Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved]
A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a dr...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
F1000 Research Ltd
2020-11-01
|
| Series: | HRB Open Research |
| Online Access: | https://hrbopenresearch.org/articles/3-87/v1 |
| _version_ | 1818908598378430464 |
|---|---|
| author | Afif EL-Khuffash Neidin Bussmann Colm R. Breatnach Aisling Smith Elizabeth Tully Joanna Griffin Naomi McCallion John David Corcoran Elena Fernandez Claudia Looi Brian Cleary Orla Franklin Patrick J. McNamara |
| author_facet | Afif EL-Khuffash Neidin Bussmann Colm R. Breatnach Aisling Smith Elizabeth Tully Joanna Griffin Naomi McCallion John David Corcoran Elena Fernandez Claudia Looi Brian Cleary Orla Franklin Patrick J. McNamara |
| author_sort | Afif EL-Khuffash |
| collection | DOAJ |
| description | A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment. Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study’s purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years. Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015). |
| first_indexed | 2024-12-19T22:13:34Z |
| format | Article |
| id | doaj.art-3f2a640d41ac4c6dbcbf455e29f95d56 |
| institution | Directory Open Access Journal |
| issn | 2515-4826 |
| language | English |
| last_indexed | 2024-12-19T22:13:34Z |
| publishDate | 2020-11-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | HRB Open Research |
| spelling | doaj.art-3f2a640d41ac4c6dbcbf455e29f95d562022-12-21T20:03:50ZengF1000 Research LtdHRB Open Research2515-48262020-11-01310.12688/hrbopenres.13140.114253Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved]Afif EL-Khuffash0Neidin Bussmann1Colm R. Breatnach2Aisling Smith3Elizabeth Tully4Joanna Griffin5Naomi McCallion6John David Corcoran7Elena Fernandez8Claudia Looi9Brian Cleary10Orla Franklin11Patrick J. McNamara12Department of Neonatology, Rotunda Hospital, Dublin, IrelandDepartment of Neonatology, Rotunda Hospital, Dublin, IrelandDepartment of Neonatology, Rotunda Hospital, Dublin, IrelandDepartment of Neonatology, Rotunda Hospital, Dublin, IrelandDepartment of Obstetrics & Gynaecology, Royal College of Surgeons in Ireland, Dublin, IrelandDepartment of Research & Academic Affairs, Rotunda Hospital, Dublin, IrelandDepartment of Neonatology, Rotunda Hospital, Dublin, IrelandDepartment of Neonatology, Rotunda Hospital, Dublin, IrelandDepartment of Pharmacy, Rotunda Hospital, Dublin, IrelandDepartment of Pharmacy, Rotunda Hospital, Dublin, IrelandDepartment of Pharmacy, Rotunda Hospital, Dublin, IrelandDepartment of Paediatric Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin, IrelandDivision of Neonatology, Stead Family Children’s Hospital Stead Family Children’s Hospital, Iowa, USAA patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment. Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study’s purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years. Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015).https://hrbopenresearch.org/articles/3-87/v1 |
| spellingShingle | Afif EL-Khuffash Neidin Bussmann Colm R. Breatnach Aisling Smith Elizabeth Tully Joanna Griffin Naomi McCallion John David Corcoran Elena Fernandez Claudia Looi Brian Cleary Orla Franklin Patrick J. McNamara Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved] HRB Open Research |
| title | Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved] |
| title_full | Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved] |
| title_fullStr | Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved] |
| title_full_unstemmed | Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved] |
| title_short | Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT) [version 1; peer review: 2 approved] |
| title_sort | early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score study protocol for a randomised controlled trial pda rct version 1 peer review 2 approved |
| url | https://hrbopenresearch.org/articles/3-87/v1 |
| work_keys_str_mv | AT afifelkhuffash earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT neidinbussmann earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT colmrbreatnach earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT aislingsmith earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT elizabethtully earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT joannagriffin earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT naomimccallion earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT johndavidcorcoran earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT elenafernandez earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT claudialooi earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT briancleary earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT orlafranklin earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved AT patrickjmcnamara earlytargetedpatentductusarteriosustreatmentinprematureneonatesusingariskbasedseverityscorestudyprotocolforarandomisedcontrolledtrialpdarctversion1peerreview2approved |