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

NCT05895136 | Recruiting Phase 2 DMC

• 1 other identifier: COMBAT
• Study Type: interventional
• Target: 90
• Locations: 5 countries
• Sites: 9

Brief Summary

The goal of this clinical trial is to determine primarily whether a combinatorial therapy based on the administration of human albumin and enoxaparin is safe and effective in patients with decompensated cirrhosis discharged from the hospital. The main questions it aims to answer are:

• Is this combinatorial therapy safe and tolerable?
• Is this combinatorial therapy effective?
• does this combinatorial therapy cost more or less than standard medical therapy? Participants will attend to study visits in which several test will be performed to asses disease evolution while they are taking study medication. Researchers will compare experimental group treated with combinatorial therapy plus standard treatment with control group treated with standard treatment to see if there are differences in the responses to the questions raised above.

Conditions

Liver Cirrhosis; Decompensated Cirrhosis of Liver; Acute on Chronic Liver Failure (ACLF)

Keywords

decompensated cirrhosis; Acute on Chronic Liver Failure (ACLF); Liver diseases; liver cirrhosis; Human Albumin; Enoxaparin

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of the combinatorial therapy in terms of TEAE (pulmonary edema, major bleeding and/or thrombocytopenia

  The safety and tolerability of the combinatorial therapy of human albumin and enoxaparin on top of SMT compared to SMT alone, from baseline to Day 90, will be evaluated as the percentage of subjects who discontinued the study drug due to at least 1 of the following treatment-emergent adverse events (TEAE): pulmonary edema, severe thrombocytopenia and/or major bleeding. These variables will be described (counts and percentage).

  from baseline to Day 90

Secondary Outcomes (33)

• 90 and 180-days changes in prognostic scores of CLIF-Consortium Acute Decompensation score (CLIF-C AD) from baseline.

  90 and 180-days from baseline

• 90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease (MELD) from baseline.

  90 and 180-days from baseline

• 90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease - sodio (MELDNa) from baseline

  90 and 180-days from baseline

• 30 days, 90 and 180-days incidence of hospital readmission and ICU admission (causes and length of stay)

  30, 90 and 180-days

• 90 and 180-days incidence of ACLF according to the EASL-CLIF criteria

  90 and 180-days from baseline

Study Arms (2)

Enoxaparin plus human albumin

EXPERIMENTAL

Cohort 1 will receive standard medical treatment plus a combinatorial therapy of enoxaparin and human Albumin.

Drug: Human albumin; Drug: Enoxaparin; Drug: Standard medical treatment

Standard medical treatment

ACTIVE COMPARATOR

Cohort 2 (control) will receive only standard medical treatment.

Drug: Standard medical treatment

Interventions

Human albumin DRUG

Human albumin solution is made from pooled human plasma. It is widely used as a plasma-expander in several disease conditions, such as liver cirrhosis and critically ill patients. ATC-Code: B05AA01

Enoxaparin plus human albumin

Enoxaparin DRUG

Enoxaparin is a drug that belongs to the group of anticoagulants. It exerts its antithrombotic activity by binding to antithrombin III (AT III). ATC-Code: B01AB05

Enoxaparin plus human albumin

Standard medical treatment DRUG

SMT will be considered non-study medication and is not specified in the protocol.

Enoxaparin plus human albumin; Standard medical treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years.
• 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).
• CLIF-C AD score ≥ 45 at admission or at any time during hospital stay.
• Recovery from AD and expected to be discharged within the next 72 hours.

You may not qualify if:

• 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
• Admission for planned diagnostic or therapeutic procedures
• Recent acute bleeding (unless the cause has been effectively treated and there is no evidence of ongoing bleeding for at least 5 days)
• Chronic bleeding requiring periodic blood transfusions
• Presence of an ongoing acute complication of the disease (i.e. hepatic encephalopathy \[grade III or IV\])
• Conditions with a high risk of haemorrhage, including haemorrhagic diathesis not related to liver disease
• Patients with INR \> 3.0
• Severe thrombocytopenia (\<30x10 9 /L)
• Ongoing chronic anticoagulation therapy or indication for starting anticoagulation due to hepatic and non-hepatic conditions
• Ongoing anti-platelets therapy.
• Active malignancy (except for hepatocellular carcinoma within the Milan criteria or non-melanocytic skin cancer)
• Antiviral treatment for hepatitis C, B and delta initiated in the last 6 months or planned to be initiated in the following 6 months
• Ongoing alcohol use disorder with an expected low adherence to protocol as judged by physician
• Previous liver transplantation
• Patients with TIPS or other surgical porto-caval shunts

Sponsors & Collaborators

• European Foundation for Study of Chronic Liver Failure: lead
• Horizon 2020 - European Commission: collaborator

Study Sites (9)

Hôpital Beaujon

Clichy, 92110, France

RECRUITING

Universitätsklinikum Aachen AöR

Aachen, 52074, Germany

RECRUITING

Universität Münster

Münster, 48149, Germany

RECRUITING

IRCSS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant'Orsola

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino"

Turin, Piedmont, 10126, Italy

RECRUITING

Hospital Universitari Vall d'Hebron-VHIR

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Clínic de Barcelona-FCRB

Barcelona, 08036, Spain

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis; Acute-On-Chronic Liver Failure; Liver Diseases

Interventions

Serum Albumin, Human; Enoxaparin

Condition Hierarchy (Ancestors)

Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure, Acute; Liver Failure; Hepatic Insufficiency

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Central Study Contacts

Anna Bosch

CONTACT

+34 93 227 14 03; anna.bosch@efclif.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The patients enrolled in the study will be divided in two cohorts: Cohort 1 will receive standard medical treatment plus a combinatorial therapy of enoxaparin and human Albumin. Cohort 2 (control) will receive only standard medical treatment.

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: June 8, 2023
• Study Start: July 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: March 19, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); FR (1); IT (2); ES (3); GB (1)