Lactate increased | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Lipase increased | 9/161 (5.6%) | 9 | 5/160 (3.1%) | 5 |
| Liver enzyme abnormal | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Liver function test abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Liver function tests raised | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Long QT | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Low pH | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Low platelets | 6/161 (3.7%) | 7 | 3/160 (1.9%) | 3 |
| Lung function abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Magnesium decreased | 5/161 (3.1%) | 5 | 5/160 (3.1%) | 5 |
| Magnesium increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Magnesium low | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Mean arterial pressure increased | 1/161 (0.6%) | 2 | 1/160 (0.6%) | 1 |
| Methicillin-resistant Staphylococcus aureus test positive | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Mycoplasma antibody positive | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Neutrophil count low | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Nonspecific ST segment change | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Occult blood positive | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Osmolality increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Oxygen saturation decreased | 4/161 (2.5%) | 5 | 12/160 (7.5%) | 12 |
| PCO2 abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| PCO2 decreased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| PCO2 elevated | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 4 |
| PO2 decreased | 0/161 (0%) | 0 | 2/160 (1.3%) | 6 |
| PT increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| PT prolonged | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| PTT prolonged | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pancreatic enzymes increased | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Peripheral pulse decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Phosphate high | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Phosphate increased | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Phosphate low | 2/161 (1.2%) | 3 | 0/160 (0%) | 0 |
| Phosphorus low | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Platelet count decreased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Platelets decreased | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Potassium decreased | 4/161 (2.5%) | 5 | 2/160 (1.3%) | 2 |
| Potassium high | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Potassium increased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Potassium low | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Prealbumin decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Procalcitonin increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Protein total decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Prothrombin time increased | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Pulse absent | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pulse pressure abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| QRS widened | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| QT interval prolonged | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| RBC decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| RDW increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Raised LFTs | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Right atrial pressure increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| SGOT increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| ST segment elevation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Serum serotonin decreased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Serum sodium decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Sodium increased | 4/161 (2.5%) | 4 | 1/160 (0.6%) | 1 |
| Sputum culture positive | 15/161 (9.3%) | 16 | 11/160 (6.9%) | 12 |
| Stool Guaiac test positive | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Thyroid stimulating hormone decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Transaminases increased | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Transaminitis | 4/161 (2.5%) | 4 | 3/160 (1.9%) | 3 |
| Tri-iodothyronine low | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Triglyceride increased | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Triglycerides high | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Troponin I increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Troponin increased | 7/161 (4.3%) | 7 | 2/160 (1.3%) | 2 |
| Urea increased | 1/161 (0.6%) | 2 | 1/160 (0.6%) | 1 |
| Urea nitrogen increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Urine culture positive | 8/161 (5%) | 8 | 6/160 (3.8%) | 7 |
| Urine output decreased | 7/161 (4.3%) | 7 | 5/160 (3.1%) | 5 |
| Urine output increased | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| VEP's abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Vascular resistance pulmonary increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Venous blood pH decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Venous oxygen saturation decreased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Viral test positive | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Viral titer increased | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| WBC decreased | 2/161 (1.2%) | 2 | 4/160 (2.5%) | 4 |
| WBC increased | 3/161 (1.9%) | 3 | 2/160 (1.3%) | 2 |
| White blood cell agglutination present | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| White blood cell count high | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| White blood cell count increased | 2/161 (1.2%) | 2 | 5/160 (3.1%) | 5 |
| White blood cell increased | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| pH increased | 2/161 (1.2%) | 4 | 3/160 (1.9%) | 3 |
| Metabolism and nutrition disorders | ||||
| Acidemia | 1/161 (0.6%) | 2 | 0/160 (0%) | 0 |
| Acidosis | 3/161 (1.9%) | 3 | 3/160 (1.9%) | 3 |
| Acidosis aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Acidosis metabolic | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Alkalosis | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Cerebral salt-wasting syndrome | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Dehydration | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Electrolyte imbalance | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Fluid imbalance | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Fluid overload | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Hyperammonemia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Hyperamylasemia | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Hypercalcemia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Hyperchloremia | 3/161 (1.9%) | 3 | 0/160 (0%) | 0 |
| Hyperglycaemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hyperglycemia | 21/161 (13%) | 21 | 20/160 (12.5%) | 20 |
| Hyperkalemia | 3/161 (1.9%) | 3 | 6/160 (3.8%) | 6 |
| Hyperlactatemia | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Hypermagnesemia | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Hypernatremia | 8/161 (5%) | 8 | 7/160 (4.4%) | 7 |
| Hyperphosphatemia | 1/161 (0.6%) | 1 | 5/160 (3.1%) | 5 |
| Hypertriglyceridemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hyperuricemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypoalbuminemia | 4/161 (2.5%) | 4 | 4/160 (2.5%) | 4 |
| Hypocalcemia | 17/161 (10.6%) | 17 | 11/160 (6.9%) | 11 |
| Hypochloremia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypoglycemia | 8/161 (5%) | 8 | 3/160 (1.9%) | 3 |
| Hypokalemia | 44/161 (27.3%) | 52 | 31/160 (19.4%) | 33 |
| Hypomagnesemia | 10/161 (6.2%) | 10 | 10/160 (6.3%) | 10 |
| Hyponatraemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hyponatremia | 6/161 (3.7%) | 6 | 4/160 (2.5%) | 4 |
| Hypophosphatemia | 10/161 (6.2%) | 10 | 7/160 (4.4%) | 7 |
| Hypoproteinemia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Hypovolemia | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Lactic acidosis | 4/161 (2.5%) | 4 | 2/160 (1.3%) | 2 |
| Metabolic acidosis | 5/161 (3.1%) | 6 | 4/160 (2.5%) | 4 |
| Metabolic alkalosis | 3/161 (1.9%) | 3 | 2/160 (1.3%) | 2 |
| Volume overload | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Compartment syndrome | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Neck mass | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Rhabdomyolysis | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Stiffness | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Weakness in extremity | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Nervous system disorders | ||||
| Anoxic brain damage | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Brain injury | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cerebral dysfunction | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Cerebral edema | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Cerebral hemorrhage | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Cerebral infarct | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Cerebral infarction | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Cerebral ischemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Choreiform | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Coma | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Convulsive movements | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Depressed level of consciousness | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Encephalopathy | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Encephalopathy acute | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Focal seizures | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemiparesis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemorrhage cerebral | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypertonia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypertonicity | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypotonia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypoxic brain damage | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Hypoxic encephalopathy | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Increased intracranial pressure | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Infarct cerebral | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Intracerebral bleed | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Intracranial hemorrhage | 1/161 (0.6%) | 1 | 4/160 (2.5%) | 4 |
| Intraventricular hemorrhage | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Ischemia cerebral | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Middle cerebral artery infarct | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Movements involuntary of limbs | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Movements reduced | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Myoclonus | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Neurological status deterioration | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Paresis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Periventricular leukomalacia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Seizure | 16/161 (9.9%) | 17 | 10/160 (6.3%) | 10 |
| Seizures | 12/161 (7.5%) | 13 | 16/160 (10%) | 17 |
| Stroke | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Subarachnoid hemorrhage | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Subependymal hemorrhage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Thalamic syndrome | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Tonic clonic movements | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Tremor | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Unresponsive | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Vocal cord paralysis | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Weakness left or right side | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Psychiatric disorders | ||||
| Agitation | 4/161 (2.5%) | 4 | 6/160 (3.8%) | 6 |
| Agitation aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Anxiety | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Anxiety aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Disorientated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Drug dependence | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hallucination | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hallucinations | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Increased agitation | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 3/161 (1.9%) | 3 | 4/160 (2.5%) | 4 |
| Acute renal failure | 4/161 (2.5%) | 4 | 1/160 (0.6%) | 1 |
| Acute renal insufficiency | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Anuria | 3/161 (1.9%) | 3 | 1/160 (0.6%) | 1 |
| Azotemia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Bladder distension | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bleeding urogenital | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Haematuria | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hematuria | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 3 |
| Hematuria aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemoglobinuria | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Oliguria | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Renal disease | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Renal failure | 5/161 (3.1%) | 5 | 2/160 (1.3%) | 2 |
| Renal failure aggravated | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Renal function abnormal | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Renal function disorder | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Renal impairment | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Renal insufficiency | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 3 |
| Uremia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Urinary retention | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Genital rash | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Paraphimosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pelvic fluid collection | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Priapism | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Scrotal edema | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| ARDS | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Acute lung injury | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Acute on chronic respiratory failure | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Acute respiratory failure | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Aspiration | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Atelectasis | 12/161 (7.5%) | 14 | 17/160 (10.6%) | 20 |
| Bronchial hemorrhage | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Emphysema | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Epistaxis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemoptysis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hemothorax | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Hypercapnia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Hypercarbia | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Hyperoxia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Hypoventilation | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypoxemia | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Hypoxia | 4/161 (2.5%) | 4 | 4/160 (2.5%) | 4 |
| Increased work of breathing | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Labored breathing | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Lobar collapse | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Lung consolidation | 1/161 (0.6%) | 2 | 0/160 (0%) | 0 |
| Lung hyperinflation | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Mediastinal hemorrhage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Necrosis of bronchioli | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Nose bleed | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Oropharyngeal hemorrhage | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pleural effusion | 18/161 (11.2%) | 21 | 17/160 (10.6%) | 21 |
| Pneumomediastinum | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pneumothorax | 11/161 (6.8%) | 13 | 11/160 (6.9%) | 13 |
| Pulmonary edema | 8/161 (5%) | 8 | 7/160 (4.4%) | 8 |
| Pulmonary edema aggravated | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pulmonary hemorrhage | 8/161 (5%) | 8 | 5/160 (3.1%) | 5 |
| Pulmonary hypertension | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Pulmonary pneumatocele | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Pulmonary vascular disorder | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Pulmonary venous congestion | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Respiratory acidosis | 4/161 (2.5%) | 4 | 0/160 (0%) | 0 |
| Respiratory alkalosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Respiratory distress | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Respiratory failure | 6/161 (3.7%) | 6 | 0/160 (0%) | 0 |
| Respiratory failure aggravated | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Respiratory insufficiency | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Sputum bloody | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Stridor | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Tachypnea | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Tension pneumothorax | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Upper airway obstruction | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Wheezing | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Bed sore | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Blister | 1/161 (0.6%) | 3 | 3/160 (1.9%) | 3 |
| Blistering | 2/161 (1.2%) | 2 | 1/160 (0.6%) | 1 |
| Blisters | 2/161 (1.2%) | 2 | 2/160 (1.3%) | 2 |
| Blood blister | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bullae | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bullous lesions | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Contact dermatitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Decubitus ulcer | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Dermatitis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ecchymosis | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Hives | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Livedo reticularis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Mottled skin | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Petechia | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Pressure sore | 3/161 (1.9%) | 3 | 2/160 (1.3%) | 3 |
| Pruritis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Rash | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Rash over arms | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Rash trunk | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Redness | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Scab | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Skin breakdown | 2/161 (1.2%) | 2 | 3/160 (1.9%) | 3 |
| Skin lesion | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Skin ulcer | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Subcutaneous emphysema | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Surgical and medical procedures | ||||
| Extracorporeal membrane oxygenation | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Extubation | 0/161 (0%) | 0 | 1/160 (0.6%) | 2 |
| Pulmonary artery banding | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Thoracic cavity drainage | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Vascular disorders | ||||
| Acute hypotension | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Aortic thrombosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Arterial thrombosis limb | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Axillary vein thrombosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Bleeding | 6/161 (3.7%) | 6 | 12/160 (7.5%) | 14 |
| Blood pressure high | 0/161 (0%) | 0 | 1/160 (0.6%) | 2 |
| Blood pressure labile | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Capillary leak syndrome | 1/161 (0.6%) | 1 | 3/160 (1.9%) | 3 |
| Clot blood | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Cold extremities | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| DVT of legs | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Deep vein thrombosis | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Deep vein thrombosis leg | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Deep venous thrombosis femoral | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Digital necrosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Embolism | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Embolus upper extremity | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Femoral artery occlusion | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Femoral artery thrombosis | 2/161 (1.2%) | 2 | 0/160 (0%) | 0 |
| Hematoma | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hemodynamic instability | 1/161 (0.6%) | 1 | 2/160 (1.3%) | 2 |
| Hypertension | 18/161 (11.2%) | 19 | 14/160 (8.8%) | 14 |
| Hypertensive crisis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Hypoperfusion | 0/161 (0%) | 0 | 3/160 (1.9%) | 3 |
| Hypotension | 26/161 (16.1%) | 32 | 24/160 (15%) | 26 |
| Hypotension aggravated | 4/161 (2.5%) | 4 | 4/160 (2.5%) | 4 |
| Hypotensive episode | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Inferior venacaval thrombosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ischemia | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Ischemia peripheral | 4/161 (2.5%) | 4 | 1/160 (0.6%) | 1 |
| Jugular vein distension | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Jugular vein thrombosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Leg ischemia | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Low BP | 0/161 (0%) | 0 | 2/160 (1.3%) | 2 |
| Low blood pressure | 1/161 (0.6%) | 1 | 1/160 (0.6%) | 1 |
| Peripheral embolism | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Peripheral vascular disorder | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Phlebitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Poor peripheral perfusion | 2/161 (1.2%) | 2 | 7/160 (4.4%) | 7 |
| Shock | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Subclavian vein thrombosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Superior vena cava syndrome | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Superior venacaval thrombosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Thrombophlebitis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Thrombosis | 0/161 (0%) | 0 | 1/160 (0.6%) | 1 |
| Thrombosis vena cava inferior | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Venous insufficiency | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
| Venous thrombosis | 1/161 (0.6%) | 1 | 0/160 (0%) | 0 |
Limitations/Caveats
[Not Specified]
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 | Dr. Rich Holubkov, Professor of Pediatrics |
|---|---|
| Organization | University of Utah |
| Phone | 807-587-3326 |
| richard.holubkov@hsc.utah.edu |
Responsible Party:
Frank W. Moler, M.D, M.S,
Professor of Pediatrics,
University of Michigan
ClinicalTrials.gov Identifier:
NCT00880087
Other Study ID Numbers:
- 620
- U01HL094345
First Posted:
Apr 13, 2009
Last Update Posted:
Jun 15, 2018
Last Verified:
May 1, 2018