PREMILOC Trial to Prevent Bronchopulmonary Dysplasia in Very Preterm Neonates

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00623740
First received: February 7, 2008
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Bronchopulmonary Dysplasia
Drug: hydrocortisone
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Early Prevention of Broncho-pulmonary Dysplasia and Neonatal Mortality in Very Preterm Infants Using Low Dose of Hydrocortisone: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • dichotomous variable: survival without BPD at 36 weeks PMA. [ Time Frame: add 8 to12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • features of WMI on MRI performed between 36-40 weeks PMA [ Time Frame: 8-12 weeks ] [ Designated as safety issue: No ]
  • neurodevelopmental outcome [ Time Frame: 18 month-3 years ] [ Designated as safety issue: Yes ]
  • Death before discharge [ Time Frame: discharge ] [ Designated as safety issue: No ]
  • BPD 28 days and 36 weeks [ Time Frame: 28 days and 36 weeks ] [ Designated as safety issue: No ]
  • duration of mechanical ventilation and O2 supplementation [ Time Frame: inclusion to discharge ] [ Designated as safety issue: No ]
  • need for vasopressors [ Time Frame: inclusion to discharge ] [ Designated as safety issue: No ]

Estimated Enrollment: 786
Study Start Date: April 2008
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: hydrocortisone
1: active arm treated with low doses of HC during the first 10 days of life
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.
Other Name: hydrocortisone upjohn 100mg
Placebo Comparator: 2: Placebo
2:placebo arm treated with placebo at the same conditions than active arm
Drug: placebo
intravenous slow of placebo 0.5mg/kg/12 hours during 7 days then 0.5 mg/kg/24 hours during 3 days

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.

  Eligibility

Ages Eligible for Study:   up to 24 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623740

Contacts
Contact: Olivier BAUD, Pr 01 40 03 41 09 olivier.baud@rdb.aphp.fr

Locations
France
Hopital Robert Debre Recruiting
Paris, France, 75019
Contact: Olivier BAUD, Pr    +33(0)1 40 03 41 09    olivier.baud@rdb.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: olivier BAUD, Pr ASSISTANCE PULIQUE HOPITAUX DE PARIS
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00623740     History of Changes
Other Study ID Numbers: P 060250, 2007-002041-20
Study First Received: February 7, 2008
Last Updated: September 17, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Hydrocortisone
Very low birth weight
Bronchopulmonary dysplasia
Prevention Cerebral palsy

Additional relevant MeSH terms:
Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on October 16, 2014