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

NCT00147030 | Completed Results DMC

• 1 other identifier: ISRCTN89547571(1)
• Study Type: interventional
• Target: 325
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: Prolonged whole body cooling in term infants with perinatal asphyxial encephalopathy reduces death and severe neurodevelopmental disability. This study aims to determine whether whole body cooling to 33-34°C is a safe treatment that improves survival, without severe neurological or neurodevelopmental impairments at 18 months, of term infants suffering perinatal asphyxial encephalopathy.

Conditions

Asphyxia Neonatorum; Hypoxia; Encephalopathy; Seizures

Keywords

Hypoxia; Ischaemia; Encephalopathy; Neonatal; Hypothermia; Perinatal; Cooling; Whole/Total Body

Outcome Measures

Primary Outcomes (1)

• Combined Incidence of Mortality and Severe Neurodevelopmental Disability in Survivors

  Severe neurodevelopmental disability was defined as a score of less than 70 on the Mental Developmental Index of the Bayley Scales of Infant Development II (BSID-II) (on which the standardization mean \[± standard deviation (SD)\] is 100±15 and higher scores indicate better performance), a score of 3 to 5 on the Gross Motor Function Classification System (GMFCS) (on which scores can range from 1 to 5, with higher scores indicating greater impairment), or bilateral cortical visual impairment with no useful vision.

  18 months

Secondary Outcomes (21)

• Intracranial Haemorrhage

  Duration of hospital stay, on average 22 days

• Persistent Hypotension

  Duration of hospital stay, on average 22 days

• Pulmonary Haemorrhage

  Duration of hospital stay, on average 22 days

• Pulmonary Hypertension

  Duration of hospital stay, on average 22 days

• Prolonged Blood Coagulation Time

  Duration of hospital stay, on average 22 days

Study Arms (2)

cooled

ACTIVE COMPARATOR

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.

Procedure: Whole body mild induced hypothermia

non-cooled

NO INTERVENTION

Standard intensive care

Interventions

Whole body mild induced hypothermia PROCEDURE

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

cooled

Eligibility Criteria

• Age: 1 Hour - 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The infant will be assessed sequentially by criteria A, B and C listed below:
• A. Infants =\>36 completed weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) with at least one of the following:
• Apgar score of =\<5 at 10 minutes after birth
• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth
• Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary pH \<7.00)
• Base Deficit =\>16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth
• Infants that meet criteria A will be assessed for whether they meet the neurological abnormality entry criteria (B) by trained personnel:
• B. Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:
• hypotonia
• abnormal reflexes including oculomotor or pupillary abnormalities
• absent or weak suck
• clinical seizures
• Infants that meet criteria A \& B will be assessed by amplitude-integrated electroencephalogram (aEEG) (read by trained personnel):
• C. At least 30 minutes duration of amplitude integrated EEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following:
• normal background with some seizure activity

You may not qualify if:

• Infants expected to be \> 6 hours of age at the time of randomisation
• Major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator

Study Sites (1)

Hammersmith Hospital

London, W12 0NN, United Kingdom

Location

Related Publications (2)

• Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854.

  PMID: 19797281 RESULT

• Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol. 2010 Jan;9(1):39-45. doi: 10.1016/S1474-4422(09)70295-9. Epub 2009 Nov 5.

  PMID: 19896902 RESULT

MeSH Terms

Conditions

Asphyxia Neonatorum; Hypoxia; Brain Diseases; Seizures; Ischemia; Hypothermia

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Pathologic Processes; Body Temperature Changes

Results Point of Contact

• Title: Director of NPEU Clinical Trials Unit
• Organization: National Perinatal Epidemiology Unit, University of Oxford

ctu@npeu.ox.ac.uk

01865 289700

Study Officials

• Denis Azzopardi, MD; FRCPCH

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2005
• First Posted: September 7, 2005
• Study Start: December 1, 2002
• Primary Completion: November 1, 2006
• Study Completion: August 1, 2008
• Last Updated: May 11, 2016
• Results First Posted: May 11, 2016

Record last verified: 2013-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)