| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| 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 |
To describe the potential alteration (in terms of benefit or impairment) of renal function during and after treatment with AAD in the context of the currently recommended treatment of chronic hepatitis C.
Change in renal function was defined as the change in glomerular filtration (established by the CDK-EPI equation) greater than ≥ 10 mL / min / 1.73 m2 or a change> 10% with respect to baseline glomerular filtration. |
Describir la potencial alteración (en términos de beneficio o deterioro) de la función renal durante y después del tratamiento con AAD en el contexto del tratamiento actualmente recomendado de la hepatitis crónica C.
Se define cambio en la función renal como la variación del filtrado glomerular (establecido mediante la ecuación CDK-EPI) mayor del ≥10 mL/min/1.73 m2 o un cambio >10% con respecto al filtrado glomerular basal. |
|
| E.2.2 | Secondary objectives of the trial |
1. Describe the proportion of patients with changes in renal function during and after completion of treatment with direct antivirals.
2. Evaluate changes in the tubular function of patients undergoing antiviral treatment. Change in tubular function is defined as the appearance of proteinuria or hematuria at any time during treatment administration.
3. Determine differences in acute renal failure and tubular damage between different treatments with rapid-acting antiviral agents.
4. Analyze if these alterations are maintained after the end of treatment and there is a tubular damage and renal function maintained over time.
5. Analyze the temporal profile of the alteration of the renal function and the reversibility of the same.
6. Describe the proportion of patients with glomerular filtration below 90 ml / min
7. Describe the proportion of patients with de novo tubular and glomerular alteration. |
1. Describir la proporción de pacientes con cambios en la función renal durante y tras la finalización del tratamiento con antivirales directos.
2. Evaluar los cambios en la función tubular de los pacientes sometidos a tratamiento antiviral. Se define cambio en la función tubular como la aparición de proteinuria o hematuria en cualquier momento durante la administración del tratamiento.
3. Determinar diferencias en fracaso renal agudo y daño tubular entre diferentes tratamientos con agentes antivirales de acción rápida.
4. Analizar si estas alteraciones se mantienen después de terminar el tratamiento y existe un daño tubular y de función renal mantenido en el tiempo.
5. Analizar el perfil temporal de la alteración de la función renal y la reversibilidad de la misma.
6. Describir la proporción de pacientes con filtrado glomerular inferior a 90 ml/min
7. Describir la proporción de pacientes con alteración tubular y glomerular de novo. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| SUBSTUDIO MONITORING OF ACUTE RENAL FUNCTION AND TUBULAR DAMAGE |
| SUBESTUDIO DE MONITORIZACIÓN DE LA FUNCIÓN RENAL DE FORMA AGUDA Y DEL DAÑO TUBULAR |
|
| E.3 | Principal inclusion criteria |
Patients with chronic HCV genotype see above, regardless of the degree of fibrosis, with sofosbuvir / ledipasvir or 3D regimen of Abvvie. Patients should NOT receive ribavirin in their therapeutic regimen.
Age greater than 18.
Baseline glomerular filtration greater than 30 ml / min.
Written informed consent in accordance with ICH / GCP and Spanish legislation obtained before any study procedure. |
- Pacientes con hepatitis crónica por VHC genotipo ver antes, independiente del grado de fibrosis, con sofosbuvir/ledipasvir o regimen 3D de Abvvie. Los pacientes NO deben recibir ribavirina en su esquema terapeútico.
- Edad superior a 18.
- Filtrado glomerular basal superior a 30 ml/min.
- Consentimiento informado escrito conforme a ICH/GCP y a la legislación española, obtenido antes de cualquier procedimiento de estudio. |
|
| E.4 | Principal exclusion criteria |
-Coinfection with VHD (hepatitis delta virus), HBV (hepatitis C virus) or HIV (human immunodeficiency virus).
- Fibroscan> 14
- Evidence of current or previous decompensation (ascites, HDA, encephalopathy).
- Diagnosis of CHC (Hepatocellular Carcinoma).
- Diagnosis of cryoglobulinemia
- Mellitus diabetes
- Intake of alcohol equal to or greater than 50 grams of alcohol.
- Patients undergoing liver transplantation.
- Patients with platelets <50,000, hemoglobin <10 g / dl, albumin <3 g / l, bilirubin> 2.5.
- Use of nephrotoxic agents.
- If in the opinion of the researcher there are findings in the physical examination, anomalies in the results of the clinical analyzes or other medical, social or psychosocial factors that could influence negatively.
- Have received any investigational drug within 60 days prior to study drug administration.
- Inability to give informed consent. |
- Coinfección con VHD (virus hepatitis delta), VHB (virus hepatitis C) o VIH (virus de inmunodeficiencia humana).
- Fibroscan > 14
- Evidencia de descompensación (ascitis, HDA, encefalopatía) actual o previa.
- Diagnóstico de CHC (Carcinoma Hepatocelular).
- Diagnostico de crioglobulinemia
- Diabetes mellitus
- Ingesta de alcohol igual o superior a 50 gramos de alcohol.
- Pacientes sometidos a trasplante hepático.
- Pacientes con plaquetas <50.000, hemoglobina <10 gr/dl, albúmina <3 gr/l, bilirrubina >2,5.
- Uso de agentes nefrotóxicos.
- Si en opinión del investigador existen hallazgos en la exploración física, anomalías en los resultados de los análisis clínicos u otros factores médicos, sociales o psicosociales que pudieran influir negativamente.
- Haber recibido cualquier fármaco en investigación en los 60 días anteriores a la administración del fármaco del estudio.
- Incapacidad para dar el consentimiento informado. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Glomerular filtration according to CKD-EPI |
| Filtrado glomerular según CKD-EPI |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Basal, end of treatment and 12 weeks posttreatment |
| Basal, fin de tatameinto y 12 semanas tras finalizar el tratamiento |
|
| E.5.2 | Secondary end point(s) |
1211/5000
Monitoring the reversibility of renal damage
• creatinine clearance
• Glomerular filtration,
• Total proteinuria,
• Presence of hematuria,
• Albumin / Creatinine ratio,
• Proteinuria / creatinine ratio
• β2 microglobulin / creatinine ratio
• Retinol binding protein
• Phosphorus / creatinine ratio
Monitoring of acute renal damage (kinetics)
• Cystatin C
• NGAL
• KIM-1
Efficacy of treatment
• Sustained viral response (SVR12): Undetectable HCV RNA (<50 IU / ml) 12 weeks after the end of treatment
• Viral response at week 4 after completion of treatment
• Viral response at the end of treatment, HCV RNA at the end of treatment.
• Viral response at treatment week 4; Rapid virological response. Undetectable HCV RNA (<50 IU / ml) at 4 weeks of initiation of treatment
Security
• Physical examination: basic before and after the experiment.
• Vital signs
• Lab tests
• Clinical safety assessment. Adverse Events:
O Adverse effects (EA): listed by treatment, laboratory values, values outside the reference range and descriptive statistics.
O Adverse effects of special interest: Nephrotoxicity |
Monitorización de la reversibilidad de daño renal
• Aclaramiento de creatinina,
• Filtrado glomerular,
• Proteinuria total,
• Presencia de hematuria,
• Relación Albumina/Creatinina,
• Relación Proteinuria/creatinina
• Relación β2 microglobulina/creatinina
• Retinol binding protein
• Indice fosforo / creatinina
Monitorización del daño renal agudo (cinética)
• Cistatina C
• NGAL
• KIM-1
Eficacia del tratamiento
• Respuesta viral sostenida (RVS12): ARN del HCV indetectable (< 50 UI/ml) 12 semanas después del final del tratamiento
• Respuesta viral en semana 4 tras finalizar tratamiento
• Respuesta viral al finalizar el tratamiento, ARN del HCV al finalizar el tratamiento.
• Respuesta viral en semana 4 de tratamiento; respuesta virológica rápida. ARN del HCV indetectable (< 50 UI/ml) a las 4 semanas de iniciar el tratamiento
Seguridad
• Examen físico: básico antes y después del experimento.
• Signos vitales
• Pruebas de laboratorio
• Evaluación de la seguridad clínica. Acontecimientos adversos:
o Efectos adversos (EA): listado por tratamiento, valores de laboratorio, valores fuera del rango de referencia y estadísticas descriptivas.
o Efectos adversos de especial interés: Nefrotoxicidad |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Basal, weeks 2, 4, 8, end of treatment and 12 and 24 weeks posttreatment |
| Basal, semanas 2, 4, 8, final del tratamiento y 12 y 24 semanas después del tratamiento |
|
| 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 | Yes |
| E.6.5 | Efficacy | No |
| 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 | No |
| E.8.1.2 | Open | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 100 |
| 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
|
| End of follow-up of the last patient recruited |
| FIn de seguimiento del ultimo paciente reclutado |
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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 | |
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