IV sildenafil is superior to iNO for the treatment of pulmonary hypertension in CDH newborns and should be considered as the drug of first choice in the future
ID
Source
Brief title
Condition
- Neonatal respiratory disorders
Synonym
Health condition
congenital diaphragmatic hernia pulmonary hypertension newborn congenitale hernia diafragmatica pulmonale hypertensie pasgeborenen
Research involving
Sponsors and support
CDH UK the congenital diaphragmatic hernia charity
Intervention
Outcome measures
Primary outcome
The absence of pulmonary hypertension on echocardiography on day 14 without pulmonary vasodilator therapy and without treatment failure in patients and/or death within the first 28 days of life
Secondary outcome
• Oxygenation index
• Overall mortality
• Incidence of treatment failure
• Time on intervention drug (intervention drug free days on day 14)
• Vasoactive-inotropic support score
• Need for ECMO
• Ventilator free days on day 28
• Severity of pulmonary hypertension, using laboratory markers and tracheal aspirates for proteomic, metabolomics and biochemical analysis as a marker
• The use of other medication given for pulmonary hypertension during the hospital admission
• The use of pulmonary and/or cardiac medication at discharge and its total duration
• Long-term pulmonary hypertension on echocardiography at 6 and 12 months
• Chronic lung disease
• The development of neurological abnormalities evaluated with ultrasound of the brain
• External validation of sildenafil PKPD model
Background summary
significant PH is present. The patient can participate in the trial within the first seven days of
life. Inhaled NO will be given with a starting dose of 20 ppm. Inhaled nitric oxide will be
provided by a tank connected to a neonatal ventilator. Therefore, the study will be open
label. Sildenafil with be given intravenously, using a loading dose of 0.4mg/kg in 3 hours,
followed by continuous infusion of 1.6mg/kg/day. The patients will be treated according to
the standard protocol for patients with CDH, which is implemented in all participating centers
according to the revised CDH consortium guidelines. Strict guidelines for cardiovascular
support will be used. Echocardiography will be performed to determine eligibility of entry into
the study at day 1,and subsequently before study drug administration, on day 14, day 28 (or
discharge whichever is sooner) and at follow up at 6 and 12 months. The echocardiographic
images will be collected for centralized, blinded analysis of pulmonary artery pressure and
cardiac function by 2 investigators. Demographic and neonatal characteristics as well as data on the clinical course and treatment of all patients will be collected in a central database in
Rotterdam. Because all patients will be analyzed on the basis of intention-to-treat, data after
treatment failure will be collected in a similar way for all included patients.
Study objective
and should be considered as the drug of first choice in the future
Study design
Intervention
>
Study burden and risks
Extra blood taken and extra echocardiograms made
Postbus 2060
S.C.M. Cochius - den Otter
Rotterdam 3000CB
The Netherlands
+31 10 7040704
codinos@erasmusmc.nl
Postbus 2060
S.C.M. Cochius - den Otter
Rotterdam 3000CB
The Netherlands
+31 10 7040704
codinos@erasmusmc.nl
Age
Inclusion criteria
Diagnosis of CDH and pulmonary hypertension defined as 2 of the following 4 criteria:
I. Systolic PAP> 2/3 systemic systolic pressure estimated by echocardiography
II. RV dilatation/septal displacement, RV dysfunction +/- LV dysfunction
III. Pre-post ductal SpO2 difference > 10%
IV. OI>20.
Parental informed consent
Children born at or after a gestational age of 34 weeks
Newborns who received a fetal intervention may be included
Exclusion criteria
Severe chromosomal anomaly, like trisomy 18 or trisomy 13, which may imply a decision to stop or not to start life-saving medical treatment Severe cardiac anomaly, expected to need corrective surgery in the first 60 days of life (such as transposition of the great arteries, truncus arteriosus, coarctation aortae or double outlet right ventricle)
Renal anomalies associated with oligohydramnios Severe orthopaedic and skeletal deformities, which are likely to influence thoracic, and / or lung development (such as chest wall deformities and spine anomalies)
Severe anomalies of the central nervous system Patients born in another centre, transported with iNO
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL6796 |
| NTR-old | NTR6982 |
| CCMO | NL60229.078.17 |
| EudraCT | 2017-000421-13 |
| OMON | NL-OMON50767 |