Official Title: “Early Prevention of Broncho-Pulmonary Dysplasia and Neonatal Mortality in Very Preterm Infants Using Low Dose of Hydrocortisone: a Randomized Controlled Trial”

There is increasing evidence linking a fetal and early neonatal systemic inflammatory response syndrome to the subsequent development of bronchopulmonary dysplasia (BPD) and white matter injury (WMI) in very preterm infants. Babies with evidence of adrenal insufficiency early in life may not be able to control the inflammatory response and are thereby more likely to develop BPD than babies who do not show such evidence of inflammation. We designed a randomized controlled trial to test the hypothesis whether very preterm babies at high-risk of BPD, treated with low doses of HC during the first 10 days of life, are more likely to survive without BPD at 36 weeks of post-menstrual age (PMA), compared to babies treated with placebo.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2012

Individual patients and study procedures. Entry criteria: gestational age between 24 weeks and 27 weeks + 6 days, babies born to mother with either clinical chorioamnionitis, preterm and prelabor rupture of the membranes (PPROM), or preterm labor, written informed consent obtained before inclusion and randomization. Exclusion criteria: babies born with birth weight below the 5th percentile, PPROM before 22 weeks, major fetal anomaly or congenital malformation, mother refusal or inability to provide consent. Stratification: stratum A:

24-25 weeks and stratum B: 26-27 weeks. Centrally controlled randomization takes place between 12 and 48 hours of age and patients assigned to the HC group are treated with 0,5 mg/kg HC intravenously twice a day for seven days and once a day for the next three days.

Ibuprofen is only given to babies with persistent ductus arteriosus (PDA) echocardiographically confirmed at 24 hours of age or older.

Outcome variables. The primary outcome is a dichotomous variable: survival without BPD at 36 weeks PMA. A consistent physiologic definition of BPD will be used by all participating centres (Walsh MC, Pediatrics 2004;114:1305-11). Secondary outcome variables include features of WMI on MRI performed at 40 weeks PMA and neurodevelopmental outcome at 2-year of corrected age. Other outcome variables include death before discharge, BPD at 28 days and 36 weeks, duration of mechanical ventilation and O2 supplementation, need for vasopressors, use of open-labeled postnatal steroids (HC or dexamethasone), confirmed or suspected early and late onset sepsis, PDA, gastrointestinal perforation, NEC, ROP, IVH, biological markers of the neonatal inflammatory response syndrome.

Intervention(s) in this Clinical Trial

• Drug: hydrocortisone
  • Intravenous slow of hemisuccinate hydrocortisone 0.5 mg/kg/12 hours during 7 days then 0.5mg/kg/24 hours during 3 days.
• Drug: placebo
  • intravenous slow of placebo 0.5mg/kg/12 hours during 7 days then 0.5 mg/kg/24 hours during 3 days

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • 1: active arm treated with low doses of HC during the first 10 days of life
• Placebo Comparator: 2
  • 2:placebo arm treated with placebo at the same conditions than active arm

Primary Measures

• dichotomous variable: survival without BPD at 36 weeks PMA.
  • Time Frame: add 8 to12
    Safety Issue?: No

Secondary Measures

• features of WMI on MRI performed between 36-40 weeks PMA
  • Time Frame: 8-12 weeks
    Safety Issue?: No
• neurodevelopmental outcome
  • Time Frame: 18 month-3 years
    Safety Issue?: Yes
• Death before discharge
  • Time Frame: discharge
    Safety Issue?: No
• BPD 28 days and 36 weeks
  • Time Frame: 28 days and 36 weeks
    Safety Issue?: No
• duration of mechanical ventilation and O2 supplementation
  • Time Frame: inclusion to discharge
    Safety Issue?: No
• need for vasopressors
  • Time Frame: inclusion to discharge
    Safety Issue?: No

Inclusion Criteria:

• Gestational age between 24 weeks and 27 weeks + 6 days
• Babies born to mother with either clinical chorioamnionitis, preterm and prelabor rupture of the membranes (PPROM), or preterm labor
• Written informed consent obtained before inclusion and randomization.

Exclusion Criteria:

• Babies born to mothers with birth weight below the 5th percentile
• PPROM before 22 weeks
• Major fetal anomaly or congenital malformation
• Mother refusal or inability to provide consent.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 24 Hours

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

olivier BAUD, Pr Principal Investigator ASSISTANCE PULIQUE HOPITAUX DE PARIS  

Overall Contact: Olivier BAUD, Pr 01 40 03 41 09 olivier.baud@rdb.aphp.fr

Information obtained from ClinicalTrials.gov on August 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00623740

Study ID Number: P 060250

ClinicalTrials.gov Identifier: NCT00623740

Health Authority: France: Ministry of Health