California Transport Cooling Trial (CTCT)

December 1, 2014 updated by: Krisa P Van Meurs, Stanford University

A Randomized Clinical Trial of Therapeutic Hypothermia During Transport for Hypoxic Ischemic Encephalopathy (HIE): Device-regulated Cooling Versus Standard Practice.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University Children'S Hospital
      • Madera, California, United States, 93636
        • Children's Hospital Central California
      • Oakland, California, United States, 94609
        • Children's Hospital & Research Center
      • Oakland, California, United States, 94611
        • Kaiser Permanente Oakland/Walnut Creek
      • Palo Alto, California, United States, 94305
        • Stanford University
      • Sacramento, California, United States, 95819
        • Sutter Medical Center
      • San Diego, California, United States, 92123
        • Rady Childrens Hospital
      • San Francisco, California, United States, 94143
        • University of California San Francisco Medical Center
      • San Jose, California, United States, 95128
        • Santa Clara Valley Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 6 hours (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Control (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: Control (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 (servo-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: Device (servo-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.
Other Names:
  • Tecotherm Neo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Temperatures in Target Range During Transport
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
The percentage of temperatures in the target range (33°-34°C) during transport after cooling initiation by the transport team.
Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time to the target temperature range (33°-34°C) from initiation of cooling by the transport team
Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours
Percentage of Participants 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
Percentage of participants in target range (33°-34°C) one hour after cooling initiation by the transport team
Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours
Participants in Target Temperature Range Anytime During Transport
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
Participants in target temperature range (33-34 C) anytime during transport
Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The incidence, intervention and outcome of cardiac arrhythmia, major bleeding, altered skin integrity, pulmonary hypertension, device-related events, death, and other serious adverse events from the time of initiation of transport cooling to the time of completion will be monitored.
Participants will be followed for the duration of neonatal transport from the birth hospital to the cooling center, an expected average of 4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Inspiration Healthcare

Investigators

  • Principal Investigator: Krisa Van Meurs, M.D., Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (ACTUAL)

October 1, 2013

Study Completion (ACTUAL)

October 1, 2013

Study Registration Dates

First Submitted

September 6, 2012

First Submitted That Met QC Criteria

September 7, 2012

First Posted (ESTIMATE)

September 11, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

December 8, 2014

Last Update Submitted That Met QC Criteria

December 1, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22993

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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