Acute-On-Chronic Liver Failure (ACLF) at High Risk of Hospital Mortality

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 380

Inclusion Criteria

1. Male or female cirrhotic subjects between 18 and 79 years of age.
2. Subjects with ACLF-1b, ACLF-2, or ACLF-3a detected either at admission or during
hospitalization (must be ACLF-1b, -2, or -3a within the Screening Period [a maximum of
10 days]) (see Table 2-1 for ACLF grades in the study protocol).
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.
4. In case of HE, informed consent will be provided by a relative or a legally authorized
representative (surrogate).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

1. Subjects without ACLF.
2. Subjects with ACLF-1a or ACLF-3b (see Table 2-1 for ACLF grades in the study protocol) after the Screening
Period.
3. Subjects fulfilling inclusion criteria that improve to no ACLF or to ACLF-1a or worsen
to ACLF-3b during the Screening Period (between initial evaluation and time of randomization).
4. Subjects with ACLF for more than 10 days prior to randomization.
5. Subjects with acute or subacute liver failure without underlying cirrhosis.
6v3. Subjects with septic shock requiring use of norepinephrine (> 0.3 mcg/kg/min) need for a second vasopressor (including terlipressin).
7v3. Subjects with active bacterial or fungal infection : who have received less than 24h of appropriate antibiotic treatment.
8v3. Subjects with severe respiratory failure with PaO2/FiO2 =200.
9. Subjects with active or recent bleeding (unless controlled for >48 hours).
10. Subjects with severe thrombocytopenia (=20×109/L) (based on local laboratory assessment).
11. Subjects with chronic renal failure and currently receiving hemodialysis.
12. 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 [Appendix 5 of the study protocol]), non-melanocytic skin cancer, and controlled breast or prostate cancer can be included).
13. Subjects with severe chronic heart failure (New York Heart Association [NYHA] class III or IV) (Appendix 6 of the study protocol).
14. Subjects with severe pulmonary disease (Global Obstructive Lung Disease [GOLD] stage III or IV) (Appendix 7 of the study protocol).
15. Subjects with severe myopathy as defined clinically.
16. Subjects with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection.
17. Females who are pregnant, breastfeeding, or if of childbearing potential, unwilling to practice a highly effective method of contraception (oral, injectable, or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom, or occlusive cap with spermicidal foam/gel/cream/suppository, male sterilization, or true abstinence*) throughout the study.
* True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception).
18. Subjects with previous liver transplantation.
19v3. Subjects receiving anti-platelet or anti-coagulant therapy (low-molecular-weight heparin [LMWH] for deep vein thrombosis [DVT] prophylaxis is allowed).
20. Participation in another clinical study within at least 30 days prior to screening.
21v3. Subjects with active drug addiction (exceptions: active alcoholism or marijuana)
22. Subjects with a do-not-resuscitate order.
23. In the opinion of the investigator, the subject may have compliance problems with the
protocol and the procedures of the protocol.
24. Subjects with current infection of COVID19, those who are less than 14 days post recovery or those who have clinical signs and symptoms consistent with COVID19 infection.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate the effect of standard medical treatment (SMT) plus PE-A 5% (SMT+PE-A 5%) on 90-day overall survival.;Secondary Objective: - To evaluate the effect of SMT+PE-A 5% on 90-day transplant-free survival.<br>- To evaluate the effect of SMT+PE-A 5% on 28-day overall survival.;Primary end point(s): The primary efficacy endpoint is to compare the 90-day overall survival in the intent-to-treat (ITT) population between the SMT+PE-A 5% treatment group and the SMT control group.;Timepoint(s) of evaluation of this end point: 90 days

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary efficacy endpoints are to assess the effects of PE-A 5% on: <br>1) 90-day transplant-free survival<br> and<br> 2) 28-day overall survival <br>versus SMT alone.;Timepoint(s) of evaluation of this end point: 28 and 90 days

Updated 9/26/2023

Acute-On-Chronic Liver Failure (ACLF) at High Risk of Hospital Mortality

Recruitment & Eligibility

Study & Design

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