E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Persistent pulmonary hypertension of the newborn (PPHN) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053592 |
E.1.2 | Term | Newborn persistent pulmonary hypertension |
|
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 |
Efficacy: determine the efficacy of iv sildenafil in near term and term newborns with PPHN or with hypoxic respiratory failure and at risk for PPHN. The primary measure of efficacy will be the reduced need for iNO and extracorporeal membrane oxygenation ECMO).
Safety: to assess the safety and tolerability of iv sildenafil in near term and term newborns with PPHN or with hypoxic respiratory failure and at risk of developing PPHN. |
|
E.2.2 | Secondary objectives of the trial |
Efficacy: To assess the efficacy of iv sildenafil as measured by: oxygenation index; time to receipt of standard therapy (iNO or ECMO), days on mechanical ventilation, differential saturation; P/F ratio (PaO2/FiO2).
Pharmacokinetics: To further characterize the PK of sildenafil in newborns that have PPHN or hypoxic respiratory failure and at risk of developing PPHN. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Evidence of signed and dated informed consent document indicating that a legally acceptable guardian has been informed of all pertinent aspects of the study. 2. ≤72 hours of age; and ≥34 weeks gestational age at screening. 3. PPHN or Hypoxic respiratory failure associated with: a. Idiopathic PPHN or b. Meconium aspiration syndrome or c. Sepsis or d. Pneumonia 4. Oxygenation Index (OI) >15 and <60 calculated using blood gases taken approximately 30 minutes apart prior to commencement of study drug infusion. 5. Screening echocardiogram to confirm presence of pulmonary hypertension, performed within 24 hours of admission to GOSH. |
|
E.4 | Principal exclusion criteria |
Patients presenting with any of the following must not be included in the study: 1. Patients already receiving inhaled nitric oxide (iNO) on referral. 2. Prior or immediate need for full Cardio Pulmonary Resuscitation or Extracorporeal Membrane Oxygenation (ECMO). 3. Life threatening or lethal congenital anomaly. 4. Large left to right intracardiac or ductal shunting (diagnosed from echocardiogram on admission to GOSH). 5. Clinically significant active seizures as per clinical judgment. 6. Bleeding diathesis as per clinical judgment. 7. Participation in any other experimental studies before the current study begins or during the study participation. 8. Receipt of any prohibited concurrent medication/therapy at any time prior to screening: a. Potent cytochrome P450 3A4 inhibitors (eg, erythromycin, ketoconazole, itraconazole, and protease inhibitors). b. ritonavir or nicorandil. c. Endothelin antagonists (eg, Tracleer/bosentan). d. Nitrates or nitric oxide donors. A patient is eligible if nitroprusside was used only if it was discontinued at least 2 hours prior to study drug infusion; iNO may be used per protocol. e. Vasodilators (eg, alpha blockers, magnesium sulfate, calcium channel blockers, other PDE inhibitors, prostacyclins, etc). This excludes milrinone which is allowed during the study as concurrent therapy. f. Supplemental arginine administered for the purpose of improving NO-dependent vasodilation. Maintenance quantities in total parental nutrition (TPN) are allowed. 9. Known hereditary degenerative retinal disorders such as retinitis pigmentosa. 10. Symptoms of drug or alcohol related withdrawal. 11. In the opinion of the investigator, a patient who would be considered inappropriate for the study, for any reason: Other acute severe or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy - incidence of treatment failure: Need for an inhaled nitric oxide (iNO) or ECMO.
Safety: the following data will be used to assess the safety of iv sildenafil in this patient population: Incidence and severity of adverse events. Laboratory parameters. |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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
|
As defined in the protocol. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |