Clinical trial NCT05895136: A Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial).
Official title: A Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: European Foundation for Study of Chronic Liver Failure
Sponsor class: OTHER
Collaborators: name: Horizon 2020 - European Commission
First posted: 2023-06-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: To assess the safety and tolerability of the combinatorial therapy in terms of TEAE (pulmonary edema, major bleeding and/or thrombocytopenia
timeFrame: from baseline to Day 90
Secondary outcomes:
measure: 90 and 180-days changes in prognostic scores of CLIF-Consortium Acute Decompensation score (CLIF-C AD) from baseline.
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease (MELD) from baseline.
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease - sodio (MELDNa) from baseline
timeFrame: 90 and 180-days from baseline
measure: 30 days, 90 and 180-days incidence of hospital readmission and ICU admission (causes and length of stay)
timeFrame: 30, 90 and 180-days
measure: 90 and 180-days incidence of ACLF according to the EASL-CLIF criteria
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days overall and transplant-free survival
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days incidence and cumulative number of therapeutic paracenteses
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days incidence of major complication of cirrhosis (grade 2-4 HE, portalhypertensive gastrointestinal bleedings, AKI, HRS-AKI, new-onset portal vein thrombosis)
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days incidence of proven bacterial infection
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: liver function variables: grade of ascites
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: liver function variables: grade of hepatic encephalopathy (West Haven)
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: liver function variables: grade of hepatic encephalopathy (ANT)
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: liver function variables: bilirrubin
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: liver function variables: albumin serum levels
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: renal function variables: BUN
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: renal function variables: serum creatinine
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: renal function variables: electrolites
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: renal function variables: GFR
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: lung function variables: respiratory rate
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: lung function variables: FIO2
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: lung function variables: pulse oxymetric saturation
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: coagulative variables: INR
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: coagulative variables: aPTT
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: coagulative variables: fibrinogen
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: coagulative variables: Platelet count
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: hemodynamic variables: arterial pressure
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in organ function from baseline: hemodynamic variables: heart rate.
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in frailty (Liver Frailty Index, LFI)
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in quality of life measure through European Quality of Life Five Dimension Five Levels (EQ-5D-5L)
timeFrame: 90 and 180-days from baseline
measure: 90 and 180-days changes in quality of life measure through Visual Analog Scale (VAS)
timeFrame: 90 and 180-days from baseline
measure: Total hospital costs during the 6-month period
timeFrame: 180-days from baseline
measure: Total hospital costs predictors during the 6-month period
timeFrame: 180-days from baseline
measure: Total hospital costs drivers during the 6-month period cost drivers
timeFrame: 180-days from baseline
Other outcomes:
Locations:
city: Clichy
country: France
facility: Hôpital Beaujon
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen AöR
city: Münster
country: Germany
facility: Universität Münster
city: Bologna
country: Italy
facility: IRCSS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant'Orsola
state: Emilia Romagna
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino"
state: Piemonte
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-VHIR
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona-FCRB
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References: