Trial from ANZCTR


Trial ID ACTRN12606000036516
Trial Status: Registered
Date Submitted: 2/05/2001
Date Registered: 2/05/2001
Retrospectively registered

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Public title A trial to determine if cooling newborn infants at risk of brain damage improves outcome
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Study title in 'Participant- Intervention- Comparator- Outcome (PICO)' format A randomised controlled trial of the effect of whole body cooling on the outcome of term infants with hypoxic ischaemic encephalopathy (ICE:Infant Cooling Evaluation trial)
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Secondary ID [1] 68 0
Perinatal Trials Registry: PTR367
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UTN
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Trial acronym ICE
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Health condition(s) or problem(s) studied:
Term infants with hypoxic ischaemic encephalopathy 61 0
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Condition category: Condition code:
Reproductive Health and Childbirth Complications of newborn
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Reproductive Health and Childbirth Children's - Brain
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72 72 0 0

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Descriptions of intervention(s) / exposure Cooling protocol
This group will have their core temperature lowered to 33.0oC-34.0oC. Temperature will be measured continuously by a thermistor inserted 5 cm into the rectum. Cooling will be started at the birth hospital after the infant has been assessed and stabilised. Cooling will be started and then continued for 72 hours. It will be achieved primarily by turning the radiant warmer off and exposing the infant to ambient temperature. Cool packs around 10oC may then be applied under the neck and across the chest as needed.
Active cooling will be reduced when the rectal temperature falls below 35 oC and stopped when below 34.5oC. The radiant warmer will be on with the skin temperature servo control set at 33.5oC. .
After 72 hours, re-warming will occur at a rate not exceeding 0.5OC every 2 hours.
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Intervention Code:
Prevention 859 0
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Comparator / control treatment The normal temperature group
This group will have their rectal temperature maintained between 36.7-37.3oC.
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Control group Active
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Primary Outcome: The primary outcome is survival free of major sensorineural disability at two years of age. 102 0
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Timepoint: Surviving infants will be assessed at two years of age by a paediatrician and psychologist blinded to treatment allocation. Major sensorineural disability will comprise cerebral palsy (not walking or unlikely to walk at 2 years), developmental delay (Mental Development Index score of the Bayley Scales of Infant Development <70), blindness (vision <6/60 in both eyes) and deafness requiring hearing aids, as described elsewhere (LD 19). 102 0
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Primary Outcome: The primary outcome is survival free of major sensorineural disability at two years of age.
Major sensorineural disability will comprise cerebral palsy (not walking or unlikely to walk at 2 years), developmental delay (Mental Development Index score of the Bayley Scales of Infant Development <70), blindness (vision <6/60 in both eyes) and deafness requiring hearing aids, as described elsewhere (LD 19).
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Timepoint: Surviving infants will be assessed at two years of age by a paediatrician and psychologist blinded to treatment allocation 1439 0
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Secondary Outcome: 2.Neurological status 208 0
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Timepoint: Assessed in the 72 hours after randomisation using the Sarnat classification (Finer modification) and on day 7 of life by the Optimality Score for Neurologic Examination Of Term Newborn. These are measurement tools that can be applied by any neonatologist. 208 0
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Secondary Outcome: 1.Acute effects during the 72 hours of cooling on: blood pressure, heart rate, haemoglobin, coagulation profile, white cell count, platelets, glucose, sodium, potassium, acid base status and lactate, urine output, respiratory status. 2544 0
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Secondary Outcome: 2.Neurological status: by the Optimality Score for Neurologic Examination Of Term Newborn. These are measurement tools that can be applied by any neonatologist. 2545 0
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Timepoint: Assessed in the 72 hours after randomisation using the Sarnat classification (Finer modification) and on day 7 of life. 2545 0
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Secondary Outcome: 3.Magnetic Resonance Imaging (MRI) will be done on all infants. A paediatric neuroradiologist blinded to treatment allocation will perform qualitative analysis of the cerebralcortex, basal ganglia and myelination in the posterior limb of the internal capsule. 2546 0
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Timepoint: On day 5-7. 2546 0
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Secondary Outcome: 4.Advanced MRI studies including MR spectrospcopy and diffusion MR techniques will also be performed simultaneously with (3) in a subset of infants in those centres that have the facilities. The result will be assessed for its usefulness in predicting adverse outcome and assisting clinical decisions. 2547 0
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Timepoint: 2547 0
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Key inclusion criteria 1) Infants of 35 weeks’ gestation or more, 2) Treatment at, or transport to, one of the participating study sites.3) Evidence of moderate or severe encephalopathy:4) Evidence of intrapartum hypoxia: at least two of: a)Apgar score of 5 or less at 10 minutes; b)Mechanical ventilation or resuscitation at 10 minutes; c)Cord pH < 7.00, or an arterial pH < 7.00 or base deficit of 12 or more within 60 minutes of birth
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Minimum age 35 Weeks
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Maximum age Not stated
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Gender Both males and females
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Healthy volunteers? No
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Key exclusion criteria 1) Cooling cannot be started within 6 hours of birth.2) Birth weight less than 2.0 kg3) Major congenital abnormalities including: a) Suspected neuromuscular disorders b) Chromosomal abnormalities c) Life threatening abnormalities of the cardiovascular or respiratory systems d) Suspected coagulopathye) Imperforate anus.4) Infants requiring an inspired oxygen over 80%.5) Infant in extremis i.e. very low blood pressure or severe acidosis unresponsive to treatment6) Active cooling has been initiated prior to randomisation
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Study type Interventional
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Purpose of the study Prevention
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Allocation to intervention Randomised controlled trial
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Describe the procedure for enrolling a subject and allocating the treatment (allocation concealment procedures) Sealed randomised envelopes are compiled by the CEBU department.
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Describe the methods used to generate the sequence in which subjects will be randomised (sequence generation) Computer generated AND stratified by particpating centre AND blocking
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Masking / blinding Open (masking not used)
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Who is / are masked / blinded (choose all that apply)


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Assignment Parallel
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Other design features
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Type of endpoint(s) Efficacy
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Statistical Methods/Analysis
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Phase Phase 3
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Anticipated date of first participant enrolment 8/11/2000
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Date of first participant enrolment
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Anticipated date last participant recruited/enrolled
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Actual date last participant recruited/enrolled
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Target sample size 300
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Recruitment status Recruiting
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Recruitment in Australia

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Recruitment outside Australia

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Funding Source: Government body 102 0
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Name: National Health & Medical Research Council 102 0
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Address: 102 0
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Country: Australia 102 0
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Funding Source: Government body 1176 0
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Name: NHMRC 1176 0
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Address: 1176 0
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Country: Australia 1176 0
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Primary Sponsor Other
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Name: Murdoch Children's Research Institute
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Country: Australia
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Secondary Sponsor: None 1036 0
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Name: N/A 1036 0
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Address: 1036 0
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Has the study received approval from at least one Ethics Committee? Yes
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Ethics Committee name: RoyalChildren’s Hosp 709 0
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Country: Australia 709 0
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HREC: 709 0
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Ethics Committee name: Royal Women’s Hosp 710 0
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Country: Australia 710 0
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Ethics Committee name: Mercy Hosp for Women 711 0
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Country: Australia 711 0
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Ethics Committee name: Princess Margaret & King Edward Memorial Hosp 712 0
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Ethics Committee name: Royal Hospital for Women 713 0
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Ethics Committee name: Royal Prince Alfred Hosp 714 0
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Ethics Committee name: Royal North Shore Hosp 715 0
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Ethics Committee name: Children’s Hosp. at Westmead 716 0
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Ethics Committee name: Liverpool Hosp 717 0
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Ethics Committee name: John Hunter Hosp 718 0
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Ethics Committee name: Westmead Hosp 719 0
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Country: Australia 719 0
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HREC: 719 0
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Ethics Committee name: Canberra Hosp 720 0
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Country: Australia 720 0
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HREC: 720 0
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Brief summary
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Trial website
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Principal Investigator
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Name: Dr Susan Jacobs
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Address: Royal Women's Hospital 132 Grattan St Carlton VIC 3053
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Country: Australia
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Tel: +61 3 93443144
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Email: sue.jacobs@rwh.org.au
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Name: Dr Susan Jacobs
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Address: Royal Women's Hospital 132 Grattan St Carlton VIC 3053
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