E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cardiac failure, ascites and/or oedema |
südamepuudulikkus, tursed, astsiit |
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E.1.1.1 | Medical condition in easily understood language |
cardiac failure, ascites and/or oedema |
südamepuudulikkus, tursed, astsiit |
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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 | 17.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10010394 |
E.1.2 | Term | Congenital cardiac disorders |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049630 |
E.1.2 | Term | Oedema due to renal disease |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030103 |
E.1.2 | Term | Oedema generalized |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003445 |
E.1.2 | Term | Ascites |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
Aims of the study
- To describe PK profile of spironolactone in children up to two years of age with cardiac failure, ascites and/or oedema
- To describe PK parameters of the main metabolites of spironolactone (7 alpha- thiomethylspironolactone and canrenone) in children up to two years of age
- To correlate plasma PK profiles of spironolactone with predefined clinical efficacy measures in children up to two years of age with cardiac failure, ascites and/or oedema
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E.2.2 | Secondary objectives of the trial |
• To describe PK profile of spironolactone in children up to two years of age with cardiac failure, ascites and/or oedema;
• To describe PK parameters of the main metabolites of spironolactone (7 alpha- thiomethylspironolactone and canrenone) in children up to two years of age;
• To correlate plasma PK profiles of spironolactone with predefined clinical efficacy measures in children up to two years of age with cardiac failure, ascites and/or oedema;
• To assess the safety profiles of oral spironolactone in children up to two years of age.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
1. Age 35+0 weeks of gestation up to two years of age
2. Clinical need for spironolactone treatment due to heart failure, ascites, oedema
3. Clinical need for an arterial, central venous or venous catheter
4. Admission to study units
5. Informed consent by the parents or by the legitimate representative of the child.
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E.4 | Principal exclusion criteria |
1. Acute renal insufficiency, oligoanuria
diuresis <0.5 ml/kg/h; creatinine >100 mcmol/L
2. Addison's disease or other conditions associated with hyperkalemia
3. Hyperkalemia >5.5 mmol/l
4. Hyponatraemia <130.0 mmol/l
5. Hypersensitivity to spironolactone
6. Concomitant use of potassium sparing diuretics
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E.5 End points |
E.5.1 | Primary end point(s) |
• A noncompartmental model of disposition of spironolactone and its main metabolites
o CL, Vd, AUC, Cmax, Tmax
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• A noncompartmental model of disposition of spironolactone and its main metabolites
o CL, Vd, AUC, Cmax, Tmax |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood samples for spironolactone and main metabolites plasma concentration measurements will be collected before and in the following time-points after the study dose of the drug: 30 min, 60 min, 1,5h, 4h, 8h, 12h, 23h and also 46h and 72h after study dose if feasible or from the leftovers of regular blood analyses drawn after the 23 hour post dose. |
Blood samples for spironolactone and main metabolites plasma concentration measurements will be collected before and in the following time-points after the study dose of the drug: 30 min, 60 min, 1,5h, 4h, 8h, 12h, 23h and also 46h and 72h after study dose if feasible or from the leftovers of regular blood analyses drawn after the 23 hour post dose. |
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E.5.2 | Secondary end point(s) |
NA |
Safety endpoints
Specific safety end-points will not be applied as the treatment is clinically indicated and routinely used in this specific clinical setting. However, all participating patients will be subjects of multiparametric monitoring and all adverse effects will be recorded and documented during study period and 7 days thereafter (for details please see below and CRF).
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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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7 days after study dose administration. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |