E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild-moderate symptomatic hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) |
IPONATREMIA LIEVE-MODERATA SINTOMATICA SECONDARIA A SINDROME DA INAPPROPRIATA SECREZIONE DI ORMONE ANTIDIURETICO (SIADH) |
|
E.1.1.1 | Medical condition in easily understood language |
Mild-moderate symptomatic hyponatremia due to inappropriate secretion of antidiuretic hormone |
IPONATREMIA LIEVE-MODERATA SINTOMATICA SECONDARIA AD INAPPROPRIATA SECREZIONE DI ORMONE ANTIDIURETICO |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10014698 |
E.1.2 | Term | Endocrine disorders |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
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 |
Evaluation of effectiveness and safety of Tolvaptan in the treatment of mild-moderate symptomatic hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients who underwent transsphenoidal surgery for hypothalamic-pituitary disorders. |
Valutazione dell’efficacia e della sicurezza di Tolvaptan nel trattamento dell’iponatremia lieve-moderata post-chirurgica da sindrome da inappropriata secrezione di ormone antidiuretico in pazienti operati per patologie della regione ipotalamo-ipofisaria |
|
E.2.2 | Secondary objectives of the trial |
Evaluation of mean resolution time of hyponatremia in the two groups of treatment (tolvaptan vs fluid resctriction). |
Valutazione del tempo medio di risoluzione dell’iponatremia nei due gruppi di trattamento (tolvaptan vs restrizione idrica). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age >18
- admission to Neurosurgery Unit for pituitary surgery
- Serum sodium levels lower than 135 mEq/l and higher than 120 mEq/l
- One or more symptoms of hyponatremia
- Euvolemic patient
- Informed consent |
• Età > 18 anni
• Ricovero c/o U.O. Neurochirurgia per intervento neurochirurgico di asportazione patologia sellare via transnasosfenoidale (TNS).
• Sodio serico < 135 mEq/L e > o uguale a 120 mEq/L
• Presenza di almeno 1 sintomo riferibile ad iponatremia
• Euvolemia
• Consenso informato |
|
E.4 | Principal exclusion criteria |
- Anuria
- Impaired renal function(grade IV KDOQI)
- Liver failure
- Hypovolemia
- Hyponatremic hypovolemia
- Lack of sense to thirst
- Cotreatment with inhibitors/inductors of CYP3A4
- Pregnancy
- Brestfeeding |
• Anuria
• Grave insufficienza renale (stadio IV secondo KDOQI)
• Grave insufficienza epatica (classe C di Child-Pugh)
• Deplezione volemica
• Iponatremia ipovolemica
• Pazienti non in grado di avvertire la sete
• Trattamento con farmaci inibitori o induttori di CYP3A4
• Gravidanza
• Allattamento |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Normalization of serum sodium levels in patients affected by sindrome of inappropriate secretion of antidiuretic hormone |
Normalizzazione dei livelli di sodio in pazienti affetti da iponatremia secondaria a sindrome da inappropriata secrezione di ormone antidiuretico |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Between 1 and 10 days |
Variabile, tra 1 e 10 giorni |
|
E.5.2 | Secondary end point(s) |
Reduction of mean resolution time of hyponatremia in patients reated with Tolvaptan in respect to patients treated with fluid restriction |
Riduzione del tempo di risoluzione dell'iponatremia in pazienti trattati con Tolvaptan rispetto a quelli trattati con restrizione idrica |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between 1 and 10 days |
Variabile, tra 1 e 10 giorni |
|
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 |
Restrizione idrica |
Fluid restriction |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |