Congenital diaphragmatic hernia with pulmonary hypertension
Conditions
Interventions
Trade Name: revatio 0.8mg/ml solution for injection
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Sildenafil
CAS Number: 171599-83-0
Concentration unit: mg/kg milligram(s)/
Sponsors
Erasmus MC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of CDH and pulmonary hypertension defined as 2 of the following 4 criteria: I. PAP> 2/3 systemic 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 Are the trial subjects under 18? yes Number of subjects for this age range: 330 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine if there is a difference in the incidence of pulmonary hypertension in the absence of pulmonary vasodilator therapy on day 14 on echocardiography and/or death within the first 28 days of life between CDH patients treated with iNO versus those treated with intravenous sildenafil. ;Secondary Objective: The secondary objectives are: •To compare the change in oxygenation index before and after start treatment •To compare overall mortality •To compare the incidence of treatment failure (see paragraph 6.5) •To compare the time on intervention drug •To compare the need for ECMO •To compare the number of ventilator free days at day 28 •To compare the vasoactive-inotropic support score before and after starting the intervention drug •To compare laboratory markers for pulmonary vascular endothelial damage and pulmonary hypertension (see paragraph 6.3) •To compare the use of other medication given for pulmonary hypertension •To compare the use of pulmonary and/or cardiac medication after discharge •To compare the incidence of long-term pulmonary hypertension at the age of 1 year •To compare the incidence of chronic lung disease ;Primary end point(s): The main study endpoint is pulmonary hypertension in the absence of pulmonary vasodilator therapy on echocardiography on day 14 and/or death within the first 28 days of life ;Timepoint(s) of evaluation of this end point: Day 14 and day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in oxygenation index after 12 hours of treatment • Overall mortality in the first year of life • Requirement of ECMO (only for ECMO centres) • Treatment failure (see paragraph 6.5, failure criteria) • Severity and presence of pulmonary hypertension on day 1 and/or just before starting the study drug, on day 14, on day 28 or at discharge (whatever comes first), at 6 months and 1 year according to the following echocardiographic parameters as described by the cardiologist: PAP 2/3 systemic pressure, RV dilatation/septal displacement, RV dysfunction +/- LV dysfunction. (see Case Record Form) • Number ventilator free days on day 28 (deaths are counted as worst outcome) • Number of intervention drug free days on day 14 • Fraction of days requiring medical treatment for pulmonary hypertension during the hospital admission, described as the use of iNO, sildenafil, prostanoids, endothelin 1 antagonists, and/or other medication for pulmonary hypertension • The level of specific laboratory markers and urine, up to day 28, to describe the severity and presence of pulmonary hypertension. • Vasoactive-inotropic support score before and 12 hours after starting study medication. This score is calculated with: (dopamine (mcg/kg/min) + dobutamine (mcg/kg/min) + 100x adrenaline (mcg/kg/min) + 10x milrinone (mcg/kg/min) + 10.000x vasopressin (U/kg/min) + 100x noradrenaline (mcg/kg/min)) [31] • Requirement of PH medication, described as oral sildenafil, bosentan and/or a prostanoid at discharge and/or during the first year of life. • Severity of chronic lung disease using need for oxygen on day 28 and 56. • Long-term pulmonary hypertension using echocardiography at the age of 6 and 12 months. • The development of neurological abnormalities evaluated with an ultrasound of the brain before start of intervention drug, after surgery and before discharge. ;Timepoint(s) of evaluation of this end point: 12 and 24 hours day of surgery and day after surg | — |
Countries
Austria, Belgium, Italy, Netherlands, Norway, Sweden
Contacts
Public Contactproject leader
Erasmus MC
Outcome results
None listed