PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates

Bronchopulmonary Dysplasia Clinical Trial

— PREMILOC  

Official title:

Early Prevention of Broncho-pulmonary Dysplasia and Neonatal Mortality in Very Preterm Infants Using Low Dose of Hydrocortisone: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00623740
• Other study ID #: P 060250
• Secondary ID: 2007-002041-20
• Status: Completed
• Phase: Phase 3
• Start date: April 2008
• Est. completion date: January 2016

Study information

• Verified date: August 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 523
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Hyperplasia

Intervention

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.
• placebo
intravenous slow of placebo 0.5mg/kg/12 hours during 7 days then 0.5 mg/kg/24 hours during 3 days

Locations

Country	Name	City	State
France	Hopital Robert Debre	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (4)

Baud O, Alberti C, Mohamed D, Watterberg K. Low-dose hydrocortisone in extremely preterm infants - Authors' reply. Lancet. 2016 Sep 17;388(10050):1158-9. doi: 10.1016/S0140-6736(16)31611-7. Epub 2016 Sep 16. — View Citation

Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, Zupan-Simunek V, Coursol A, Beuchée A, Bolot P, Andrini P, Mohamed D, Alberti C; PREMILOC trial study group. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dyspla — View Citation

Baud O, Trousson C, Biran V, Leroy E, Mohamed D, Alberti C; PREMILOC Trial Group. Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age. JAMA. 2017 Apr 4;317(13):1329-1337 — View Citation

Baud O. [Postnatal steroid treatment in preterm infants: risk/benefit ratio]. J Gynecol Obstet Biol Reprod (Paris). 2005 Feb;34(1 Suppl):S118-26. Review. French. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	dichotomous variable: survival without BPD at 36 weeks PMA.		add 8 to12
Secondary	features of WMI on MRI performed between 36-40 weeks PMA		8-12 weeks
Secondary	neurodevelopmental outcome		18 month-3 years
Secondary	Death before discharge		discharge
Secondary	BPD 28 days and 36 weeks		28 days and 36 weeks
Secondary	duration of mechanical ventilation and O2 supplementation		inclusion to discharge
Secondary	need for vasopressors		inclusion to discharge