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TOBY: a Study of Treatment for Perinatal Asphyxia

This study is ongoing, but not recruiting participants.

Sponsors and Collaborators: Imperial College London
Medical Research Council
Information provided by: Imperial College London
ClinicalTrials.gov Identifier: NCT00147030
  Purpose

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.


Condition Intervention
Asphyxia Neonatorum
Hypoxia
Encephalopathy
Seizures
Procedure: Whole body mild induced hypothermia

MedlinePlus related topics:   Hypothermia    Seizures   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:   Whole Body Hypothermia for the Treatment of Perinatal Asphyxial Encephalopathy

Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Combined incidence of mortality and severe neurodevelopmental disability in survivors [ Time Frame: 18 months ]

Secondary Outcome Measures:
  • Intracranial haemorrhage [ Time Frame: Before discharge from hospital ]
  • Persistent hypotension [ Time Frame: Before discharge from hospital ]
  • Pulmonary haemorrhage [ Time Frame: Before discharge from hospital ]
  • Pulmonary hypertension [ Time Frame: Before discharge from hospital ]
  • Prolonged blood coagulation time [ Time Frame: Before discharge from hospital ]
  • Culture proven sepsis [ Time Frame: Before discharge from hospital ]
  • Necrotising enterocolitis [ Time Frame: Before discharge from hospital ]
  • Cardiac arrhythmia [ Time Frame: Before discharge from hospital ]
  • Thrombocytopenia [ Time Frame: Before discharge from hospital ]
  • Major venous thrombosis [ Time Frame: Before discharge from hospital ]
  • Renal failure treated with dialysis [ Time Frame: Before discharge from hospital ]
  • Pneumonia [ Time Frame: Before discharge from hospital ]
  • Pulmonary airleak [ Time Frame: Before discharge from hospital ]
  • Duration of hospitalisation [ Time Frame: Before discharge from hospital ]
  • Mortality [ Time Frame: 18 months ]
  • Severe neurodevelopmental disability [ Time Frame: 18 months ]
  • Multiple handicap (defined as the presence of any two of the following in an infant; neuromotor disability (Level 3-5 on GMF classification), mental delay (Bayley MDI score < 70), epilepsy, cortical visual impairment, sensorineural hearing loss) [ Time Frame: 18 months ]
  • Bayley PDI score [ Time Frame: 18 months ]
  • Sensorineural hearing loss: 40 dB [ Time Frame: 18 months ]
  • Epilepsy (defined as recurrent seizures beyond the neonatal period, requiring anticonvulsant therapy at the time of assessment) [ Time Frame: 18 months ]
  • Microcephaly (head circumference more than 2 standard deviations below the mean). [ Time Frame: 18 months ]

Enrollment:   325
Study Start Date:   December 2002
Estimated Study Completion Date:   August 2008

Arms Assigned Interventions
1: Active Comparator Procedure: 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
2: No Intervention

Detailed Description:

This is a multicentre prospective randomised controlled trial to determine whether a reduction of body temperature by 3-4°C following perinatal asphyxia improves survival without neurodevelopmental disability.

Full term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 ± 0.2°C or to whole body cooling with the rectal temperature kept at 33.5 ± 0.5°C for 72 hours followed by slow rewarming.

The outcome will be assessed at 18 months of age by survival and neurological and neurodevelopmental testing.

Eligibility criteria:

Term infants less than 6 hours after birth with moderate or severe perinatal asphyxia (a combination of clinical and EEG criteria).

Exclusion criteria:

Infants expected to be 6 hours of age at the time of randomisation or infants with major congenital abnormalities.

Intervention:

Intensive care with whole body cooling versus intensive care without whole body cooling (babies are cooled to 33.5°C for 72 hours)

Main Outcomes:

Death and severe neurodevelopmental impairment at 18 months of age

Secondary Outcomes:

Cerebral thrombosis or haemorrhage, persistent hypotension, pulmonary hypertension, abnormal coagulation, arrhythmia and sepsis in the neonatal period. Neurological impairments at 18 months

Number of patients required: 236.

On 30th November 2006, when recruitment closed, 325 babies had been recruited.

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

Criteria

Inclusion criteria

The infant will be assessed sequentially by criteria A, B and C listed below:

A. Infants =>36 completed weeks gestation admitted to the 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 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
  • moderately abnormal activity
  • suppressed activity
  • continuous seizure activity

Exclusion criteria

  • 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
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00147030

Locations
United Kingdom
Hammersmith Hospital    
      London, United Kingdom, W12 0NN

Sponsors and Collaborators
Imperial College London
Medical Research Council

Investigators
Principal Investigator:     Denis Azzopardi, MD; FRCPCH     Imperial College London    
  More Information


The TOBY study website  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   ISRCTN89547571
First Received:   September 5, 2005
Last Updated:   October 24, 2007
ClinicalTrials.gov Identifier:   NCT00147030
Health Authority:   United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Hypoxia  
Ischaemia  
Encephalopathy  
Neonatal  
Hypothermia
Perinatal
Cooling
Whole/Total Body

Study placed in the following topic categories:
Asphyxia Neonatorum
Hypothermia
Death
Seizures
Wounds and Injuries
Disorders of Environmental Origin
Ischemia
Anoxia
Signs and Symptoms
Infant, Newborn, Diseases
Signs and Symptoms, Respiratory
Asphyxia neonatorum
Asphyxia

Additional relevant MeSH terms:
Pathologic Processes

ClinicalTrials.gov processed this record on October 06, 2008




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