E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
to assess the impact of oral sildenafil administration on echocardiography measurements of pulmonary vascular resistance in neonates with Down Syndrome without Congenital Heart Disease. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067285 |
E.1.2 | Term | Vascular resistance pulmonary increased |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 |
The primary objective is to assess the impact of oral sildenafil administration on echocardiography measurements of pulmonary vascular resistance in neonates with Down Syndrome without Congenital Heart Disease. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the safety of sildenafil administration in this population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Antenatal or postnatal diagnosis of Down Syndrome in babies born from a singleton pregnancy at ≥35 weeks gestation. 2. Babies with a diagnosis of pulmonary hypertension, defined as two or more of the following echocardiography markers being present: (1) A PAAT < 40ms, (2) a PAAT:RVET < 0.25, (3) in the presence of a patent ductus arteriosus (PDA), the demonstration of bidirectional flow across the vessel or right to left flow; or (4) A left ventricular eccentricity index > 1.8. 3. Must live within 60 minutes by car or 50km of hospital
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E.4 | Principal exclusion criteria |
1. Lack of parental consent 2. Congenital heart disease other than a Patent Ductus Arteriosus 3. Other major congenital anomaly (such as gastrointestinal issues such as duodenal atresia, or renal or liver issues). 4. The presence of heart block or pre-excitation on a rhythm strip 5. Hypotension 6. Abnormal liver function tests at screening 7. Treatment with any of the following drugs: nitric oxide donors, nitrates, guanyl cyclase inhibitors (e.g. riociguat), potent CYP 3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir), alpha-blockers, vitamin K antagonists or bosentan. 8. History of a persistent bleeding disorder 9. Close family history of hereditary degenerative retinal disorders (such as retinitis pigmentosa) or sickle cell disease 10. Participation in another clinical trial of an investigational medicinal product within 30 days 11. Presence of any other illness or condition that renders the patient unsuitable for trial participation in the opinion of the investigator 12. Allergy or hypersensitivity to any of the components of Sildenafil 13. Any reason in the opinion of the investigator that the parent(s) would be unable to administer the investigational medicinal product to the subject
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome to be assessed is measurement of pulmonary vascular resistance using surrogate echocardiography markers performed at 2 months of age to include: • Pulmonary artery acceleration time indexed to heart rate • Left ventricular eccentricity index • Tricuspid regurgitant jet velocity (if present)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints all assessed at 2 months of age:
• Full blood count including platelet counts at 3 months of age • Full renal profile including urea and creatinine • Full liver profile • Incidence of hypotension • Incidence of arrhythmias
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Infants in the control arm will receive standard of care (no PVR lowering agent) |
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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 | 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 | 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 study assessment procedures are described above. The end of trial will be the date of the last visit of the last subject anticipated to be 2 years after enrolment of the first subject. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |