E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
treatment of at term or late preterm newborn infants with severe respiratory disorders and pulmonary hypertension |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037400 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The study primary aim is to assess whether the use of sildenafil in term or late preterm (≥34 weeks) neonates with severe hypoxemia associated with persistent pulmonary hypertension (PH) improves oxygenation and decreases right ventricular pressure without increasing the incidence of side effects such as systemic arterial hypotension. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective are: in-hospital mortality and incidence of long-term outcomes (neurosensorial, auxological and respiratory impairments) not higher than those observed without the administration of sildenafil or following the use of iNO. The evaluation of some process indicators will be also performed, such as duration of mechanical ventilation, frequency of administration and dosage of inotropic drugs, amount and duration of iNO if used, hospitalization lenght. We expect these indicators to be reduced in sildenafil-treated infants, compared to non-treated ones. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
neonates ≥34 weeks of gestational age hospitalized in neonatal intensive care units (NICU) within the first week of life with acute respiratory failure of any origin, who require mechanical ventilation, either conventional (tidal) or high frequency oscillatory (HFOV), with an OI ≥10 and echocardiographic evidence of PH. |
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E.4 | Principal exclusion criteria |
major malformation, genetic/chromosomic anomalies incompatible with life or with increased risk of unfavorable neurological outcome, systemic hypotension (mean arterial blood pressure <2 SD the average value for birth weight [8], intracranial hemorrhage, previous iNO exposure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
a) ≥10 units OI reduction after treatment onset. OI will be determined at inclusion (time point 0), then every 6 hours, within 30 from the following S/P dose (time points 1 to 7), then 6 hours after the last dose (time point 8), then, lastly, 24 hours after (time point 9), through arterial blood sampling for PaO2 measurement, mean airway pressure (MAP) and FiO2 readings. Considering a maximum of 0.5 mL per sample, the total amount of blood drawn will be 5 mL for each subject. b) PP reduction. PP will be evaluated by echocardiography through doppler tricuspid regurgitation flow velocity if present, or through intra-ventricular septum configuration (flattened or left-bowed septum). PP will be evaluated at time point 0, then every 24 hours for 3 measurements (thus, the last evaluation will be performed 24 hours after last S/P administration, and will match the last OI determination). c) Systemic arterial hypotension. Arterial blood pressure will be measured non-invasively and expressed in mm Hg; it will be recorded at time point 0, then every 2 hours until 24 hours after the last S/P dose, thus matching the last OI/PP determination. Arterial hypotension will be defined as a mean arterial blood pressure <2 SD the average value for birth weight [8]. d) Other potential side effects will be noted through routine cardio-respiratory monitoring and clinical observation, such as gastro-intestinal intolerance (abdominal distension, clear or bile-stained aspirates), decreased urine output, vasomotor skin reactions. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3 | Other | No |
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.8.5 | 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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |