E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Preterm infants aged 30 weeks or less, who need resuscitation / stabilization maneuvers with positive pressure ventilation immediately after birth |
Recién nacidos prematuros de 30 semanas o menos, que necesitan reanimación / estabilización con maniobras de ventilación con presión positiva inmediatamente después de nacer |
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E.1.1.1 | Medical condition in easily understood language |
Preterm infants aged 30 weeks or less, who need ventilation for resuscitation immediately after birth. |
Recién nacidos prematuros de 30 semanas o menos, que necesitan reanimación con ventilación inmediatamente después de nacer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 investigate whether intervention consisting in lowering the initial inspiratory fraction of oxygen to 21% as compared to 60% in depressed extremely low gestational age neonates enhances survival without bronchopulmonary dysplasia (need for oxygen supplementation at 36 weeks corrected age). |
Investigar si la intervención consiste en la reducción de la fracción inspiratoria de oxígeno inicial al 21% en comparación con el 60% de los recién nacidos deprimidos de edad gestacional extremadamente baja, potencia la supervivencia sin displasia broncopulmonar (necesidad de oxígeno suplementario a las 36 semanas de edad corregida). |
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E.2.2 | Secondary objectives of the trial |
* Survival with reduced incidence of oxidative stress derived conditions: (i) retinopathy of prematurity (ROP) (ii) persistent ductus arteriosus (PDA) (iii) intra-periventricular hemorrhage and/or leukomalacia (IPVH/LM) (iv) necrotizing enterocolitis (NEC)
* Improving neurological outcome measured using the complete Bayley III scale (motor and psychological development) at 24 months postnatal.
* Reducing oxidative stress, oxidative damage to cell components and inflammation, DNA repair mechanisms as measured by specific biomarkers in the early postnatal period (<7 days postnatal). |
* La supervivencia con una menor incidencia de las condiciones de estrés oxidativo derivado: (i) la retinopatía del prematuro (ROP) (ii) la persistencia de conducto arterioso (PDA) (iii) intra-periventricular hemorragia y / o periventricular (IPVH / LM) (iv) la enterocolitis necrotizante (NEC)
* Mejoría en las variables neurológicas medidas utilizando la escala de Bayley III completa (motor y el desarrollo psicológico) a los 24 meses después del parto.
* Reducción del estrés oxidativo, daño oxidativo a los componentes de la célula y la inflamación, los mecanismos de reparación del ADN medidos por marcadores biológicos específicos en el período postnatal temprano (<7 días después del parto |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Preterm infants with gestational age of 30 weeks or less gestation born in tertiary referral centers and needing resuscitation/stabilization maneuvers with positive pressure ventilation immediately after birth |
Recién nacidos prematuros con edad gestacional de 30 semanas de gestación, o menos, nacidos en centros de tercer nivel y que necesitan reanimación / estabilización de las maniobras de ventilación con presión positiva inmediatamente después del nacimiento |
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E.4 | Principal exclusion criteria |
Uncertainty about gestational age Refusal to participate (parents/guardian) Not fulfilling study protocol Decoding in the delivery room Chromosomopaties Major malformations |
Incertidumbre acerca de la edad gestacional ? La negativa a participar (padres / tutores) El incumplimiento de protocolo de estudio Decodificación en la sala de partos Cromosomopatias Malformaciones graves. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Survival without bronchopulmonary dysplasia (need for oxygen supplementation at 36 weeks post-conceptional age) in preterm infants aged ? 30 weeks gestation. |
Supervivencia sin displasia broncopulmonar en neonatos de 30 semanas de gestación o menos |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After birth and at 36 weeks post conceptional age. |
Al nacer y tras 36 semanas de la edad gestacional. |
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E.5.2 | Secondary end point(s) |
* Survival with reduced incidence of oxidative stress derived conditions: (i) retinopathy of prematurity (ROP) grades 2 and 3 as defined by ETROP a. If in zone I: Stage 3 ROP, even without plus disease b. Plus disease with any stage ROP c. If in zone II: Plus disease with stage 2 ROP d. Plus disease with stage 3 ROP e. Any need for retinal surgery or the administration of avastin significant flow). (ii) intra-periventricular hemorrhage and/or leukomalacia (IPVH/LM) as detected by cranial ultrasonography (Papile LA et al J Pediatr 1983) (iii) necrotizing enterocolitis (NEC) (Bell?s classification Bell MJ Pediatr Clin N Amer 1985.
* Time of oxygen supplementation needed (days) * Time of mechanical ventilation needed including CPAP (days) * Doses of surfactant needed (n) * Incidence of air leaks (%) * Improved neurological outcome determined by Bayley III scale (motor and psychological development) at 24 months postnatal. * Reducing oxidative stress, oxidative damage to cell components and inflammation as measured by specific biomarkers in the early postnatal period (<7 days postnatal): (i) Reduced (GSH) and oxidized (GSSG) glutathione ratio (Mass Spectrometry) (ii) Interleukin 8 (ELISA) (iii) TNF? (ELISA) (iv) Ortho-tyrosine / Phenylalanine ratio (HPLC coupled to MS/MS) (v) 8-hydroxy-2-deoxyguanosine / 2 deoxyguanosine ratio (HPLC coupled to MS/MS) (vi) Isoprostanes and Isofurans (Gas chromatography coupled to MS/MS) (vii) Targeted and Untargetted metabolomics (viii) DNA repair mechanisms (ix) Proteomics |
* Supervivencia con incidencia reducida del estres oxidativo en las siguientes condiciones: (i) retinopatia del prematuro grados 2 y 3, definido por ETROP a. Si zona I: Estadio 3 ROP, incluso sin enfermedad extra b. Enfermedad adicional en cualquier estadio ROP c. Si zona II: Enfermedad adicional con estadio 2 ROP d. Enfermedad adicional con estadio 3 ROP e. Cualquier necesidad de cirugía retinal o de administracion de avastin (ii) hemorragia intraperiventricular y/o leucomalacia (IPVH/LM) detectada por ultrasonografia cranial (iii) enterocolitis necrotizante (NEC)
* Duracion necesidad de suplementacion con oxigeno (dias) * Duracion necesidad ventilacion mecanica incluyendo CPAP (Dias) * Dosis de surfactante necesario (n) * Incidencia perdidas aire (%) * Mejoria variable neurologica determinada por la escala Bayley III a los 24 meses del nacimiento * Reduccion del estres oxidativo, del daño oxidativo a los componentes celulares y de la inflamacion, medida a traves de biomarcadores especificos del periodo postnatal temprano (<7 dias): (i) Reduccion tasa GSH/GSSG (E.masas) (ii) Interleucina 8 (ELISA) (iii) TNF? (ELISA) (iv) Tasa ortotirosina/fenilalanina (HPLC acoplada a MS/MS) (v) Tasa 8-OH-2-deoxiguanosina/2-deoxiguanosina (HPLC acoplada a MS/MS) (vi) Isoprostanos e isofuranos (Cromatografia gases acoplada a MS/MS) (vii) Metabolitos diana y no diana (viii) Mecanismos reparacion ADN (ix) Proteonomica |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See above (E.5.2) |
Ver arriba (E.5.2) |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Mismo MI a diferente concentración/proporción |
Same IMP at a different concentration/proportion |
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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 | 2 |
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 | Yes |
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
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The end of trial will coincide with the follow up visit at 24months of age.
The End of Study Visit Form should include:Assessment of endpoints/outcome measures |
El final del ensayo coincidirá con la visita de seguimiento a 24 meses de edad.
El formulario de visita de fin de estudio debería incluir: evaluación de las variables de estudio. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |