International Neonatal Immunotherapy Study

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International Neonatal Immunotherapy Study

• National Perinatal Epidemiology Unit
• Oxford
• www.npeu.ox.ac.uk

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Co-ordinating centre

• INIS is run by the National Perinatal
  Epidemiology Unit, Oxford
• Please visit our site at www.npeu.ox.ac.uk
• If you have any queries please contact
• Barbara Farrell (Trial Director)
• Clare Shakeshaft (Study Co-ordinator)

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INIS current status

• Start of trial 2001
• Participating centres 97
• Participating countries 9
• Babies recruited 3,292 (March 07)
• See www.npeu.ac.uk/inis for current update

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INIS Co-ordinating Team

• Peter Brocklehurst Chief Investigator
• Barbara Farrell Trial Director
• Clare Shakeshaft Study Co-ordinator
• Caroline Wilson Follow up Co-ordinator
• Andy King Programmer
• Rui Zhao Data Assistant
• Ellie Morgan-Jones Administrative Assistant

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INIS - future

• Aim
• To reach a target of at least 3500 babies by end
  of recruitment 31st May 2007

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INIS hypothesis

• That, in infants receiving antibiotics for
  clinical sepsis, the addition of non-specific
  immunoglobulin (IVIG) reduces mortality and major
  morbidity compared with antibiotics alone

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INIS - study design

• Gold standard for treatment trials
• Double-blind
• Randomised
• Placebo -controlled

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Receiving antibiotics and proven or suspected
serious infection
IVIG
Placebo
Mortality or major disability
at 2 years
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Eligibility criteria

• 1.Receiving antibiotics and suspected or proven
  serious infection
• AND

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Eligibility criteria

• 2. At least one of the following
• birth weight less than 1500g
• receiving respiratory support via an endotracheal
  tube
• evidence of infection in blood culture, CSF or
  usually sterile body fluid
• AND

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Eligibility criteria

• AND
• 3. There is substantial uncertainty that IVIG is
  indicated

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Exclusion criteria

• IVIG already given
• IVIG thought to be needed or contraindicated
• specific IVIG

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Specific IVIG

• IVIG for specific indications should be given as
  per hospital policy and these infants will still
  be eligible
• Hepatitis B immunoglobulin
• Varicella-Zoster immunoglobulin

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Eligibility - age

• Babies at any age whilst resident on NICU
• After discharge babies are eligible until EDD
  plus 28 days

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Consent

• Consent must be fully informed and obtained
  before randomisation
• Use the Information Leaflet
• Direct parents to website or INIS contact

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Randomisation

• Simple, no phone call required
• Drug boxes in pre-randomised sequence
• Use lowest numbered box

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IVIG

• Plasma from non-UK donors
• Produced by Scottish National Blood Transfusion
  Service
• Tested for HIV 1 ,2 and Hepatitis A,B,C
• Excellent safety record
• Few adverse reactions

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Placebo

• 0.2 albumin
• Identical appearance to IVIG
• Safety record as for IVIG

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Follow-up

• Parent questionnaire
• Paediatrician questionnaire
• Completed at 2 year corrected age

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Primary outcomes

• Death or
• Major disability at 2 years corrected age

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Secondary outcomes

• Short term
• Death, chronic lung disease or major cerebral
  abnormality before hospital discharge
• Significant positive culture after trial entry
• Pneumonia
• NEC
• Duration of respiratory support

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Secondary outcomes

• Long term
• Death before 2 years
• Major disability at 2yrs
• Non-major disability at 2yrs

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Case scenarios
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Eligible?
?

• 29 weeks gestation
• Deterioration day 34
• Recurrent apnoeic episodes
• Prolonged cap. refill time
• CRP 66
• Commenced on antibiotics
• CNS in blood culture

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Eligible?

• Remember
• It is NOT TOO LATE to randomise an infant after a
  positive blood culture has been reported
• IVIG may be of benefit after the inflammatory
  process has begun

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Eligible?
?

• 27 weeks gestation, 1.3kg
• PROM 27 hrs
• GBS on maternal HVS
• Intrapartum antibiotics not given
• Asymptomatic infant
• Antibiotics commenced as hospital policy

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Eligible?

• But
• If there was offensive liquor, raised
  inflammatory markers or this baby was to become
  unwell
• This baby would be eligible for INIS

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Eligible?
?

• Term infant
• Cyanotic episodes at 2hrs age
• Apnoeic requiring ventilation
• CXR patchy consolidation both lung fields
• Commenced on antibiotics
• CRP 19

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Any Questions?Please contact usTel 01865
289741 Email inis_at_npeu.ox.ac.uk
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References

• 1. Murphy DJ, Hope PL, Johnson A. Neonatal risk
  factors for cerebral palsy in very preterm
  babies case-control study. BMJ 1997314404.
• 1. Yoon BH, Romero R, Park JS et al. Fetal
  exposure to an intra-amniotic inflammation and
  the development of cerebral palsy at the age of 3
  years. Am J Obstet Gynecol 182675-681.
• 2. Wu YW. Systematic Review of Chorioamnionitis
  and Cerebral Palsy. Mental Retard Dev
  Disabilities Research Reviews 20028 25-29.
• 3. Damman O, Leviton A. Infection remote from
  the brain, neonatal white matter damage, and
  cerebral palsy in the preterm infant. Semin
  Pediatr Neurol 19985190-201.