E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory convulsive status epilepticus, defined as the recurrence of crisis for more than 60 minutes and / or drug-resistant I l and II line. |
Stato di male epilettico convulsivo refrattario, definito come il ripetersi di crisi per oltre 60 minuti e/o resistente ai farmaci di I e II linea. |
|
E.1.1.1 | Medical condition in easily understood language |
Refractory convulsive status epilepticus, defined as the recurrence of crisis for more than 60 minutes and / or drug-resistant I and II line. |
Stato di male epilettico convulsivo refrattario, definito come il ripetersi di crisi per oltre 60 minuti e/o resistente ai farmaci di I e II linea. |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057955 |
E.1.2 | Term | Convulsive status epilepticus |
E.1.2 | System Organ Class | 100000004852 |
|
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 evaluate the efficacy of intravenous administration of KE in the treatment of refractory convulsive status epilepticus compared to administration of MDZ at high doses (TPS and / or PR). |
Valutare l'efficacia della somministrazione per via endovenosa della KE nel trattamento dello stato di male epilettico convulsivo refrattario rispetto alla somministrazione di MDZ ad alte dosi e (TPS e/o PR). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of intravenous administration of KE in the treatment of refractory convulsive status epilepticus compared to administration of MDZ at high doses (TPS and / or PR). |
Valutare l'efficacia della somministrazione per via endovenosa della KE nel trattamento dello stato di male epilettico convulsivo refrattario rispetto alla somministrazione di MDZ ad alte dosi e (TPS e/o PR). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients 1 month to 18 years old. 2) Diagnosis and clinical EEGrafica of refractory convulsive status epilepticus 3) Refractoriness of the drug I and II line 4) Written informed consent from parents or legal guardian. 5) Administration of rating scales in the risk of mortality (PIM III) and severity of SE (stess, status epilepticusseverity score) to be performed prior to randomization. |
1) Pazienti da 1 mese a 18 anni di età. 2) Diagnosi clinico-EEGrafica di stato di male epilettico convulsivo refrattario 3) Refrattarietà ai farmaci di I e II linea 4) Consenso informato scritto da parte dei genitori o tutore legale. 5) Somministrazione di scale di valutazione del rischio di mortalità (PIM III) e di gravità dello SE (STESS, status epilepticusseverity score) da eseguire prima della randomizzazione.
|
|
E.4 | Principal exclusion criteria |
1) contraindications to the use of the medication/s in the study. 2) pregnant or suspected pregnant. |
1) controindicazioni all'uso del/i farmaco/i in studio. 2) stato di gravidanza presunta o accertata. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Resolution of refractory convulsive status epilepticus |
Risoluzione dello stato di male epilettico convulsivo refrattario |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) Frequency of electro-medical crisis during treatment; 2) Frequency of crisis from outcome at hospital discharge; 3) Proportion of patients requiring intubation during treatment with KE; 4) Proportion of patients for whom it is necessary to support the use of cardiovascular drugs (amine) for heart failure secondary to ongoing therapy; 5) Proportion of subjects who respond to alternative therapy given after the registration of a therapeutic failure in the arm allocation; 6) Proportion of patients requiring discontinuation of study treatment for adverse events; 7) Proportion of treatment failures due to death (within 24 hours after discontinuation of therapy); 8) in-hospital mortality; 9) time to assisted ventilation |
1) Frequenza delle crisi elettro-cliniche durante il trattamento a partire dal raggiungimento della dose massima dei farmaci in studio fino all’accertamento dell’outcome; 2) Frequenza delle crisi dall’accertamento dell’outcome alla dimissione dall’ospedale; 3) Proporzione di pazienti richiedenti intubazione in corso di trattamento con KE; 4) Proporzione di pazienti per i quali si rende necessario il ricorso a farmaci di supporto cardiovascolare (amine) per scompensi secondari alla terapia in corso; 5) Proporzione di soggetti che rispondono alla terapia alternativa somministrata dopo la registrazione di un insuccesso terapeutico nel braccio di allocazione; 6) Proporzione di pazienti che richiedono l’interruzione del trattamento in studio per comparsa di eventi avversi; 7) Proporzione di insuccessi terapeutici per decesso (entro le 24 ore dalla sospensione della terapia); 8) Mortalità intraospedaliera; 9) Durata del tempo di ventilazione assistita
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Multicentrico e sequenziale con test triangolare |
Multicenter and sequential triangular test |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 9 |
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
|
Resolution of refractory convulsive status epilepticus |
Risoluzione dello stato di male epilettico convulsivo refrattario |
|
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 | |
E.8.9.1 | In the Member State concerned days | |