E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Group 1 and 2: Subjects with cirrhosis with ACLF-1b, ACLF-2, or ACLF-3a detected either at admission or during hospitalization
Group 3: Subject with cirrhosis hospitalized for Acute decompensation of cirrhosis (ascites, hepatic encephalopathy [HE], gastrointestinal hemorrhage, and/or bacterial infections) |
Grupo 1 y grupo 2: pacientes con cirrosis con ACLF-1b, ACLF-2, o ACLF-3a detectada a su ingreso o durante su hospitalización Grupo 3: pacientes con cirrosis hospitalizados for descompensación aguda de la cirrosis (ascitis, encefalopatía hepática, hemorragea gastrointestinal, i /o infecciones bacterianas) |
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E.1.1.1 | Medical condition in easily understood language |
Group 1 and 2: Subjects with cirrhosis and diagnosed Acute-on-Chronic Liver Failure Group 3: Subjects with cirrhosis without diagnosed Acute-on-Chronic Liver Failure |
Grupo 1 y grupo 2: pacientes con cirrosis y diagnosticado con ACLF. Grupo 3: pacientes con cirrosis sin ACLF diagnosticado. |
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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 | 20.1 |
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 investigate the pathogenesis of systemic inflammation, organ failure (OF), and ACLF in cirrhosis To explore mechanisms of action of PE-A 5% in subjects with ACLF |
Investigar la patogénesis de la inflamación sistémica, el fallo orgánico (FO) y la ACLF en la cirrosis Explorar los mecanismos de acción del recambio plasmático con albúmina sérica humana (5%) en pacientes con ACLF. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects enrolled in Group 1 and 2 must meet all the following inclusion criteria to be eligible for participation in this study: 1. Be enrolled at European study centers of the APACHE study which are also participating in the ALADDIN study. 2. Have signed the informed consent form (ICF) to participate in the ALADDIN study.
Subjects enrolled in Group 3 must meet all the following inclusion criteria to be eligible for participation in this study: 1. Male or female cirrhotic subject between 18 and 79 years of age. 2. Hospitalized for AD of cirrhosis (ascites, HE, gastrointestinal hemorrhage and/or bacterial infections). Bacterial infections are considered an AD of cirrhosis only in subjects with prior history of decompensated cirrhosis. 3. 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. |
Los pacientes del Grupo 1 y del Grupo 2 deben cumplir todos los siguientes criterios de inclusión para ser elegibles para la participación en el mismo, como sigue: 1. Estar incluidos en centros que participan en el estudio APACHE en Europa y que los mismos estén participando también en el estudio ALADDIN 2. Haber firmado el documento de consentimiento informado (DCI) para la participación en el estudio ALADDIN. Los pacientes del Grupo 3 deben cumplir todos los siguientes criterios de inclusión para ser elegibles para la participación en este estudio. 1. Pacientes cirróticos varones o mujeres de 18 a 79 años de edad. 2. Hospitalizados por DA de la cirrosis (ascitis, encefalopatía hepática [EH], hemorragia gastrointestinal y/o infecciones bacterianas). Las infecciones bacterianas se consideran DA de la cirrosis solo en pacientes con antecedentes previos de cirrosis descompensada. 3. Dispuestos y capaces de dar su consentimiento informado por escrito o tener un representante autorizado capaz de dar su consentimiento informado por escrito en nombre del paciente, de acuerdo con la ley y la política institucional locales. |
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E.4 | Principal exclusion criteria |
Subjects in Group 3 meeting any of the following exclusion criteria are NOT eligible for participation in the study: 1. Subjects with ACLF (any grade). 2. Subjects with septic shock lasting >1 hour that does not respond to fluid resuscitation intravenous (IV) therapy or pharmacologic-pressors. 3. Subjects with active bacterial or fungal infection with hemodynamic instability. 4. Subjects with active or recent bleeding (unless controlled for >48 hours). 5. Subjects with chronic renal failure and currently receiving hemodialysis. 6. 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, and controlled breast or prostate cancer, can be included). 7. Subjects with severe chronic heart failure (New York Heart Association [NYHA] class III or IV). 8. Subjects with severe pulmonary disease (Global Obstructive Lung Disease [GOLD] stage III or IV). 9. Subjects with severe critical illness myopathy as defined clinically. 10. Subjects with a known infection with human immunodeficiency virus (HIV) or clinical signs and symptoms consistent with current HIV infection. 11. Females who are pregnant. 12. Subjects with previous liver transplantation. 13. Subjects receiving anti-platelet or anti-coagulant therapy. 14. Participation in another clinical study within at least 30 days prior to screening. 15. Subjects with active drug addiction. 16. Subjects with a do-not-resuscitate order. 17. Subjects who, in the opinion of the investigator, may have compliance problems with the protocol and the procedures of the protocol. |
Los pacientes del Grupo 3 que cumplan cualquiera de los siguientes criterios de exclusión NO son elegibles para la participación en el estudio. 1. Pacientes con ACLF (de cualquier grado). 2. Pacientes con shock séptico que dure >1 hora que no responda a tratamiento intravenoso (IV) de reanimación con líquido o fármacos vasopresores. 3. Pacientes con infección bacteriana o fúngica activa con inestabilidad hemodinámica. 4. Pacientes con sangrado activo o reciente (a menos que esté controlada durante >48 horas). 5. Pacientes con insuficiencia renal crónica y que actualmente reciben hemodiálisis. 6. Pruebas de neoplasia maligna actual, localmente avanzada o metastásica (pueden incluirse pacientes con carcinoma hepatocelular dentro de los criterios de Milán [1 nódulo ≤5 cm o 3 nódulos ≤3 cm], cáncer de piel no melanocítico y cáncer de mama o de próstata controlado). 7. Pacientes con insuficiencia cardíaca crónica grave (clase III o IV de la New York Heart Association [NYHA]). 8. Pacientes con enfermedad pulmonar grave (Estadio III o IV de la escala Enfermedad Pulmonar Obstructiva Global (Global Obstructive Lung Disease [GOLD] stage III or IV). 9. Pacientes con miopatía con enfermedad crítica grave según definición clínica. 10. Pacientes con infección conocida por virus de la inmunodeficiencia humana (VIH) o signos y síntomas clínicos coherentes con infección actual por VIH. 11. Mujeres embarazadas. 12. Pacientes con trasplante hepático previo. 13. Pacientes que reciben tratamiento antiplaquetario o anticoagulante. 14. Participación en otro estudio clínico dentro del plazo de 30 días antes de la exploración. 15. Pacientes con adicción activa a drogas. 16. Pacientes con una orden de no reanimación. 17. Pacientes que, en opinión del investigador, pueden tener problemas de cumplimiento del protocolo o los procedimientos del protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
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 |
tratamiento médico estándar (TME) |
Standard Medical Treatment according to the local guidelines |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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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LVLS |
Última visita del último paciente |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |