international neonatal immunotherapy study national perinatal epidemiology unit oxford
TRANSCRIPT
International Neonatal Immunotherapy Study
National Perinatal Epidemiology Unit
Oxford
www.npeu.ox.ac.uk
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)
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
INIS Co-ordinating Team
Peter Brocklehurst Chief InvestigatorBarbara Farrell Trial DirectorClare Shakeshaft Study Co-ordinatorCaroline Wilson Follow up Co-ordinatorAndy King ProgrammerRui Zhao Data AssistantEllie Morgan-Jones Administrative Assistant
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
INIS - study design
• Gold standard for treatment trials
• Double-blind
• Randomised
• Placebo -controlled
Receiving antibiotics and proven or
suspected serious infection
Mortality or major disability
IVIG
at 2 years
Placebo
Eligibility criteria2. At least one of the following:
birth weight less than 1500greceiving respiratory support via an
endotracheal tube evidence of infection in blood culture, CSF or
usually sterile body fluid
AND………
Exclusion criteria
• IVIG already given*
• IVIG thought to be needed or contraindicated
*specific IVIG
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
Eligibility - age
• Babies at any age whilst resident on NICU
• After discharge babies are eligible until EDD plus 28 days
Consent
• Consent must be fully informed and obtained before randomisation
• Use the Information Leaflet
• Direct parents to website or INIS contact
Randomisation
• Simple, no phone call required
• Drug boxes in pre-randomised sequence
• Use lowest numbered box
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
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
Secondary outcomes
• Long term– Death before 2 years– Major disability at 2yrs– Non-major disability at 2yrs
Eligible?
• 29 weeks gestation• Deterioration day 34• Recurrent apnoeic episodes• Prolonged cap. refill time• CRP 66• Commenced on antibiotics • CNS in blood culture
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
Eligible?
• 27 weeks gestation, 1.3kg
• PROM 27 hrs
• GBS on maternal HVS
• Intrapartum antibiotics not given
• Asymptomatic infant
• Antibiotics commenced as hospital policy
Eligible?
But
• If there was offensive liquor, raised inflammatory markers or this baby was to become unwell
This baby would be eligible for INIS
Eligible?
• Term infant
• Cyanotic episodes at 2hrs age
• Apnoeic requiring ventilation
• CXR patchy consolidation both lung fields
• Commenced on antibiotics
• CRP 19
References
1. Murphy DJ, Hope PL, Johnson A. Neonatal risk factors for cerebral palsy in very preterm babies: case-control study. BMJ 1997;314:404.
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 182:675-681.
2. Wu YW. Systematic Review of Chorioamnionitis and Cerebral Palsy. Mental Retard Dev Disabilities Research Reviews 2002;8: 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 1998;5:190-201.