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TOBY (TOtal Body hYpothermia): a Study of Treatment for Perinatal Asphyxia

This study has been completed.
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT00147030
First received: September 5, 2005
Last updated: April 6, 2016
Last verified: November 2013
Results First Received: March 8, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Asphyxia Neonatorum
Hypoxia
Encephalopathy
Seizures
Intervention: Procedure: Whole body mild induced hypothermia

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Infants who met trial entry criteria were recruited at 40 Neonatal Intensive Care Units mainly in the United Kingdom and also in Europe. Recruitment took place over 4 years, from December 2006 to November 2006.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
494 infants were assessed for eligibility; 94 did not meet inclusion criteria, 30 declined to participate 45 were not enrolled for other reasons. 325 underwent randomization.

Reporting Groups
  Description
Cooled

Whole body mild induced hypothermia for 72 hours, starting by 6 hours of age, in addition to standard intensive care. After 72 hours of cooling, rewarming by a maximum of 0.5 degree C / hour to normothermia.

Whole body mild induced hypothermia: Target rectal temperature 33-34°C for 72 hours, commencing by 6 hours of age; followed by re-warming at 0.5°C to normothermia

Non-cooled Standard intensive care at normothermia

Participant Flow:   Overall Study
    Cooled     Non-cooled  
STARTED     163     162  
COMPLETED     163     162  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Infants who were less than 6 hours of age who had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy confirmed by 30 minutes’ amplitude-integrated electro-encephalography that showed abnormal background activity or seizures.

Reporting Groups
  Description
Cooled Whole body mild induced hypothermia 72 hours, commencing by 6 hours of age followed by re-warming to normothermia.
Non-cooled Standard intensive care
Total Total of all reporting groups

Baseline Measures
    Cooled     Non-cooled     Total  
Number of Participants  
[units: participants]
  163     162     325  
Age, Customized [1]
[units: participants]
     
Age 0-4 hours     48     57     105  
Age 4-6 hours     115     105     220  
Gender  
[units: participants]
     
Female     62     74     136  
Male     101     88     189  
[1] All participants were < 6 hours of age at randomization.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Combined Incidence of Mortality and Severe Neurodevelopmental Disability in Survivors   [ Time Frame: 18 months ]

2.  Secondary:   Intracranial Haemorrhage   [ Time Frame: Duration of hospital stay, on average 22 days ]

3.  Secondary:   Persistent Hypotension   [ Time Frame: Duration of hospital stay, on average 22 days ]

4.  Secondary:   Pulmonary Haemorrhage   [ Time Frame: Duration of hospital stay, on average 22 days ]

5.  Secondary:   Pulmonary Hypertension   [ Time Frame: Duration of hospital stay, on average 22 days ]

6.  Secondary:   Prolonged Blood Coagulation Time   [ Time Frame: Duration of hospital stay, on average 22 days ]

7.  Secondary:   Culture Proven Sepsis   [ Time Frame: Duration of hospital stay, on average 22 days ]

8.  Secondary:   Necrotising Enterocolitis   [ Time Frame: Duration of hospital stay, on average 22 days ]

9.  Secondary:   Cardiac Arrhythmia   [ Time Frame: Duration of hospital stay, on average 22 days ]

10.  Secondary:   Thrombocytopenia   [ Time Frame: Duration of hospital stay, on average 22 days ]

11.  Secondary:   Major Venous Thrombosis   [ Time Frame: Duration of hospital stay, on average 22 days ]

12.  Secondary:   Renal Failure Treated With Dialysis   [ Time Frame: Duration of hospital stay, on average 22 days ]

13.  Secondary:   Pneumonia   [ Time Frame: Before discharge from hospital ]

14.  Secondary:   Pulmonary Airleak   [ Time Frame: Duration of hospital stay, on average 22 days ]

15.  Secondary:   Duration of Hospitalisation   [ Time Frame: Duration of hospital stay, on average 22 days ]

16.  Secondary:   Mortality   [ Time Frame: 18 months ]

17.  Secondary:   Severe Neurodevelopmental Disability   [ Time Frame: 18 months ]

18.  Secondary:   Multiple Handicap   [ Time Frame: 18 months ]

19.  Secondary:   Bayley Psychomotor Developmental Index Score (PDI)   [ Time Frame: 18 months ]

20.  Secondary:   Sensorineural Hearing Loss   [ Time Frame: 18 months ]

21.  Secondary:   Epilepsy (Defined as Recurrent Seizures Beyond the Neonatal Period, Requiring Anticonvulsant Therapy at the Time of Assessment)   [ Time Frame: 18 months ]

22.  Secondary:   Microcephaly   [ Time Frame: 18 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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: Director of NPEU Clinical Trials Unit
Organization: National Perinatal Epidemiology Unit, University of Oxford
phone: 01865 289700 ext 89728
e-mail: ctu@npeu.ox.ac.uk


Publications of Results:

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00147030     History of Changes
Other Study ID Numbers: ISRCTN89547571(1)
Study First Received: September 5, 2005
Results First Received: March 8, 2016
Last Updated: April 6, 2016
Health Authority: United Kingdom: Research Ethics Committee