Protein C in NEC V1

• Research type

  Research Study

• Full title

  Protein C in neonatal Necrotising Enterocolitis: a dose-finding, open-label, pilot study

• IRAS ID

  55743

• Contact name

  Paula Lister

• Sponsor organisation

  Great Ormond Street Hospital and Institute of Child Health

• Eudract number

  2010-021254-19

• ISRCTN Number

  n/a

• Research summary

  This is an open-label pilot study to determine the optimum dose of protein C concentrate required (CEPROTIN) to increase plasma protein C levels to > 0.8IU/mL in neonates with necrotising enterocolitis (NEC) for 7 days. NEC is an inflammatory bowel disease. It is the commonest reason for emergency surgery in neonates. Around 30-50% of affected infants die, and survivors often have poor neurodevelopmental outcomes. Microscopic clots reduce blood flow to the intestine in NEC. Pro and anticoagulant proteins are balanced in adults, but neonates, especially preterms, are relatively deficient in anti-coagulation proteins. This means clots form readily at sites of inflammation and worsen gut injury. Restoration of Protein C balance may be therapeutic in neonates with NEC by preventing excessive clot formation. The dose required is not known. This is a new indication for CEPROTIN in this population. CEPROTIN is licensed in Europe for use in neonates with congenital protein c deficiency, a fatal condition. This study has 4 sequential, dose-escalating groups of 5 participants. Participants will receive study interventions in addition to standard NEC therapy. Protein C will be administered 6-hourly using pre-existing intravenous lines for 7 days. Group 1 has no intervention to determine the unknown, natural recovery period of infants' own protein C. Data from groups 2 (50 IU/kg/dose) and 3 (100 IU/kg/dose) be reviewed by an independent data monitoring committee before moving to the next dose group. The highest dose (group 4, 150 IU/kg/dose) has been used safely in newborns. The primary outcome is plasma protein c level. Trends in secondary outcome parameters (inflammatory and coagulation markers, transfusion requirements, severity of illness, time to recovery) will be explored to assist in the development of future trials.

• REC name

  London - Hampstead Research Ethics Committee

• REC reference

  11/LO/1655

• Date of REC Opinion

  5 Dec 2011

• REC opinion

  Further Information Favourable Opinion