Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery

• Sponsor: Alexa Craig (Other)
• Overall Status: Completed
• CT.gov ID: NCT03036072
• Collaborator: MaineHealth (Other)
• Enrollment: 25
• Location: 1
• Arms: 2
• Actual Duration (Months): 36
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is an unblinded, single center, randomized study of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, randomized to either the delayed rewarming intervention or to the standard of care (strict normothermia).

Condition or Disease	Intervention/Treatment	Phase
Post-Op Complication	Other: Strict normothermia; Device: Delayed Rewarming	N/A

Detailed Description

Control Group:

The congenital heart surgery will be performed according to usual practice with the degree of intra-operative hypothermia determined by the cardiothoracic surgeon based on the anticipated complexity of the case. Following completion of the surgical procedure, the infant will be rapidly rewarmed on CPB at a rate of 0.2 to 0.3°C per minute to a normothermic temperature of 36.5°C. Infants in this group will be given a single weight-based 15 mg/kg dose of intravenous Tylenol in the operating room (OR) by the anesthesiologist as the chest is being closed. The infant will be transported to the Pediatric Intensive Care Unit (PICU) for routine post-operative monitoring. If the infant develops a fever, ice packs will be applied to the axilla and groin per usual routine and removed once the fever has abated.

Experimental group:

Partial rewarming will occur on CPB to 35°C. During the last hour of surgery, the infant's temperature will be maintained at 35°C while the chest is closed by using a BairHugger and lowering the room temperature. Transfusions of packed red blood cells, fresh frozen plasma and cryoprecipitate will not be automatically warmed. Infants will be given a single 15 mg/kg dose of IV Tylenol in the OR. The infant will be transported to the PICU at 35°C and placed on the temperature-regulating blanket. The infant will be incrementally rewarmed with increases in temperature of 0.3°C every 2 hours for 6 hours, then 0.2°C every 2 hours for 6 hours to the goal temperature of 36.5°C. Once the infant is stable, EEG will be performed for 48 hours to screen for seizures. The PI will interpret the EEG every 6-8 hours. The infant will remain on the blanket at 36.5°C for another 12 hours. The blanket and esophageal temperature probe will then be removed a total of 24 hours after surgery was completed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Strict Normothermia Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.	Other: Strict normothermia
Experimental: Delayed Rewarming Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.	Device: Delayed Rewarming; Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.

Outcome Measures

Primary Outcome Measures

1. Infants With Elevated s100b and NSE [4 days]

   In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?

Secondary Outcome Measures

1. Number of Participants With Adverse Events [4 days]

   In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 6 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of congenital heart disease requiring congenital heart surgery on bypass

2. Age less than 6 months at the time of surgery

3. Intra-operative hypothermia less than or equal to 35°C

Exclusion Criteria:

1. Concern for underlying coagulation disorder such as hemophilia

2. Death in the operating room

3. Inability to wean of cardiopulmonary bypass at conclusion of surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maine Medical Center	Portland	Maine	United States	04102

Sponsors and Collaborators

• Alexa Craig
• MaineHealth

Investigators

• Principal Investigator: Alexa K Craig, MD, MSc, Assistant Professor of Pediatrics

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 31, 2017

More Information

Publications

None provided.

• Responsible Party: Alexa Craig, Assistant Professor of Pediatrics, MaineHealth
• ClinicalTrials.gov Identifier: NCT03036072
• Other Study ID Numbers: IRB 4489; 4KL2TR001063-04
• First Posted: Jan 30, 2017
• Last Update Posted: Jul 13, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Alexa Craig, Assistant Professor of Pediatrics, MaineHealth: Therapeutic Hypothermia
• Additional relevant MeSH terms: Postoperative Complications

Study Results

Participant Flow

Arm/Group Title	Strict Normothermia	Delayed Rewarming
Arm/Group Description	Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU. Strict normothermia	Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours. Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.
Period Title: Overall Study
STARTED	12	13
COMPLETED	12	10
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Strict Normothermia	Delayed Rewarming	Total
Arm/Group Description	Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU. Strict normothermia	Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours. Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.	Total of all reporting groups
Overall Participants	12	10	22
Age, Customized (Count of Participants)
Less than 2 weeks at surgery	4 33.3%	3 30%	7 31.8%
More than 2 weeks at surgery	8 66.7%	7 70%	15 68.2%
Sex: Female, Male (Count of Participants)
Female	4 33.3%	4 40%	8 36.4%
Male	8 66.7%	6 60%	14 63.6%
Race/Ethnicity, Customized (Count of Participants)
White	10 83.3%	8 80%	18 81.8%
Unknown	2 16.7%	2 20%	4 18.2%
Region of Enrollment (participants) [Number]
United States	12 100%	10 100%	22 100%
Trisomy 21 (Count of Participants)
Count of Participants [Participants]	4 33.3%	2 20%	6 27.3%

Outcome Measures

1. Primary Outcome

Title	Infants With Elevated s100b and NSE
Description	In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Laboratory storage and transportation issues resulted in less than expected number of viable specimens that could be analyzed at all 5 time points.

Arm/Group Title	Strict Normothermia	Delayed Rewarming
Arm/Group Description	Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU. Strict normothermia	Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours. Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.
Measure Participants	12	10
Count of Participants [Participants]	11 91.7%	9 90%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Strict Normothermia	Delayed Rewarming
Arm/Group Description	Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU. Strict normothermia	Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours. Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.
Measure Participants	12	10
Count of Participants [Participants]	3 25%	3 30%

Adverse Events

Time Frame	Until 48 hours post surgery.
Arm/Group Title	Strict Normothermia		Delayed Rewarming
Arm/Group Description	Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU. Strict normothermia		Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours. Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.
All Cause Mortality
	Strict Normothermia		Delayed Rewarming
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/10 (10%)
Serious Adverse Events
	Strict Normothermia		Delayed Rewarming
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		2/10 (20%)
Cardiac disorders
ECMO after surgery	1/12 (8.3%)	1	1/10 (10%)	1
CPR after surgery	1/12 (8.3%)	1	0/10 (0%)	0
Return to Operating Room	3/12 (25%)	3	1/10 (10%)	1
Nervous system disorders
Stroke or Seizure	0/12 (0%)	0	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Strict Normothermia		Delayed Rewarming
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.