E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Persistent ductus arteriosus haemodynamically significant |
Ductus arterioso persistente hemodinamicamente significativo |
|
E.1.1.1 | Medical condition in easily understood language |
Persistent ductus arteriosus haemodynamically significant |
Ductus arterioso persistente hemodinamicamente significativo |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of the standard treatment of PDA with ibuprofen versus paracetamol in closing the patent ductus arteriosus to determine its non-inferiority to ibuprofen. |
Comparar la eficacia del tratamiento estándar del PDA con ibuprofeno versus paracetamol en el cierre del ductus persistente para determinar su no inferioridad frente a ibuprofeno. |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the safety of both treatments by the rate of early and late complications. 2. Set the pharmacokinetics and pharmacodynamics of paracetamol in the neonatal period in infants with persistent ductus. 3. Study of biomarkers and polymorphisms in urine |
1. Comparar la seguridad de ambos tratamientos mediante la tasa de complicaciones tempranas y tardías. 2. Establecer la farmacocinética y farmacodinamia del paracetamol en el período neonatal en recién nacidos con ductus persistente. 3. Estudio de biomarcadores y polimorfismos en orina |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Informed consent signed by parents or legal representative. ? Gestational age ? 30 weeks. ? Postnatal age ? 2 weeks ? 1st episode of hemodynamically significant PDA diagnosed by ultrasound: 1. Continuous flow through DAP. 2. Retrograde diastolic flow in the descending aorta. 3. Strain the left atrium. (relationship left atrium / aorta (LA / AO)> 1.5). 4. Ductal diameter greater than 1.7 mm. 5. Relationship ductus / descending aorta diameter size greater than 0.5. ? Need for ventilatory support ? Born in participating hospitals or coming to them in the application of the treatment period |
? Consentimiento informado firmado por padres o representante legal. ? Edad gestacional ? 30 semanas. ? Edad postnatal ? 2 semanas ? 1º episodio de DAP hemodinámicamente significativo diagnosticado mediante ecografía: 1. Flujo continuo a través de DAP. 2. Flujo retrogrado diastólico en la aorta descendente. 3. Distensión de la aurícula izquierda. (relación aurícula izquierda/ aorta (LA/AO) > 1.5). 4. Diámetro ductal superior a 1.7 mm. 5. Relación tamaño ductus/diámetro aorta descendente superior a 0.5. ? Necesidad de soporte ventilatorio ? Nacidos en hospitales participantes o llegada a los mismos dentro del periodo de aplicación del tratamiento |
|
E.4 | Principal exclusion criteria |
- Gestational age> 30 weeks - Postnatal age> 2 weeks - Major congenital malformations. - Impending doom. - Chromosomopaties. - Refusal to participate and / or sign the informed consent. - Inability to randomization or scrambling wrong. - Participation in another clinical trial - Diuresis less than 1 ml / kg / h for 8 h prior to treatment - Greater than 1.8 mg / dl Creatinine - Platelets below 50,000 / uL - Active bleeding (tracheal, gastrointestinal and renal) - Intraventricular hemorrhage recently (48h) (grades 3-4) - Severe hyperbilirubinemia - Liver failure or severe coagulopathy - Active necrotizing enterocolitis or intestinal perforation - Septic shock |
- Edad gestacional >30 semanas - Edad postnatal > 2 semanas - Malformaciones congénitas mayores. - Muerte inminente. - Cromosomopatías. - Rechazo a participar y/o firmar el consentimiento informado. - Imposibilidad de aleatorización o aleatorización errónea. - Participación en otro ensayo clínico - Diuresis inferior a 1 ml/kg/h en las 8 h previas al tratamiento - Creatinina superior a 1,8 mg/dl - Plaquetas inferiores a 50.000/?L - Hemorragia activa (traqueal, digestiva o renal) - Hemorragia intraventricular reciente (48h) (grados 3-4) - Hiperbilirrubinemia grave - Coagulopatía severa o fallo hepático - Enterocolitis necrotizante activa o perforación intestinal - Shock séptico |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Non-inferiority incidence of PDA clousure (clousure rate 80%) |
No inferioridad en la tasa de cierre de DAP (tasa cierre 80%) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After a máximum of 6 doses of paracetamol |
Después de como máximo 6 dosis de paracetamol |
|
E.5.2 | Secondary end point(s) |
Security: 1. Incidence of early complications: oliguria, renal failure, necrotizing enterocolitis, intraventricular hemorrhage, hyperbilirubinemia, gastrointestinal bleeding or perforation. 2. Incidence of late complications: bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of the newborn, sepsis, death Pharmacokinetics: 1. Determination of plasma levels of paracetamol 2. Pharmacodynamics of paracetamol in the ductus. pharmacokinetic model 3. Relationship plasma levels effectively / adverse reactions Biomarkers and polymorphisms 1. Determination of biomarkers and polymorphisms in urine 2. Relationship disposal / drug metabolism |
Seguridad: 1. Incidencia de complicaciones tempranas: oliguria, fallo renal, enterocolitis necrosante, hemorragia intraventricular, hiperbilirrubinemia, sangrado o perforación gastrointestinal. 2. Incidencia de complicaciones tardías: displasia broncopulmonar, leucomalacia periventricular, enterocolitis necrotizante, retinopatía del neonato, sepsis, muerte Farmacocinética y farmacodinamia: 1. Determinación de los niveles plasmáticos de paracetamol 2. Farmacodinamia del paracetamol en el ductus. Modelo farmacocinético 3. Relación niveles plasmáticos con efectividad/reacciones adversas Biomarcadores y polimorfismos 1. Determinación de biomarcadores y polimorfismos en orina 2. Relación con eliminación/metabolización del fármaco |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Early complications: during treatment Late complications: until discharge |
Complicaciones precoces: durante el tratamiento Complicaciones tardías: hasta el alta hospitalaria |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |