Patent Ductus Arteriosus (PDA) Neonatal Diseases
Conditions
Interventions
Current interventions as of 10/04/2014:
This trial is intending to treat infants in the same window as the prophylaxis trials using ibuprofen with recommended doses as per study protocol. Patients wil
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Age
0 Days to 3 Days
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 03/08/2023: 1. Born at 23+0 to 28+6 weeks of gestation 2. Less than 72 hours old 3. Confirmed by echocardiography to have a large PDA which is at least 1.5 mm in diameter (determined by gain optimised colour Doppler) AND has unrestrictive pulsatile (left to right) flow (ratio of flow velocity in PDA Maximum (Vmax) to Minimum (Vmin) > 2:1)) or, growing flow pattern (< 30% right to left), and no clinical concerns of pulmonary hypertension 4. The responsible clinician is uncertain about whether this baby might benefit from treatment to close the PDA 5. Written informed consent has been obtained from the parent(s) _____ Previous inclusion criteria as of 10/04/2014: 1. Born at 23+0 to 28+6 weeks of gestation 2. Less than 72 hours old 3. Confirmed by echocardiography to have a large PDA which is at least 1.5 mm in diameter (determined by gain optimised colour Doppler) AND has unrestrictive pulsatile left to right flow 4. The responsible clinician is uncertain about whether this baby might benefit from treatment to close the PDA 5. Written informed consent has been obtained from the parent(s) _____ Previous inclusion criteria: 1. Preterm infants born between 23+0 and 28+6 weeks gestation 2. Echocardiographic assessment within 24 hours of birth meeting the enrolment criteria 3. Signed parental consent
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 03/08/2023: 1. No realistic prospect of survival 2. Severe congenital anomaly 3. Clinical or echocardiography suspicion of congenital structural heart disease that contraindicates treatment with ibuprofen 4. Other conditions that would contraindicate the use of ibuprofen (active bleeding especially intracranial or gastrointestinal bleeding, coagulopathy, thrombocytopenia (platelet count <50,000), renal failure, life threatening infection, pulmonary hypertension, known or suspected necrotising enterocolitis (NEC)) 5. Indomethacin, ibuprofen, or paracetamol administration after birth _____ Previous exclusion criteria as of 10/04/2014: 1. No realistic prospect of survival 2. Severe congenital anomaly 3. Structural heart disease requiring treatment 4. Other conditions that would contraindicate the use of ibuprofen (clinically significant intracranial or gastrointestinal haemorrhage, coagulopathy, thrombocytopenia [platelet count <50,000], renal failure, pulmonary hypertension, known or suspected necrotising enterocolitis [NEC]) 5. Antenatal exposure to cyclo-oxygenase (COX) inhibitors 6. Received indomethacin, ibuprofen or paracetamol administration after birth _____ Previous exclusion criteria: 1. Baby clinically unstable and not expected to survive 2. Congenital anomalies predicted to influence neurodevelopmental outcome 3. Structural heart disease 4. Contraindication to use of ibuprofen (platelet count <50,000) 5. Unlikely to commence first dose of treatment by 24 hours of age
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 03/08/2023: The primary outcome is defined as a composite outcome of death by 36 weeks postmenstrual age or moderate or severe BPD at 36 weeks post-menstrual age. Severity-Based Diagnostic Criteria for BPD is defined as: Therapy with oxygen >21% and/or respiratory support for =28 days and the following: Mild BPD: Baby is breathing room air Moderate BPD: Baby is in 22–29% oxygen, or 0.01–1.0 L/min Severe BPD: FiO2 =0.3, or low flow oxygen =1.1 L/min, or the baby is receiving any respiratory support (ventilation, CPAP, or high flow oxygen therapy) to achieve saturations of = 91% The need for oxygen is subjective and hence oxygen dependency is confirmed using an ‘oxygen reduction test’. This is based on the threshold at which the baby is able to maintain oxygen saturations =91% whilst breathing in air or at a given minimum FiO2. Babies unable to achieve this are considered to be oxygen-dependent. This test only applies to those babies whose oxygen requirements are <0.3, or low flow oxygen <1.1L/min, and who have not received any additional respiratory support in the previous 24h. Babies outside of this are not tested, but data on their oxygen requirements will be collected. _____ Previous primary outcome measures as of 10/04/2014: The primary outcome is defined as a composite outcome of death or BPD at 36 weeks post-menstrual age. BPD is defined as the need for respiratory support and/or oxygen for 28 days or more and at 36 weeks post-menstrual age. The need for oxygen is subjective and hence oxygen dependency will be confirmed using an ?oxygen reduction test?. This is based on whether the baby is able to maintain oxygen saturations over 90% for 1 hour whilst breathing air. Babies unable to achieve this will be considered to be oxygen dependant. _____ Previous primary outcome measures: Death or severe neuro-developmental disability at 2 years corrected age. The Bayley's scale of infant development III will be used to | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 03/08/2023: Short-term outcomes: 1. Death by 36 weeks postmenstrual age 2. Moderate or severe BPD at 36 weeks postmenstrual age 3. Severity of BPD at 36 weeks postmenstrual age 4. Incidence or duration of the following up to discharge: 4.1. Severe intraventricular haemorrhage (IVH) (grade III/IV with ventricular dilatation or intraparenchymal abnormality) 4.2. Cystic periventricular leukomalacia (PVL) 4.3. Non-cystic PVL 4.4. Hydrocephalus 4.5. Babies treated for retinopathy of prematurity (ROP) 4.6. Significant pulmonary haemorrhage (fresh blood in endotracheal tube with increase in respiratory support) 4.7. Treated for pulmonary hypertension with pulmonary vasodilator 4.8. NEC definitive and/or complicated (Bell stage II and above) confirmed by radiology and/or histopathology 4.9. NEC requiring surgery 4.10. Gastrointestinal bleeding (leading to investigation or clinical treatment) within 7 days of the first dose of trial drug administration 4.11. Spontaneous intestinal perforation 4.12. Closed or non-significant PDA (<1.5mm) at around 3 weeks of age (range of 18–24 days), confirmed by ECHO 4.13. PDA =1.5mm at around 3 weeks of age (range of 18–24 days) 4.14. Medical open-label treatment of a symptomatic PDA with a COX inhibitor 4.15. Open-label treatment of a symptomatic PDA by surgical treatment 4.16. Administration and duration of inotropic support 4.17. Total duration of respiratory support: 4.17.1. Invasive ventilation through an endotracheal tube 4.17.2. Non-invasive support through nasal CPAP, nasal ventilation, humidified high-flow nasal cannula therapy, or low-flow oxygen =1.1L/min 4.18. Discharge home on oxygen 4.19. Duration of initial hospitalisation (birth to discharge home) 4.20. Postnatal steroid use for chronic lung disease 4.21. Tolerance of ibuprofen treatment within the foreseeable SAE reporting range 4.22. Weight gain: a change in z score between birth and discharge (or death if sooner) 4.23. Head circum | — |
Countries
England, United Kingdom
Outcome results
None listed