E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with decompensated cirrhosis and ascites |
Sujetos con cirrosis descompensada y ascitis |
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E.1.1.1 | Medical condition in easily understood language |
Cirrhosis and ascites |
Cirrosis y ascitis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064704 |
E.1.2 | Term | Decompensated cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
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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 |
To evaluate the effect of standard medical treatment (SMT) plus long-term Albutein 20% (SMT + Albutein 20%) administration on 1-year transplant-free survival versus SMT alone. |
Evaluar el efecto del tratamiento médico estándar (TME) más la administración prolongada de Albutein 20% (TME + Albutein 20%) en la supervivencia libre de trasplante a 1 año versus el TME solo. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effects of SMT + Albutein 20% administration on 3- and 6-month transplant-free and overall survival versus SMT alone
- To evaluate the effects of SMT + Albutein 20% administration on 1-year overall survival versus SMT alone
- To evaluate the total number of paracenteses and the incidence of refractory ascites according the International Club of Ascites (ICA) criteria |
- Evaluar los efectos de la administración del TME + Albutein 20% a los 3 y 6 meses de supervivencia libre de trasplante y la supervivencia global versus el TME solo
- Evaluar los efectos de la administración del TME + Albutein 20% sobre la supervivencia global a 1 año versus el TME solo
- Evaluar el número total de paracentesis y la incidencia de ascitis refractaria según los criterios del Club Internacional de Ascitis (ICA) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subject ≥18 years of age. 2. Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology) and uncomplicated ascites according to the ICA criteria. 3. Subjects being discharged after hospitalization for acute decompensation of liver cirrhosis with ascites (or with prior history of ascites requiring diuretic therapy) with or without ACLF at admission or during hospitalization but without ACLF at discharge. 4. Subjects with ongoing diuretic treatment with an anti-mineralocorticoid drug at a dose of ≥100 mg/day and furosemide ≥40 mg/day independent of response to treatment. 5. In subjects with cirrhosis due to HBV, decompensation must occur in the setting of continuous (not <3 months) appropriate antiviral therapy. 6. In subjects with cirrhosis due to HCV, only decompensated patients who will not receive antiviral therapy during the study period will be included. 7. In subjects with cirrhosis due to autoimmune hepatitis, decompensation must occur in the setting of continuous immunosuppressive therapy. 8. Subjects must be willing and able to provide written informed consent or have an authorized representative able to provide written informed consent on behalf of the subject in accordance with local law and institutional policy. |
1. Hombres y mujeres ≥ 18 años de edad. 2. Diagnóstico de cirrosis hepática y ascitis no complicada (basado en datos clínicos, de laboratorio, endoscópicos y ultrasonográficos o en la histología) y ascitis no complicada de acuerdo con los criterios del ICA. 3. Sujetos dados de alta después de la hospitalización por descompensación hepática aguda con ascitis (o con previa historia de ascitis requiriendo terapia con diuréticos) con o sin ACLF en el ingreso o durante la hospitalización pero sin ACLF al alta. 4. Sujetos con tratamiento diurético en curso con antimineralocorticoides a la dosis de ≥100 mg/día y furosemida ≥40 mg/día independientemente de la respuesta del tratamiento. 5. Sujetos con cirrosis debida a hepatitis B, la descompensación debe ocurrir en el marco de una terapia antiviral continua (no <3 meses) apropiada. 6. Sujetos con cirrosis debida a la hepatitis C, sólo se incluirán pacientes descompensados que no recibirán terapia antiviral durante el período de estudio. 7. Sujetos con cirrosis debida a hepatitis autoinmune, la descompensación debe ocurrir en el establecimiento de terapia inmunosupresora continua. 8. Sujetos que quiera y puedan dar el consentimiento informado por escrito o tengan un representante legal capaz de dar el consentimiento informado por escrito en nombre del sujeto de acuerdo con las leyes locales y las políticas institucionales. |
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E.4 | Principal exclusion criteria |
1. Subjects with ongoing ACLF at discharge. 2. Subjects with ongoing or recent (within the last 30 days) HRS, infection, or bleeding complications. 3. Subjects with TIPS or other surgical porto-caval shunts. 4. Subject with an established diagnosis of refractory ascites as defined by ICA criteria. 5. Subjects requiring ≥2 paracenteses during the previous 30 days. 6. Subjects receiving anti-platelet therapy or anti-coagulant therapy during the previous 30 days. 7. Subjects with ongoing endoscopic eradication of esophageal varices at discharge. 8. Subjects with HE grade III or IV. 9. Subjects with evidence of current locally advanced or metastatic malignancy. Subjects with hepatocellular carcinoma within the Milan criteria [1 nodule ≤5 cm or 3 nodules ≤3 cm]], non-melanocytic skin cancer, or controlled breast or prostate cancer can be included. 10. Subjects with chronic heart failure (New York Heart Association [NYHA]). 11. Subjects with severe (grade III or IV) pulmonary disease (Global Obstructive Lung Disease [GOLD]). 12. Subjects with serum creatinine >2.0 × upper limit of normal ([ULN] based on local laboratory results obtained prior to discharge). 13. Subjects with organic nephropathy as defined by ICA criteria. 14. Subjects with severe psychiatric disorders. 15. Subjects with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection. 16. Females who are pregnant, breastfeeding, or, if of childbearing potential, unwilling to practice a highly effective method of contraception. 17. Subjects with previous liver transplantation. 18. Subjects with known or suspected hypersensitivity to albumin. 19. Subjects participating in another clinical study within 3 months prior to screening. 20. Subjects with active drug addiction. 21. In the opinion of the investigator, the subject may have compliance problems with the protocol and the procedures of the protocol. |
1. Sujetos con ACLF al ser dados de alta. 2. Sujetos con SHR, infección o complicaciones hemorrágicas en curso o recientes (30 días previos). 3. Sujetos con TIPS u otros shunts porto-caval quirúrgicos. 4. Sujetos con un diagnóstico establecido de ascitis refractaria según lo definido por los criterios del IAC. 5. Sujetos que requieren ≥ 2 paracentesis durante los últimos 30 días. 6. Sujetos en terapia plaquetaria o anticoagulante durante los 30 días previos. 7. Sujetos con erradicación endoscópica de varices esofágicas en curso al alta. 8. Sujetos con grado III / IV de encefalopatía hepática. 9. Sujetos con evidencia de neoplasias localmente avanzadas o malignidades metastáticas. Sujetos con carcinoma hepatocelular dentro de los criterios de Milan [1 nódulo ≤5 cm o 3 nódulos ≤3 cm], cáncer de piel no-melanocítico, o cáncer de pecho o próstata controlado pueden ser incluidos. 10. Sujetos con insuficiencia cardíaca crónica (New York Heart Association [NYHA]) 11. Sujetos con enfermedad pulmonar severa (grado III o IV) (Global Obstructive Lung Disease [GOLD]). 12. Sujetos con creatinina sérica >2.0 × valores normales ([VN] basados en los resultados locales de laboratorio obtenidos antes del alta. 13. Sujetos con nefropatía orgánica definida por los criterios del ICA. 14. Sujetos con desordenes psiquiátricos severos. 15. Sujetos con infección conocida del virus de la inmunodeficiencia humana (VIH) o que tengas signos y síntomas clínicos compatible con una infección del VIH actual. 16. Mujeres embarazadas, amamantando, o con posibilidades de tener hijos, que no quieran practicar un método anticonceptivo eficaz. 17. Sujetos con trasplante hepático previo. 18. Sujetos con hipersensibilidad a la albúmina conocida o sospechosa 19. Sujetos que participen en otro ensayo clínico en los 3 meses previos al screening 20. Sujetos con drogo adicción activa 21. Sujetos que en opinión del investigador, tengan problemas de cumplimiento con el protocolo y los procedimientos del protocolo |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is to compare the 1-year transplant-free survival in the intent-to-treat (ITT) population between the SMT + Albutein 20% treatment group and the SMT alone group. |
La variable primaria de la eficacia es comparar la supervivencia libre de trasplante a 1 año en la población con intención de tratar (ITT) entre el grupo tratado con TME + Albutein 20% y el grupo TME solo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are to assess the effects of SMT + Albutein 20% treatment versus SMT alone on: 1) 3- and 6-month transplant-free and overall survival, 2) 1-year overall survival, and 3) total number of paracenteses and the incidence of refractory ascites. |
Las variables secundarias de eficacia son evaluar los efectos del tratamiento con SMT + Albutein al 20% versus SMT en: 1) supervivencia global y libre de trasplantes a 3 y 6 meses, 2) supervivencia global a 1 año y 3) número total de paracentesis y la incidencia de ascitis refractaria. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 and 6 months and 1 year. |
3 y 6 meses y 1 año. |
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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 |
Standard Medical Treatment according to the local guidelines |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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LPLV |
Último paciente última visita |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |