Combining Albumin and Enoxaparin for Patients with Decompensated Cirrhosis

A Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial).

This study is testing a new treatment that combines albumin and enoxaparin to see if it helps people with severe liver disease feel better compared to standard care.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: European Foundation for Study of Chronic Liver Failure (Academic / other)
• Locations: 9 sites (Clichy and 8 other locations)
• Trial ID: NCT05895136 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and effectiveness of a novel combinatorial therapy using human albumin and enoxaparin in patients with decompensated cirrhosis who are at high risk of poor outcomes. Participants will be divided into two groups: one receiving the combinatorial therapy alongside standard treatment, and the other receiving only standard treatment. The study aims to assess the tolerability of the therapy, its effectiveness in improving patient outcomes, and its cost compared to standard medical therapy. Regular study visits will be conducted to monitor disease progression and response to treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with decompensated cirrhosis who are recovering from acute decompensation and are expected to be discharged from the hospital soon.

Not a fit: Patients with acute-on-chronic liver failure grade 3 or higher or those with ongoing acute complications of the disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve outcomes for patients with decompensated cirrhosis, potentially reducing hospital readmissions and enhancing quality of life.

How similar studies have performed: While this approach is novel, similar studies exploring combinatorial therapies in liver diseases have shown promising results, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 and 80 years.
2. Patients with decompensated cirrhosis admitted to hospital due to AD according to the EASL-CLIF criteria (rapid onset of ascites, hepatic encephalopathy, portal hypertensive-related gastrointestinal bleeding, bacterial infection, or any combination of these).
3. CLIF-C AD score ≥ 45 at admission or at any time during hospital stay.
4. Recovery from AD and expected to be discharged within the next 72 hours.

Exclusion Criteria:

1. Diagnosis of acute-on-chronic liver failure (ACLF) grade 3 or higher according to the EASL-CLIF criteria at admission or at any time during the index hospitalization
2. Admission for planned diagnostic or therapeutic procedures
3. Recent acute bleeding (unless the cause has been effectively treated and there is no evidence of ongoing bleeding for at least 5 days)
4. Chronic bleeding requiring periodic blood transfusions
5. Presence of an ongoing acute complication of the disease (i.e. hepatic encephalopathy \[grade III or IV\])
6. Conditions with a high risk of haemorrhage, including haemorrhagic diathesis not related to liver disease
7. Patients with INR \> 3.0
8. Severe thrombocytopenia (\<30x10 9 /L)
9. Ongoing chronic anticoagulation therapy or indication for starting anticoagulation due to hepatic and non-hepatic conditions
10. Ongoing anti-platelets therapy.
11. Active malignancy (except for hepatocellular carcinoma within the Milan criteria or non-melanocytic skin cancer)
12. Antiviral treatment for hepatitis C, B and delta initiated in the last 6 months or planned to be initiated in the following 6 months
13. Ongoing alcohol use disorder with an expected low adherence to protocol as judged by physician
14. Previous liver transplantation
15. Patients with TIPS or other surgical porto-caval shunts
16. Chronic organic renal failure stage IV and V or estimated Glomerular Filtration Rate \<30 ml/min according to the MDRD equations
17. Chronic heart failure NYHA class III or IV
18. Pulmonary disease GOLD III or IV
19. Patients with extrahepatic diseases with life expectancy \<6 months
20. Severe psychiatric disorders
21. Hypersensitivity to albumin preparations or to any of the excipients.
22. Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWH) or to any of the excipients
23. History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies
24. Pregnancy and breast-feeding
25. Expected low adherence to study protocol as judged by physician
26. Patients who can't provide written informed consent or refusal to participate
27. Participation in other concurrent clinical trials and within the prior 3 months from informed consent signature.

Where this trial is running

Clichy and 8 other locations

• Hôpital Beaujon — Clichy, France (Recruiting)
• Universitätsklinikum Aachen AöR — Aachen, Germany (Recruiting)
• Universität Münster — Münster, Germany (Recruiting)
• IRCSS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant'Orsola — Bologna, Emilia-Romagna, Italy (Recruiting)
• Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino" — Turin, Piedmont, Italy (Recruiting)
• Hospital Universitari Vall d'Hebron-VHIR — Barcelona, Barcelona, Spain (Recruiting)
• Hospital Universitario Ramón y Cajal — Madrid, Madrid, Spain (Recruiting)
• Hospital Clínic de Barcelona-FCRB — Barcelona, Spain (Recruiting)
• Royal Free Hospital — London, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Anna Bosch

Conditions Liver Cirrhosis; Decompensated Cirrhosis of Liver; Acute on Chronic Liver Failure; decompensated cirrhosis; Liver diseases; liver cirrhosis; Human Albumin; Enoxaparin