E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemodynamically significant persisting ductus arteriosus in preterm infants of less than 28 weeks of gestational age |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034130 |
E.1.2 | Term | Patent ductus arteriosus |
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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 |
To determine whether the administration of Pedea® (intravenous ibuprofen) starting between 12 and 72 hours of life at a dose regimen of 20-10-10 mg/kg is safe and well tolerated in a population of preterm newborn infants of less than 28 weeks of GA treated for a hemodynamically significant PDA. |
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E.2.2 | Secondary objectives of the trial |
To determine at serial time points:
1 Plasma concentrations of ibuprofen enantiomers; 2 Plasma concentrations of total and unbound unconjugated bilirubin;
To evaluate the global PDA closure rate after treatment course.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Infants fulfilling the following criteria will be selected for participation in the study: - Written parental informed consents - Gestational age less than 28 weeks of amenorrhoea (up to 27 6/7 weeks) - Neonates aged minimum 12 hours of life and maximum 72 hours of life - Dependent on mechanical or non-invasive ventilation - Carrying a venous umbilical catheter - Presenting with an Hs PDA, defined as the evidence of a blood flow through the ductus arteriosus (left-to-right shunt) and/or of retrograde blood flow in the main pulmonary artery with colour Doppler and/or pulse Doppler with at least one of the following: o Ductus diameter > 1.5 mm/kg BW or o Left Atrium /Aortic root ratio > 1.4 or o Left-right shunt with low velocity (< 1 m/s) through the ductus arteriosus
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E.4 | Principal exclusion criteria |
Neonates presenting with one of the following criteria will not be included in the study: - Ductus-dependent cardiopathy - Right-to-left shunt over a persisting ductus arteriosus - Hydrops fetalis - Severe intra-ventricular haemorrhage (Papile’s grade 3 or 4) - Neurological functional disorders: seizures, coma - Life threatening infection - Thrombocytopenia < 30000/mm3 - Necrotising enterocolitis - Severe uncontrolled hyperbilirubinemia (TB > 171 µmol/L or 10 mg/dL) - Hepatocellular disease, hepatic insufficiency and/or hypoalbuminemia < mean reference value - 1 SD for the corrected gestational age (Reading RF, et al 1990) - Urine output below 1 mL per kilogram of birth weight per hour during the last 12 hours - Plasma creatinine concentration ≥ 140 µmol/L |
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E.5 End points |
E.5.1 | Primary end point(s) |
- An echocardiography will be performed to assess the status of the ductus 72 hours after the start of the first dose of ibuprofen. - Closure of the PDA will be defined by the absence of blood flow through the ductus and of retrograde flow in the pulmonary trunk, as evidenced by color and pulsed-wave Doppler. - The size (diameter) of the ductus arteriosus will be documented if it remains patent.
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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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
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.8.4.1 | 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 | Information not present in EudraCT |
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
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |