PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates

NCT00623740 | Completed Phase 3 DMC

• 2 other identifiers: P 0602502007-002041-20
• Study Type: interventional
• Target: 523
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchopulmonary Dysplasia

Keywords

Hydrocortisone; Very low birth weight; Bronchopulmonary dysplasia; Prevention Cerebral palsy

Outcome Measures

Primary Outcomes (1)

• dichotomous variable: survival without BPD at 36 weeks PMA.

  add 8 to12

Secondary Outcomes (6)

• features of WMI on MRI performed between 36-40 weeks PMA

  8-12 weeks

• neurodevelopmental outcome

  18 month-3 years

• Death before discharge

  discharge

• BPD 28 days and 36 weeks

  28 days and 36 weeks

• duration of mechanical ventilation and O2 supplementation

  inclusion to discharge

Study Arms (2)

1: hydrocortisone

EXPERIMENTAL

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

Drug: hydrocortisone

2: Placebo

PLACEBO COMPARATOR

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

Drug: placebo

Interventions

hydrocortisone DRUG

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

Also known as: hydrocortisone upjohn 100mg

1: hydrocortisone

placebo DRUG

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

2: Placebo

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Robert Debre

Paris, 75019, France

Location

Related Publications (11)

• 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.

  PMID: 15767942 RESULT

• 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.

  PMID: 26916176 RESULT

• 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.

  PMID: 28384828 RESULT

• 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.

  PMID: 27650090 RESULT

• 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.

  PMID: 40515786 DERIVED

• 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.

  PMID: 39448816 DERIVED

• 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.

  PMID: 37653218 DERIVED

• 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.

  PMID: 36417367 DERIVED

• 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.

  PMID: 33359303 DERIVED

• 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.

  PMID: 31980445 DERIVED

• 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.

  PMID: 29348196 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• olivier BAUD, Pr

  ASSISTANCE PULIQUE HOPITAUX DE PARIS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2008
• First Posted: February 26, 2008
• Study Start: April 1, 2008
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: October 2, 2018

Record last verified: 2016-08

Locations

FR (1)