The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia
| Autor: | Cochius-den Otter, Suzan, Schaible, Thomas, Greenough, Anne, van Heijst, Arno, Patel, Neil, Allegaert, Karel, van Rosmalen, Joost, Tibboel, Dick, Kipfmueller, Florian, Dolores Elorza, Maria, Sanchez, Ana, Martinez, Leopoldo, Labrandero, Carlos, Arreo, Viviana, Cortada, Pertierra, Clotet Caba, Jordi, Aguar, Marta, Gimeno, Ana, Escrig, Raquel, Capolupo, Irma, Bagolan, Pietro, Ciralli, Fabrizio, Raffaeli, Genny, Cavallaro, Giacomo, Condo, Valentina, Losty, Paul D, Horan, Marie, Subhedar, Nimish V, Singh, Yogen, Williams, Emma E, Dassios, Theodore, Bhat, Ravindra, Brandt, Jennifer B, Kreissl, Alexandra, Berger, Angelika, Urlesberger, Berndt, Burgos, Carmen Mesas, Frenckner, Bjorn, Larrson, Bjorn, Pinto, Carla, Saldaha, Joana, Debeer, Anne, Smits, Anne, Emblem, Ragnhild, Keijzer, Richard, Elsayed, Yassar, Tingay, David, Kraemer, Ulrike, Consortium, CDHEURO |
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| Přispěvatelé: | Pediatric Surgery, Epidemiology |
| Rok vydání: | 2019 |
| Předmět: |
Sildenafil
Hypertension Pulmonary Vasodilator Agents sildenafil Nitric Oxide Loading dose Sildenafil Citrate congenital diaphragmatic hernia Nitric oxide law.invention Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial Informed consent law nitric oxide Administration Inhalation pulmonary hypertension Protocol therapeutics Humans Medicine 030212 general & internal medicine Randomized Controlled Trials as Topic business.industry Infant Newborn Congenital diaphragmatic hernia Paediatrics General Medicine medicine.disease Pulmonary hypertension Diaphragm (structural system) chemistry Anesthesia Administration Intravenous Hernias Diaphragmatic Congenital business 030217 neurology & neurosurgery |
| Zdroj: | BMJ Open, 9, e032122 BMJ OPEN BMJ Open, 9, 11, pp. e032122 BMJ Open r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname BMJ Open, 9(11):e032122. BMJ Publishing Group |
| ISSN: | 2044-6055 |
| Popis: | IntroductionCongenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on ‘trial and error’. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.Methods and analysisIn an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018–2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) Ethics and disseminationEthics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained.Trial registration numberNTR6982; Pre-results. |
| Databáze: | OpenAIRE |
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