Trial registered on ANZCTR


Trial ID
ACTRN12606000036516
Ethics application status
Approved
Date submitted
2/05/2001
Date registered
2/05/2001
Type of registration
Retrospectively registered

Titles & IDs
Public title
A trial to determine if cooling newborn infants at risk of brain damage improves outcome
Scientific title
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)
Secondary ID [1] 68 0
Perinatal Trials Registry: PTR367
Universal Trial Number (UTN)
Trial acronym
ICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Term infants with hypoxic ischaemic encephalopathy 61 0
Condition category
Condition code
Reproductive Health and Childbirth 71 71 0 0
Complications of newborn
Reproductive Health and Childbirth 72 72 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description 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.
Intervention code [1] 859 0
Prevention
Comparator / control treatment
The normal temperature group
This group will have their rectal temperature maintained between 36.7-37.3oC.
Control group
Active

Outcomes
Primary outcome [1] 102 0
The primary outcome is survival free of major sensorineural disability at two years of age.
Timepoint [1] 102 0
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).
Primary outcome [2] 1439 0
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).
Timepoint [2] 1439 0
Surviving infants will be assessed at two years of age by a paediatrician and psychologist blinded to treatment allocation
Secondary outcome [1] 208 0
2.Neurological status
Timepoint [1] 208 0
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.
Secondary outcome [2] 2544 0
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.
Timepoint [2] 2544 0
Secondary outcome [3] 2545 0
2.Neurological status: by the Optimality Score for Neurologic Examination Of Term Newborn. These are measurement tools that can be applied by any neonatologist.
Timepoint [3] 2545 0
Assessed in the 72 hours after randomisation using the Sarnat classification (Finer modification) and on day 7 of life.
Secondary outcome [4] 2546 0
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.
Timepoint [4] 2546 0
On day 5-7.
Secondary outcome [5] 2547 0
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.
Timepoint [5] 2547 0

Eligibility
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
Minimum age
35 Weeks
Maximum age
Not stated
Gender
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed randomised envelopes are compiled by the CEBU department.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated AND stratified by particpating centre AND blocking
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy

Recruitment
Anticipated date of first participant enrolment
8/11/2000
Actual date of first participant enrolment
Anticipated date last participant enrolled
Actual date last participant enrolled
Anticipated date of last data collection
Actual date of last data collection
Target sample size
300
Actual sample size
Recruitment status
Recruiting
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 102 0
Government body
Name [1] 102 0
National Health & Medical Research Council
Address [1] 102 0
Country [1] 102 0
Australia
Funding source category [2] 1176 0
Government body
Name [2] 1176 0
NHMRC
Address [2] 1176 0
Country [2] 1176 0
Australia
Primary sponsor type
Other
Name
Murdoch Children's Research Institute
Address
Country
Australia
Secondary sponsor category [1] 1036 0
None
Name [1] 1036 0
N/A
Address [1] 1036 0
Country [1] 1036 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 709 0
RoyalChildren’s Hosp
Ethics committee address [1] 709 0
Ethics committee country [1] 709 0
Australia
Date submitted for ethics approval [1] 709 0
Approval date [1] 709 0
Ethics approval number [1] 709 0
Ethics committee name [2] 710 0
Royal Women’s Hosp
Ethics committee address [2] 710 0
Ethics committee country [2] 710 0
Australia
Date submitted for ethics approval [2] 710 0
Approval date [2] 710 0
Ethics approval number [2] 710 0
Ethics committee name [3] 711 0
Mercy Hosp for Women
Ethics committee address [3] 711 0
Ethics committee country [3] 711 0
Australia
Date submitted for ethics approval [3] 711 0
Approval date [3] 711 0
Ethics approval number [3] 711 0
Ethics committee name [4] 712 0
Princess Margaret & King Edward Memorial Hosp
Ethics committee address [4] 712 0
Ethics committee country [4] 712 0
Australia
Date submitted for ethics approval [4] 712 0
Approval date [4] 712 0
Ethics approval number [4] 712 0
Ethics committee name [5] 713 0
Royal Hospital for Women
Ethics committee address [5] 713 0
Ethics committee country [5] 713 0
Australia
Date submitted for ethics approval [5] 713 0
Approval date [5] 713 0
Ethics approval number [5] 713 0
Ethics committee name [6] 714 0
Royal Prince Alfred Hosp
Ethics committee address [6] 714 0
Ethics committee country [6] 714 0
Australia
Date submitted for ethics approval [6] 714 0
Approval date [6] 714 0
Ethics approval number [6] 714 0
Ethics committee name [7] 715 0
Royal North Shore Hosp
Ethics committee address [7] 715 0
Ethics committee country [7] 715 0
Australia
Date submitted for ethics approval [7] 715 0
Approval date [7] 715 0
Ethics approval number [7] 715 0
Ethics committee name [8] 716 0
Children’s Hosp. at Westmead
Ethics committee address [8] 716 0
Ethics committee country [8] 716 0
Australia
Date submitted for ethics approval [8] 716 0
Approval date [8] 716 0
Ethics approval number [8] 716 0
Ethics committee name [9] 717 0
Liverpool Hosp
Ethics committee address [9] 717 0
Ethics committee country [9] 717 0
Australia
Date submitted for ethics approval [9] 717 0
Approval date [9] 717 0
Ethics approval number [9] 717 0
Ethics committee name [10] 718 0
John Hunter Hosp
Ethics committee address [10] 718 0
Ethics committee country [10] 718 0
Australia
Date submitted for ethics approval [10] 718 0
Approval date [10] 718 0
Ethics approval number [10] 718 0
Ethics committee name [11] 719 0
Westmead Hosp
Ethics committee address [11] 719 0
Ethics committee country [11] 719 0
Australia
Date submitted for ethics approval [11] 719 0
Approval date [11] 719 0
Ethics approval number [11] 719 0
Ethics committee name [12] 720 0
Canberra Hosp
Ethics committee address [12] 720 0
Ethics committee country [12] 720 0
Australia
Date submitted for ethics approval [12] 720 0
Approval date [12] 720 0
Ethics approval number [12] 720 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36370 0
Address 36370 0
Country 36370 0
Phone 36370 0
Fax 36370 0
Email 36370 0
Contact person for public queries
Name 10048 0
Dr Susan Jacobs
Address 10048 0
Royal Women's Hospital
132 Grattan St
Carlton VIC 3053
Country 10048 0
Australia
Phone 10048 0
+61 3 93443144
Fax 10048 0
+61 3 93442185
Email 10048 0
sue.jacobs@rwh.org.au
Contact person for scientific queries
Name 976 0
Dr Susan Jacobs
Address 976 0
Royal Women's Hospital
132 Grattan St
Carlton VIC 3053
Country 976 0
Australia
Phone 976 0
+61 3 93443144
Fax 976 0
+61 3 93442185
Email 976 0
sue.jacobs@rwh.org.au