Primary objective: -to determine if there is a significant difference in the incidence of oxygen dependency at day 28 and/or death within the first 28 days of life between newborns with congenital diaphragmatic hernia treated with high frequency…
ID
Source
Brief title
Condition
- Respiratory disorders congenital
- Neonatal respiratory disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Oxygen dependency at day 28 and/or death within the first 28 days of life.
Secondary outcome
•Overall mortality in the first year of life
•Number of treatment failures, see paragraph 6.5 failure criteria and switching
•Severity of chronic lung disease using the Bancalari definition (see Appendix
V).
•Number of days on a ventilator
•Severity of pulmonary hypertension according to echocardiographic parameters
•Medical treatment for pulmonary hypertension during the hospital admission
•The level of specific laboratory markers, urine desmosine and proteomic
analysis of tracheal aspirates, up to day 28, to describe the severity of
ventilator-induced lung injury
•Requirement of pulmonary and/or cardiac medication at discharge and/or during
the first year of life
•Long-term pulmonary outcome, described as pulmonary function at the age of 6
and 12 months, diary card documented respiratory morbidity and healthcare
utilisation
•Requirement of ECMO (only described for ECMO-centres)
(see also paragraph 6.1)
Background summary
A congenital diaphragmatic hernia is a congenital defect of the diaphragm,
mostly unilateral, which allows abdominal organs to herniate into the chest
cavity. This results in pulmonary hypoplasia. As a consequence, mechanical
ventilation is needed directly after birth in most cases. Ventilator-induced
lung injury, resulting from prolonged mechanical ventilation, may lead to
bronchopulmonary dysplasia and pulmonary hypertension. This may lead to
prolonged oxygen dependency, use of medication and even death. 33% of patients
with congenital diaphragmatic hernia have bronchopulmonary dysplasia, resulting
from prolonged mechanical ventilation.
There are two ventilation strategies used in newborns having a congenital
diaphragmatic hernia. First, conventional ventilation, may be given. Second,
high frequency oscillatory ventilation may be given. In high frequency
oscillatory ventilation, oxygen is provided by high frequencies, small tidal
volumes and a continuous mean airway pressure. In comparison to conventional
ventilation, fewer fluctuations in pressure exist.
Observational en retrospective studies have suggested high frequency
oscillatory ventilation to reduce barotrauma, to improve survival and to lower
the incidence of chronic lung disease. Still, no prospective randomized
controlled trials have been carried out to compare hogh frequency oscillatory
ventilation and conventional ventilation in children with congenital
diaphragmatic hernia. A prospective randomized controlled trial is needed to
achieve a better understanding of an optimal ventilation strategy to reduce
long-term pulmonary damage in children with congenital diaphragmatic hernia.
(see also paragraph 1, Background)
Study objective
Primary objective:
-to determine if there is a significant difference in the incidence of oxygen
dependency at day 28 and/or death within the first 28 days of life between
newborns with congenital diaphragmatic hernia treated with high frequency
oscillatory ventilation (HFO) and those treated with conventional mechanical
ventilation (CMV) as initial ventilation mode.
The secondary objectives are:
-To compare overall mortality
-To compare the number of treatment failures (see paragraph 6.5 failure
criteria and switching)
-To compare the number of days on the ventilator
-To compare the severity of chronic lung disease according to the Bancalari
definition (see Appendix V)
-To compare the severity of ventilator-induced lung injury by using laboratory
markers for pulmonary vascular endothelial damage and pulmonary hypertension
(see paragraph 6.3)
-To compare the severity of pulmonary hypertension according to
echocardiographic parameters
-To compare the use of medication given for pulmonary hypertension
-To compare the use of pulmonary and/or cardiac medication after discharge
-To compare long-term pulmonary function by using lungfucntion tests at the age
of 6 and 12 months, a patient diary and healthcare questionnaires
-To compare the need for ECMO (only applicable for ECMO-centres)
Study design
This study is designed as a prospective, randomized, multicenter,
international, controlled trial. Within two hours after birth, inborn infants
with an antenatal diagnosis of congenital diaphragmatic hernia will be
randomized to receive either high frequency oscillatory ventilation or
conventional ventilation.
Before birth, parental informed consent will be obtained. Postnatally, infants
will be treated according to standard practice, which is implemented in all
participating centres. Of all patients, demographic and neonatal
characteristics, as well as data on the clinical course and treatment will be
collected in a central database in Rotterdam. An intention-to-treat analysis
will be performed.
(See also paragraph 3, Study design)
Intervention
Conventional mechanical ventilation (CMV) will be provided by a neonatal
ventilator capable of positive pressure ventilation or triggered modes.
High frequency oscillatory ventilation (HFO) will be provided by a high
frequency oscillatory ventilator. HFO is based on high frequencies and small
tidal volumes, together with a continuous mean airway pressure.
Study burden and risks
The purpose of the study is to achieve a better view of optimal ventilation
strategies in children having congenital diaphragmatic hernia in future. If one
of the two ventilation strategies appears to give a better outcome, this may be
of benefit for the children who received this ventilation strategy.
Procedures for the purpose of the study, are of minimal burden for the patient.
Study-related procedures are part of standard care for a newborn with a
congenital diaphragmatic hernia. During the follow-up period, lung function
measurements will be done. Furthermore, parents have to fill in questionaires
and a patient diary.
Dr. Molewaterplein 60
3015 GJ Rotterdam
NL
Dr. Molewaterplein 60
3015 GJ Rotterdam
NL
Listed location countries
Age
Inclusion criteria
•Antenatal diagnosis of congenital diaphragmatic hernia
•Prenatal informed consent
•The children are born in one of the participating centres
•The children are born at or after a gestational age of 34 weeks
•Infants who received a foetal intervention may be included
Exclusion criteria
•Infants with a severe chromosomal anomaly, like trisomy 18 or trisomy 13, which may imply a decision to stop further life-saving medical treatment
•Infants born with a severe cardiac anomaly, expected to need corrective surgery in the first 60 days of life (such as transposition of the great arteries or double outlet right ventricle)
•Infants born with renal anomalies associated with oligohydramnios
•Infants born with severe orthopaedic and skeletal deformities which are likely to influence thoracic and / or lung development (such as chest wall deformities and spine anomalies)
•Infants born with severe anomalies of the central nervous system
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23374.078.08 |