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) |
Gruppi 1 e 2: Soggetti con cirrosi con ACLF-1b, ACLF-2, o ACLF-3a diagnosticato al momento del ricovero oppure durante la degenza Gruppo 3: Soggetti con cirrosi ricoverati per scompenso acuto della cirrosi (ascite, encefalopatia epatica [HE], emorragia gastrointestinale, e/o infezioni batteriche). |
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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 |
Gruppi 1 e 2: Soggetti con cirrosi e con diagnosi di insufficienza epatica acuta su cronica Gruppo 3: Soggetti con cirrosi senza diagnosi di insufficienza epatica acuta su cronica |
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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 |
• Esaminare la patogenesi dell'infiammazione sistemica, dell'insufficienza d'organo (OF) e della ACLF nella cirrosi • Esplorare i meccanismi d'azione della PE-A 5% nei pazienti con ACLF |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Non applicabile |
|
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. |
I pazienti del gruppo 1 e del gruppo 2 devono presentare tutti i seguenti criteri di inclusione per essere eleggibili alla partecipazione allo studio ALADDIN: 1. Essere inclusi nei centri di studio europei dello studio APACHE che partecipano anche allo studio ALADDIN 2. Aver firmato il modulo di consenso informato (ICF) per la partecipazione allo studio ALADDIN
I pazienti del gruppo 3 devono presentare tutti i seguenti criteri di inclusione per essere eleggibili alla partecipazione allo studio ALADDIN: 1. Pazienti cirrotici, di sesso maschile o femminile, di età compresa tra i 18 e i 79 anni. 2. Ospedalizzati per AD di cirrosi (ascite, encefalopatia epatica [HE], emorragia gastrointestinale e/o infezioni batteriche). Le infezioni batteriche sono considerate AD di cirrosi solo nei pazienti con precedente storia di cirrosi scompensata. 3. Pazienti disposti e in grado di dare il consenso informato scritto o delegare un rappresentante autorizzato a rilasciare il consenso informato scritto a loro nome, conformemente alle leggi locali e alla politica dell'istituto. |
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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. |
I pazienti del gruppo 3 che presentano uno qualsiasi dei seguenti criteri di esclusione NON sono eleggibili per partecipare allo studio. 1. Pazienti con ACLF (di qualsiasi grado). 2. I pazienti con shock settico della durata >1 ora che non rispondono alla terapia di reintegrazione dei liquidi per via endovenosa (EV) o ai farmaci vasopressori. 3. Pazienti con infezione batterica o fungina attiva con instabilità emodinamica. 4. Pazienti con emorragia attiva o recente (se non controllata per >48 ore). 5. Pazienti con insufficienza renale cronica e attualmente in emodialisi. 6. Evidenza di lesione maligna attuale localmente avanzata o metastatica (possono essere inclusi i pazienti con carcinoma epatocellulare secondo i criteri di Milano [1 nodulo =5 cm o 3 noduli =3 cm] [Appendix 2], carcinoma cutaneo non melanocitico e carcinoma della mammella o della prostata controllato). 7. Pazienti con insufficienza cardiaca cronica grave (classe III o IV della New York Heart Association [NYHA]) (Appendix 3). 8. Pazienti con malattia polmonare grave (grado III o IV secondo i criteri della Global Obstructive Lung Disease [GOLD]) (Appendix 4). 9. Pazienti con miopatia grave del paziente critico, secondo la definizione clinica. 10. Soggetti con infezione nota da virus dell'immunodeficienza umana (HIV) oppure con segni e sintomi clinici compatibili con l'attuale infezione da HIV. 11. Donne in gravidanza 12. Pazienti sottoposti a precedente trapianto di fegato. 13. Pazienti in terapia antitrombotica o anticoagulante. 14. Partecipazione a un altro studio clinico entro almeno 30 giorni prima dello screening. 15. Pazienti con tossicodipendenza. 16. Pazienti con ordine di non rianimare. 17. Pazienti che, secondo lo sperimentatore, possono avere problemi di compliance con il protocollo e le sue procedure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Not applicable |
Non applicabile |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
Non applicabile |
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E.5.2 | Secondary end point(s) |
Not applicable |
Non applicabile |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
Non applicabile |
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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 |
Trattamento medico standard in accordo alla pratica locale |
Standard Medical Treatment according to the local guidelines |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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 | 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 |