Bronchopulmonary DysplasiaPhase 3PREMILOCNCT00623740
PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates
A Phase 3 study testing hydrocortisone in people with Bronchopulmonary Dysplasia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- Bronchopulmonary Dysplasia
- What is being tested?
- hydrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 523 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2008to Jan 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- hydrocortisone, placebo
- Keywords
- Hydrocortisone, Very low birth weight, Bronchopulmonary dysplasia, Prevention Cerebral palsy
- Medical subject headings
- Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydrocortisoneDrug
Also called hydrocortisone upjohn 100mg
Intravenous slow of hemisuccinate hydrocortisone 0.5 mg/kg/12 hours during 7 days then 0.5mg/kg/24 hours during 3 days.
placeboDrug
intravenous slow of placebo 0.5mg/kg/12 hours during 7 days then 0.5 mg/kg/24 hours during 3 days
| Study group | Role | What they receive |
|---|---|---|
| 1: hydrocortisone | Experimental | 1: active arm treated with low doses of HC during the first 10 days of life Receives: Drug: hydrocortisone |
| 2: Placebo | Placebo comparator | 2:placebo arm treated with placebo at the same conditions than active arm Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
dichotomous variable: survival without BPD at 36 weeks PMA.
Measured: add 8 to12
Secondary outcomes (6)
features of WMI on MRI performed between 36-40 weeks PMA
Measured: 8-12 weeks
neurodevelopmental outcome
Measured: 18 month-3 years
Death before discharge
Measured: discharge
BPD 28 days and 36 weeks
Measured: 28 days and 36 weeks
duration of mechanical ventilation and O2 supplementation
Measured: inclusion to discharge
need for vasopressors
Measured: inclusion to discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2008 (estimated)
- Study startApr 2008
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 523 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- olivier BAUD, Pr, Principal investigator, ASSISTANCE PULIQUE HOPITAUX DE PARIS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00623740
- Sponsor's protocol ID
- P 060250
- Other IDs
- 2007-002041-20
- Acronym
- PREMILOC
- Status last verified
- Aug 2016
- First submitted
- 7 Feb 2008
- Last updated
- 2 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15767942Baud 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.
PubMed 26916176Baud 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.
PubMed 28384828Baud 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.
PubMed 27650090Baud 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.
PubMed 40515786Baud 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.
PubMed 39448816Baud 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.
PubMed 37653218Trousson 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.
PubMed 36417367Renolleau 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.
PubMed 33359303Alison 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.
PubMed 31980445Heneau 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.
PubMed 29348196
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Prevention of Broncho-pulmonary Dysplasia and Neonatal Mortality in Very Preterm Infants Using Low Dose of Hydrocortisone: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00623740
- Acronym / sponsor ID
- PREMILOC / P 060250
- Conditions
- Bronchopulmonary Dysplasia
- Keywords
- Hydrocortisone, Very low birth weight, Bronchopulmonary dysplasia, Prevention Cerebral palsy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 523 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 26 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: hydrocortisone | Experimental | Drug: hydrocortisone1: active arm treated with low doses of HC during the first 10 days of life |
| 2: Placebo | Placebo comparator | Drug: placebo2:placebo arm treated with placebo at the same conditions than active arm |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydrocortisoneAlso: hydrocortisone upjohn 100mgIntravenous slow of hemisuccinate hydrocortisone 0.5 mg/kg/12 hours during 7 days then 0.5mg/kg/24 hours during 3 days. | Drug | 1: hydrocortisone |
| placebointravenous slow of placebo 0.5mg/kg/12 hours during 7 days then 0.5 mg/kg/24 hours during 3 days | Drug | 2: Placebo |
Primary outcome
dichotomous variable: survival without BPD at 36 weeks PMA.
Time frame: add 8 to12
6 secondary outcomes
features of WMI on MRI performed between 36-40 weeks PMA
Time frame: 8-12 weeks
neurodevelopmental outcome
Time frame: 18 month-3 years
Death before discharge
Time frame: discharge
BPD 28 days and 36 weeks
Time frame: 28 days and 36 weeks
duration of mechanical ventilation and O2 supplementation
Time frame: inclusion to discharge
need for vasopressors
Time frame: inclusion to discharge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
- Results publication: PubMed 15767942Baud 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.
- Results publication: PubMed 26916176Baud 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.
- Results publication: PubMed 28384828Baud 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.
- Results publication: PubMed 27650090Baud 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.
- Derived from this study: PubMed 40515786Baud 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.
- Derived from this study: PubMed 39448816Baud 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.
- Derived from this study: PubMed 37653218Baud 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.
- Derived from this study: PubMed 36417367Trousson 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.
- Derived from this study: PubMed 33359303Renolleau 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.
- Derived from this study: PubMed 31980445Alison 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.
- Derived from this study: PubMed 29348196Heneau 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
olivier BAUD, Pr principal investigator
ASSISTANCE PULIQUE HOPITAUX DE PARIS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing hydrocortisone in people with Bronchopulmonary Dysplasia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
dichotomous variable: survival without BPD at 36 weeks PMA. (time frame: add 8 to12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00623740, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2018.