PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Bronchopulmonary Dysplasia

Treatments: Drug: hydrocortisone; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00623740

P 060250

2007-002041-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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 3th 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 arteriosis (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.

Enrollment: 523 patients

Sex: All

Ages: Under 24 hours old

Volunteers: No Healthy Volunteers

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 3th percentile
• PPROM before 22 weeks
• Major fetal anomaly or congenital malformation
• Mother refusal or inability to provide consent.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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523 participants in 2 patient groups, including a placebo group

1: hydrocortisone

Experimental group

Description:

1: active arm treated with low doses of HC during the first 10 days of life

Treatment:

Drug: hydrocortisone

2: Placebo

Placebo Comparator group

Description:

2:placebo arm treated with placebo at the same conditions than active arm

Treatment:

Drug: placebo