E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis E |
Hepatitis Crónica E |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis E |
Hepatitis Crónica E |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019768 |
E.1.2 | Term | Hepatitis E |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
Efficacy assessment (sustained virologic response rate) with Ribavirina in two therapeutic strategies with ribavirina in patients with chronic hepatitis E and severe acute. |
Valoración de la eficacia (tasa de respuesta virológica sostenida) del tratamiento con Ribavirina en dos estrategias terapéuticas con ribavirina en pacientes con hepatitis E crónica y aguda grave. |
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E.2.2 | Secondary objectives of the trial |
- To define the recidiva real rate of the chronic hepatitis by a prospective 12 months trial. - Validation of Fibroscan as diagnostic test for the fibrosis in the chronic hepatitis E. - Identification of risk factors associated with chronic hepatitis E ( type of immunosuppression , analytical data , epidemiological factors ... ) . - To reduce costs derived from the control of the symptomatic hemolytic anemia in patients under treatment by the adjustment of Ribavirina's plasmatic levels and hemoglobin. - Study of the possible mutagenic effect of ribavirin in patients with chronic hepatitis E. |
- Definir la verdadera tasa de recidiva de la hepatitis crónica E mediante un estudio prospectivo y con un seguimiento de 12 meses. - Validación de la Elastografía de transición (Fibroscan) como test diagnóstico de fibrosis en la hepatitis crónica E. - Identificación de factores de riesgo asociados a la hepatitis crónica E (tipo de inmunosupresión, datos analíticos, factores epidemiológicos?). - Reducir los costes derivados del control de la anemia hemolítica sintomática en pacientes bajo tratamiento por medio del ajuste de dosis a niveles plasmáticos de Ribavirina y hemoglobina. - Estudio del posible efecto mutagénico de la Ribavirina en los pacientes con hepatitis crónica E. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 18 years old or above. - That meet one of the following two diagnostics: a) chronic Hepatitis E: HEV RNA detectable in patients with elevated transaminase levels for at least 6 months and / or HEV RNA detectable in two separated by an interval of six months determinations. b) Severe acute hepatitis E: ALT levels greater than 10 times the normal limit , HEV RNA positive , and signs of acute liver injury (INR > 1.5) ; or extrahepatic manifestations or liver failure in patients with previous liver disease. - Signed informed consent |
- Edad igual o superior a 18 años. - Que cumplan alguno de los siguientes dos diagnósticos: a) Hepatitis crónica E: RNA VHE detectable en pacientes con elevación de los niveles de transaminasas durante al menos 6 meses y/o RNA VHE detectable en 2 determinaciones separadas por un intervalo de 6 meses. b) Hepatitis aguda grave E: niveles de ALT superior a 10 veces el límite de la normalidad, con RNA VHE positivo, y signos de lesión hepática aguda (INR> 1.5); o con manifestaciones extrahepáticas o fallo hepático en pacientes con hepatopatía previa. - Firma del consentimiento informado |
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E.4 | Principal exclusion criteria |
- Terminal illness with a life expectancy of less than six months. - Patients with contraindications for treatment with Ribavirin : a) Pregnancy or breastfeeding b) Hepatic serious insufficiency or unbalanced cirrhosis. c) Hemoglobinopathies ( thalassemia , sickle cell anemia ) . d) History of severe pre-existing cardiac disease , including unstable heart disease . |
- Enfermedad terminal, con una esperanza de vida esperada inferior a 6 meses. - Pacientes con contraindicación para el tratamiento con Ribavirina: a) Gestación o lactancia. b) Insuficiencia hepática grave o cirrosis descompensada. c) Hemoglobinopatías (Talasemia, anemia de células falciformes). d) Antecedente de Enfermedad cardíaca grave preexistente, incluida cardiopatía inestable. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sustained virological response ( HEV RNA undetectable at 48 weeks after completion of treatment ) . |
Respuesta virológica sostenida (RNA VHE indetectable a las 48 semanas de haber finalizado el tratamiento). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 48 weeks after treatment ends . |
A las 48 semanas de haber finalizado el tratamiento. |
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E.5.2 | Secondary end point(s) |
- Virological response at the end of treatment ( RNA undetectable at end of treatment with ribavirin HEV) . - Ribavirin dose titration according to drug plasma levels. Ribavirin plasma levels of each patient were recorded every 4 weeks |
- Respuesta virológica al final de tratamiento (RNA VHE indetectable al final de tratamiento con ribavirina). - Ajuste de dosis ideal de ribavirina según niveles plasmáticos de fármacos. Se registrarán los niveles plasmáticos de ribavirina de cada paciente cada 4 semanas |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 12 or 24 weeks depending on the group . - Every 4 weeks |
- A las 48 semanas de haber finalizado el tratamiento. - Cada 4 semanas. |
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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 | 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 | Yes |
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 |
2 regimenes de ribavirina |
2 ribavirin regimens |
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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 | 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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |