PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates

NCT ID: NCT00623740

Last Updated: 2018-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 523 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2016-01-31

Brief 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.

Detailed 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.

Conditions

Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1: hydrocortisone

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

Group Type: EXPERIMENTAL

hydrocortisone

Intervention Type: DRUG

Intravenous slow of hemisuccinate hydrocortisone 0.5 mg/kg/12 hours during 7 days then 0.5mg/kg/24 hours during 3 days.

2: Placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

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

Interventions

hydrocortisone

Intravenous slow of hemisuccinate hydrocortisone 0.5 mg/kg/12 hours during 7 days then 0.5mg/kg/24 hours during 3 days.

Intervention Type: DRUG

placebo

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

Intervention Type: DRUG

Other Intervention Names

hydrocortisone upjohn 100mg

Eligibility Criteria

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.

• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

olivier BAUD, Pr

Role: PRINCIPAL_INVESTIGATOR

ASSISTANCE PULIQUE HOPITAUX DE PARIS

Locations

Hopital Robert Debre

Paris, , France

Countries

France

References

Baud O. [Postnatal steroid treatment in preterm infants: risk/benefit ratio]. J Gynecol Obstet Biol Reprod (Paris). 2005 Feb;34(1 Suppl):S118-26. doi: 10.1016/s0368-2315(05)82698-5. French.

Reference Type: RESULT

PMID: 15767942 (View on PubMed)

Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, Zupan-Simunek V, Coursol A, Beuchee A, Bolot P, Andrini P, Mohamed D, Alberti C; PREMILOC trial study group. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016 Apr 30;387(10030):1827-36. doi: 10.1016/S0140-6736(16)00202-6. Epub 2016 Feb 23.

Reference Type: RESULT

PMID: 26916176 (View on PubMed)

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. doi: 10.1001/jama.2017.2692.

Reference Type: RESULT

PMID: 28384828 (View on PubMed)

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. No abstract available.

Reference Type: RESULT

PMID: 27650090 (View on PubMed)

Baud O, Lehert P; PREMILOC study group. Prophylactic hydrocortisone and the risk of sepsis in neonates born extremely preterm. Eur J Pediatr. 2025 Jun 14;184(7):419. doi: 10.1007/s00431-025-06248-9.

Reference Type: DERIVED

PMID: 40515786 (View on PubMed)

Baud O, Lehert P; PREMILOC study group. Bronchopulmonary dysplasia to predict neurodevelopmental impairment in infants born extremely preterm. Pediatr Res. 2025 Jun;97(7):2436-2442. doi: 10.1038/s41390-024-03601-w. Epub 2024 Oct 24.

Reference Type: DERIVED

PMID: 39448816 (View on PubMed)

Baud O, Lehert P; PREMILOC study group. The beneficial effect of prophylactic hydrocortisone treatment in extremely preterm infants improves upon adjustment of the baseline characteristics. Pediatr Res. 2024 Jan;95(1):251-256. doi: 10.1038/s41390-023-02785-x. Epub 2023 Aug 31.

Reference Type: DERIVED

PMID: 37653218 (View on PubMed)

Trousson C, Toumazi A, Bourmaud A, Biran V, Baud O. Neurocognitive outcomes at age 5 years after prophylactic hydrocortisone in infants born extremely preterm. Dev Med Child Neurol. 2023 Jul;65(7):926-932. doi: 10.1111/dmcn.15470. Epub 2022 Nov 23.

Reference Type: DERIVED

PMID: 36417367 (View on PubMed)

Renolleau C, Toumazi A, Bourmaud A, Benoist JF, Chevenne D, Mohamed D, Alberti C, Biran V, Baud O; PREMILOC Trial Study Group. Association between Baseline Cortisol Serum Concentrations and the Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants. J Pediatr. 2021 Jul;234:65-70.e3. doi: 10.1016/j.jpeds.2020.12.057. Epub 2020 Dec 24.

Reference Type: DERIVED

PMID: 33359303 (View on PubMed)

Alison M, Tilea B, Toumazi A, Biran V, Mohamed D, Alberti C, Bourmaud A, Baud O; PREMILOC Trial group. Prophylactic hydrocortisone in extremely preterm infants and brain MRI abnormality. Arch Dis Child Fetal Neonatal Ed. 2020 Sep;105(5):520-525. doi: 10.1136/archdischild-2019-317720. Epub 2020 Jan 24.

Reference Type: DERIVED

PMID: 31980445 (View on PubMed)

Heneau A, Guimiot F, Mohamed D, Rideau Batista Novais A, Alberti C, Baud O; PREMILOC Trial study group. Placental Findings and Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants. Pediatrics. 2018 Feb;141(2):e20171788. doi: 10.1542/peds.2017-1788. Epub 2018 Jan 18.

Reference Type: DERIVED

PMID: 29348196 (View on PubMed)

Other Identifiers

2007-002041-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P 060250

Identifier Type: -

Identifier Source: org_study_id