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Risk Factors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations (MALFPULM)

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ClinicalTrials.gov Identifier: NCT02352207
Recruitment Status : Completed
First Posted : February 2, 2015
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date January 5, 2015
First Posted Date February 2, 2015
Last Update Posted Date April 1, 2021
Actual Study Start Date March 17, 2015
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 27, 2015)
Respiratory distress [ Time Frame: At Birth of the child ]
Respiratory distress at birth is defined by a breathing frequency > 60/min, or by the presence of chest retraction signs (Silverman score greater than or equal to 2). At least one of these signs must be persistent at 15' of life
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: March 21, 2019)
  • Necessity of antenatal treatment [ Time Frame: At Birth of the child ]
    Thoracic drainage, amniotic drainage, corticosteroids
  • Therapeutic abortion - fetal death [ Time Frame: At Birth of the child ]
  • Severe respiratory distress [ Time Frame: At Birth of the child ]
    Severe respiratory distress at birth will be defined by the presence of at least one of the following parameters: persistent need at 15' of supplemental oxygen; Persistent need at 15' for a ventilatory support (non-invasive or invasive); neonatal death
  • Identification of KRAS mutation [ Time Frame: 2 years ]
    PCR analysis of known K-RAS mutations in codons 12 and 13
  • Level in delta Forskoline/IBMX Short Circuit Current (µA/cm2) [ Time Frame: 2 years ]
    CFTR activity evaluation
  • CFTR gene expression [ Time Frame: 2 years ]
    quantitative PCR
  • CFTR protein expression [ Time Frame: 2 years ]
    immunohistochemistry
  • Basal short circuit current : Isc Basal [ Time Frame: 2 years ]
  • Effects of other potentiators on CFTR activity : ΔGenistein, ΔVX-770 [ Time Frame: 2 years ]
  • Inhibition of CFTR (inh-172) : ΔInh-172 [ Time Frame: 2 years ]
  • Response to ENaC inhibitors : ΔAmiloride, Δbenzamil [ Time Frame: 2 years ]
  • Activation of Calcium Dependant Channels : ΔUTP [ Time Frame: 2 years ]
  • Inhibition of SLC26A9 : ΔGlyH-101 [ Time Frame: 2 years ]
  • Response to inhibitors of basolateral K+ secretion : ΔBarium ; ΔChromanol [ Time Frame: 2 years ]
  • Secretion of HCO3- in response to forskoline : Δ HCO3- primary culture [ Time Frame: 2 years ]
  • Gene expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1 [ Time Frame: 2 years ]
    quantitative PCR
  • Protein expression of other channels : ENaC, SLC26A9, CaCC, KVLQT1 and KCa3.1 [ Time Frame: 2 years ]
    immunohistochemistry
Original Secondary Outcome Measures
 (submitted: January 27, 2015)
  • Necessity of antenatal treatment [ Time Frame: At Birth of the child ]
    Thoracic drainage, amniotic drainage, corticosteroids
  • Therapeutic abortion - fetal death [ Time Frame: At Birth of the child ]
  • Severe respiratory distress [ Time Frame: At Birth of the child ]
    Severe respiratory distress at birth will be defined by the presence of at least one of the following parameters: persistent need at 15' of supplemental oxygen; Persistent need at 15' for a ventilatory support (non-invasive or invasive); neonatal death
  • Identification of KRAS mutation [ Time Frame: At Birth of the child ]
    PCR analysis of known K-RAS mutations in codons 12 and 13
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Risk Factors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations
Official Title Prospective Identification of Predictors of Neonatal Respiratory Distress for Newborns With Prenatally Diagnosed Congenital Lung Malformations : A Population-based, Nationally Representative Study
Brief Summary

This research focuses on lung malformations detected in fetuses during prenatal ultrasound exams. Pathogenic mechanisms of these rare malformations are poorly understood. Improved knowledge is needed, to give families better information, and to better standardize treatment decisions The main goal is to better predict neonatal complications associated with these malformations, by identifying key predictive markers during the fetal period.

To achieve this objective, it is planned to include 400 pregnant women with prenatal diagnosis of pulmonary malformation in 45 health centers in France. This is the largest study on this topic at the international level.

Detailed Description

The main objective of the study is to develop a prognostic model for estimating the risk of neonatal respiratory distress in children with prenatally diagnosed congenital pulmonary malformation.

The study will be offered to all pregnant women referred to a Center for Prenatal Diagnosis (CPD), due to the identification of a congenital lung malformations in the fetus. This study does not induce any changes in clinical and therapeutic monitoring proposed by the team in charge of the mother. At inclusion, and at each prenatal evaluation, prenatal parameters are entered in an e-CRF. In an effort to minimize any potential intra- and interoperator variability in malformation measurements over time, this study includes a standardized and centralized evaluation of ultrasound and MRI (if available) acquisitions of volume measurements. When the place of delivery is determined, a contact is made before birth with the teams (maternity, neonatology, intensive care unit), so that neonatal data are also collected prospectively. A phone call to the family is planned for the end of the first postnatal month, to identify any respiratory event that would have occurred between returning home after childbirth and the first month.

The routine follow-up of these children is then ensured in accordance with current national recommendations, in conjunction with the reference centers for rare respiratory diseases in children (28 university hospitals, spread across all regions of France). A telephone survey every 6 months with the referring physician in this specialized center or, alternatively, with the family, will collect clinical outcome until the age of 2 years. If a surgical intervention is planned within this interval, consent to collect part of the surgical specimen for research purposes will be solicited. This tissue will be immediately frozen at -80 ° C, to allow laser microdissection and DNA extraction from epithelial cells lining the malformation (Inserm U955). Frozen tissue will be conserved at the biobank of Necker-Enfants Malades.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
A portion of tissue malformation
Sampling Method Non-Probability Sample
Study Population Pregnant women referred to a Center of Prenatal Diagnosis, because of the identification of a pulmonary malformation in the fetus
Condition Foetus With Congenital Pulmonary Malformation
Intervention Other: identification of a pulmonary malformation in the fetus
Study Groups/Cohorts identification of a pulmonary malformation in the fetus
pregnant women referred to a prenatal Center, because of the identification of a pulmonary malformation in the fetus
Intervention: Other: identification of a pulmonary malformation in the fetus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: March 21, 2019)
436
Original Estimated Enrollment
 (submitted: January 27, 2015)
400
Actual Study Completion Date March 10, 2021
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Prenatal identification of a congenital pulmonary malformation (hyperechoic and/or cystic pulmonary lesion)
  • consent of the mother for participation to the study

Exclusion Criteria:

- Absence of consent for participation

Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT02352207
Other Study ID Numbers NI13005
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor Assistance Publique - Hôpitaux de Paris
Collaborators Not Provided
Investigators
Study Director: Laurent SALOMON, MD, PhD Hospital Necker - Enfants Malades
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date March 2021