California Transport Cooling Trial (CTCT)

This study has been completed.
Sponsor:
Collaborator:
Inspiration Healthcare LTD UK
Information provided by (Responsible Party):
Krisa P Van Meurs, Stanford University
ClinicalTrials.gov Identifier:
NCT01683383
First received: September 6, 2012
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

Hypoxic ischemic encephalopathy (HIE) remains a major cause of death and severe disability despite advances in neonatal and perinatal medicine. Therapeutic hypothermia is the single most promising intervention for HIE. Reduction of brain temperature by 2° to 5°C has shown to be neuroprotective in newborn and adult animal models of brain ischemia. Therapeutic hypothermia instituted within 6 hours of birth has been shown to significantly improve survival and neurodevelopmental outcome in term newborns with HIE. Hypothermia is most effective if begun during the latent period, before the secondary energy failure. It is not known whether cooling initiated after 6 hours of age is effective.

The goal of this proposal is to test the efficacy of the cooling device in achieving the target temperatures in patients with moderate to severe HIE during transport when compared with current practices.


Condition Intervention
Hypoxic Ischemic Encephalopathy
Device: Servo-regulated cooling device, Tecotherm Neo
Other: Standard Practice

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial of Therapeutic Hypothermia During Transport for Hypoxic Ischemic Encephalopathy (HIE): Device-regulated Cooling Versus Standard Practice.

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Percentage of temperatures in target range [ Time Frame: Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours ] [ Designated as safety issue: No ]
    The percentage of temperatures in the target range (33°-34°C) both within and between enrolled infants after cooling initiation by the transport team.


Secondary Outcome Measures:
  • Time to target temperature [ Time Frame: Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours ] [ Designated as safety issue: No ]
    Time to the target temperature range (33°-34°C) from initiation of cooling by the transport team

  • Percentage of infants in the target range at 1 hour [ Time Frame: Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours ] [ Designated as safety issue: No ]
    Percentage of infants in target range (33°-34°C) one hour after cooling initiation by the transport team

  • Temperature ranges [ Time Frame: Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours ] [ Designated as safety issue: No ]
    Range of temperatures during transport


Other Outcome Measures:
  • Safety outcomes [ Time Frame: Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours ] [ Designated as safety issue: Yes ]
    The incidence, intervention and outcome of cardiac arrhythmia, major bleeding, altered skin integrity, pulmonary hypertension, death and other serious adverse events from the time of initiation of transport cooling to the time of completion will be monitored


Enrollment: 100
Study Start Date: September 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Practice
Subjects in Arm 1 will receive passive or active cooling as per center practice with rectal temperatures being recorded every 15 minutes.
Other: Standard Practice
Subjects in Arm 1 will receive passive or active cooling as per center practice with rectal temperatures being recorded every 15 minutes.
Experimental: Device regulated cooling
Subjects in Arm 2 will be placed on cooling blanket connected to the Tecotherm Neo (Inspiration Healthcare LTD UK). Temperature will be monitored continuously and servo-regulated using a rectal temperature probe.
Device: Servo-regulated cooling device, Tecotherm Neo
Subjects in Arm 2 will be placed on a cooling blanket connected to the Tecotherm Neo. Temperatures will be monitored continuously and servo-regulated using a rectal temperature probe.

  Hide Detailed Description

Detailed Description:

Statement of the Problem:

Hypoxic ischemic encephalopathy (HIE) remains a major cause of death and severe disability despite advances in neonatal and perinatal medicine. Therapeutic hypothermia is the single most promising intervention for HIE. Reduction of brain temperature by 2° to 5°C has shown to be neuroprotective in newborn and adult animal models of brain ischemia. Therapeutic hypothermia instituted within 6 hours of birth has been shown to significantly improve survival and neurodevelopmental outcome in term newborns with HIE. Hypothermia is most effective if begun during the latent period, before secondary energy failure. It is not known whether cooling initiated after 6 hours of age is effective. Animal studies have shown that the sooner the initiation of cooling, the better the outcome. They have also suggested that the latent period may be shorter with a more severe insult. Cooling should be initiated as soon as possible, preferably within 2 hours and not later than 6 hours. There have been six large randomized clinical trials supporting the efficacy of therapeutic hypothermia for HIE and it is now the standard of care in the U.S. and internationally.

Once a patient qualifies for cooling, whole body cooling or selective head cooling is initiated. However, most birth hospitals do not have the ability to provide therapeutic hypothermia; thus, patients must be transported to Level 3 NICUs specially equipped to provide this therapy. As there is a limited therapeutic window for induction of hypothermia, it would be ideal to initiate therapeutic hypothermia as soon as the patient qualifies for cooling therapy. If cooling is initiated at the birth hospital, neuroprotective temperatures can be achieved several hours prior to arrival in the cooling center.

At this time patients cooled in transport receive passive cooling (turning off the active warming devices such as the transport isolette) or active cooling (ice packs placed around the baby). These practices have been shown to present a significant risk for over-cooling and under-cooling. The risks associated with excessive cooling include bradycardia, cardiac arrest, and coagulation disturbances. Undercooling likely results in reduced efficacy of the neuroprotective effects provided by therapeutic hypothermia.

Primary and secondary endpoints Primary end point: The percentage of temperatures in the target range (33°-34°C) both within and between enrolled infants after cooling initiation by the transport team.

Secondary end point: Time to the target temperature range (33°-34°C), percentage of newborns in target temperature range one hour after cooling initiation by transport team, and temperature ranges.

Study Design The proposed California Transport Cooling Trial (CTCT) is a prospective randomized multi-center clinical trial to be conducted by nine transport teams based at level III NICUs in California who perform therapeutic hypothermia for HIE. The on-call neonatologist at the participating cooling center will determine if the infant qualifies for cooling. Infants greater than or equal to 35 weeks and less than six hours of age who are being transported to a cooling center will be eligible. The transport team will randomize the infant to either cooling as per center practice (Arm 1) or device-regulated cooling (Arm 2). Subjects in Arm 1 will receive passive or active cooling as per center practice with rectal temperatures being recorded every 15 minutes. Subjects in Arm 2 will be placed on cooling blanket connected to the Tecotherm Neo. Temperature will be monitored continuously and servo-regulated using a rectal temperature probe. Pertinent clinical data will be collected using CPQCC/CPeTS data forms and CTCT data forms. Temperatures from initiation of cooling until admission to the cooling center will be analyzed for percentage of temperatures in the target range after cooling initiation by the transport team, time to target temperature range, percentage of newborns in the target temperature range 1 hour after cooling initiation by the transport team, and temperature ranges. ANOVA method will be used to compare the temperature ranges across arms. Cox proportional hazard model will be used to compare time to target temperature. Safety outcomes will be compared using standard logistic regression.

Study Methods Subjects assigned to Arm 1 will be cooled as per the usual center practice with recording of rectal temperatures every 15 minutes. Arm 2 subjects will be cooled using a portable servo-regulated cooling device using a rectal probe. Temperatures will be stored on the memory card every minute. No PHI will be stored in the cooling device. Data will be downloaded from the device at the conclusion of the transport.

Sample Size and Estimated Study Duration Power calculations for this study were based on anticipated 140 patients requiring initiation of therapeutic hypothermia by nine transport teams over a period of one year. A 70% consent rate and 50 patients per arm will provide 90% power to detect 30% absolute difference in the percentage of temperatures in the target range assuming a standard deviation for percentage of temperature in the target range of 45% based on the Kendall study, published in Archives of Diseases of Childhood in 2010. All analyses will adjust for center and will be two-sided and conducted at the 0.05 level of significance.

We estimate that patient enrollment will take approximately one year. Data analysis, manuscript preparation, and submission will be completed within 6 months of completion of enrollment.

  Eligibility

Ages Eligible for Study:   up to 6 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Term or near-term infants with gestational age ≥35 weeks who meet institutional criteria for use of therapeutic hypothermia and in whom the decision has been made to perform cooling during transport.

Exclusion Criteria:

  • Presence of a congenital or lethal chromosomal anomaly
  • Decision to not provide full intensive care
  • Refusal to consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01683383

Locations
United States, California
Loma Linda University Children's Hospital
Loma Linda, California, United States, 92354
Children's Hospital Central California
Madera, California, United States, 93636
Kaiser Permanente Oakland/Walnut Creek
Oakland, California, United States, 94611
Children's Hospital & Research Center
Oakland, California, United States, 94609
Stanford University
Palo Alto, California, United States, 94305
Sutter Medical Center
Sacramento, California, United States, 95819
Rady Childrens Hospital
San Diego, California, United States, 92123
University of California San Francisco Medical Center
San Francisco, California, United States, 94143
Santa Clara Valley Medical Center
San Jose, California, United States, 95128
Sponsors and Collaborators
Stanford University
Inspiration Healthcare LTD UK
Investigators
Principal Investigator: Krisa Van Meurs, M.D. Stanford University
  More Information

Publications:

Responsible Party: Krisa P Van Meurs, Professor of Pediatrics, Stanford University
ClinicalTrials.gov Identifier: NCT01683383     History of Changes
Other Study ID Numbers: 22993
Study First Received: September 6, 2012
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Stanford University:
Hypoxic ischemic encephalopathy
Therapeutic hypothermia
Whole body cooling
Transport cooling

Additional relevant MeSH terms:
Brain Ischemia
Ischemia
Brain Diseases
Hypoxia-Ischemia, Brain
Cerebrovascular Disorders
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Hypoxia, Brain

ClinicalTrials.gov processed this record on August 19, 2014