Back to resultsA Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial). (COMBAT)
Primary Purpose
Liver Cirrhosis
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Human albumin
Enoxaparin
Standard medical treatment
Sponsored by
About this trial
This is an interventional treatment trial for Liver Cirrhosis
Eligibility Criteria
Inclusion Criteria: 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 >= 50 at admission or at any time during hospital stay. Recovery from AD and expected to be discharged within the next 48-72 hours. Exclusion Criteria: Diagnosis of acute-on-chronic liver failure (ACLF) grade 2 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 evidence of ongoing bleeding has not been identified for at least 5 days) Chronic bleeding requiring periodic blood transfusions Severe thrombocytopenia (≤20x109/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 Chronic organic renal failure stage IV and V or estimated Glomerular Filtration Rate <20 ml/min according to the MDRD equations Chronic heart failure NYHA class III or IV Pulmonary disease GOLD III or IV Patients with a history of significant extrahepatic disease with life expectancy <6 months Severe psychiatric disorders Known allergy or intolerance to human albumin or enoxaparin Pregnancy and breast-feeding Expected low adherence to study protocol as judged by physician Refusal to participate (no signed informed consent) Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surrogate decision-maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Enoxaparin plus human albumin
Standard medical treatment
Arm Description
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.
Outcomes
Primary Outcome Measures
The percentage of subjects who experience at least 1 treatment-emergent AE (TEAE) or SAE.
A descriptive analysis will be performed for all safety parameters overall and by treatment arm at every study time-point. Categorical parameters will be presented by counts and percentages.
Continuous parameters will be summarized by means of the appropriate descriptive statistics (mean ± standard deviation or median and interquartile range). The main safety end-points will be descriptively compared between treatment arms.
The percentage of subjects who discontinue the study drug due to pulmonary edema and/or major bleeding according to the definition by Shulman et al
A descriptive analysis will be performed for all safety parameters overall and by treatment arm at every study time-point. Categorical parameters will be presented by counts and percentages.
Continuous parameters will be summarized by means of the appropriate descriptive statistics (mean ± standard deviation or median and interquartile range). The main safety end-points will be descriptively compared between treatment arms.
Secondary Outcome Measures
90 and 180-days changes in prognostic scores of CLIF-Consortium Acute Decompensation score (CLIF-C AD) from baseline.
Lower scores of CLIF-C AD (<45) indicate a better prognostic than greater values (>50). In the statistical analysis Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease (MELD) from baseline.
The MELD score ranges from six to 40 and is based on results from several lab tests. The higher the number, the more likely you are to receive a liver from a deceased donor when an organ becomes available.
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease - sodio (MELDNa) from baseline
The MELDNa score ranges from six to 40 and is based on results from several lab tests. The higher the number, the more likely you are to receive a liver from a deceased donor when an organ becomes available.
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
30 days, 90 and 180-days incidence of hospital readmission and ICU admission (causes and length of stay)
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days incidence of ACLF according to the EASL-CLIF criteria
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days overall and transplant-free survival
Overall and transplant-free survival will be analyzed by estimating Kaplan-Meier survival curves for each treatment arm. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days incidence and cumulative number of therapeutic paracenteses
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
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)
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days incidence of proven bacterial infection
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: liver function variables: grade of ascites
Grade of ascites according to the criteria of the International Club of Ascites.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: liver function variables: grade of hepatic encephalopathy (West Haven)
Grade of hepatic encephalopathy using the West Haven (score range 0, normal to 4, coma).
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: liver function variables: grade of hepatic encephalopathy (ANT)
Animal Naming Test (ANT): range from >15, normal to <10
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: liver function variables: bilirrubin
Bilirubin in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: liver function variables: albumin serum levels
Albumin serum levels in g/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: renal function variables: BUN
BUN in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: renal function variables: serum creatinine
Serum creatinine in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: renal function variables: electrolites
Electrolytes: Na, K, Ca (mmol/L). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: renal function variables: GFR
Glomerula Filtration Ratio (GFR) will be estimated by the Modification of Diet in Renal Disease (MDRD) equations.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: lung function variables: respiratory rate
Respiratory rate in breaths per minute. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: lung function variables: FIO2
Fraction of inspired oxygen (FIO2) in percentage (%). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: lung function variables: pulse oxymetric saturation
Pulse oxymetric saturation in percentage (%). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: coagulative variables: INR
International Normalized Ratio (INR). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: coagulative variables: aPTT
Activated partial thromboplastin time (aPTT) in seconds. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: coagulative variables: fibrinogen
Fibrinogen in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: coagulative variables: Platelet count
Platelet count in platelets per microliter. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: hemodynamic variables: arterial pressure
Systolic, diastolic and mean arterial pressure in mmHg. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in organ function from baseline: hemodynamic variables: heart rate.
Heart rate in beats per minute. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in frailty (Liver Frailty Index, LFI)
LFI score of ≤ 3.2 indicates a patient is robust, 3.3-4.4 pre frail and ≥ 4.5 frail.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in quality of life measure through European Quality of Life Five Dimension Five Levels (EQ-5D-5L)
EQ-5D-5L has a score from 5 (no problems) to 25 (extreme problems on all dimensions evaluated).
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
90 and 180-days changes in quality of life measure through Visual Analog Scale (VAS)
VAS has a score from 0 (worst health patient can imagine) to 100 (best health patient can imagine)
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Total hospital costs during the 6-month period
To estimate the 90-days costs of an acute decompensation of cirrhosis for both arms in the trial
In-hospital resource utilization will be described based on diagnosis and procedural codes and length of stay. Hospital costs will be assigned based on the primary indication for hospitalization and procedures performed during the hospitalization and the Severity-Diagnosis Related Groups. Costs will be then assigned based on the latest mean cost available.
Costs will be calculated in euros by treatment arm.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Total hospital costs predictors during the 6-month period
To identify cost predictors (patients characteristics that are present before the treatment is initiated) and
In-hospital resource utilization will be described based on diagnosis and procedural codes and length of stay. Hospital costs will be assigned based on the primary indication for hospitalization and procedures performed during the hospitalization and the Severity-Diagnosis Related Groups. Costs will be then assigned based on the latest mean cost available.
Costs will be calculated in euros by treatment arm.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Total hospital costs drivers during the 6-month period cost drivers
Cost drivers (response to treatment, randomization arm, other treatments).
In-hospital resource utilization will be described based on diagnosis and procedural codes and length of stay. Hospital costs will be assigned based on the primary indication for hospitalization and procedures performed during the hospitalization and the Severity-Diagnosis Related Groups. Costs will be then assigned based on the latest mean cost available.
Costs will be calculated in euros by treatment arm.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Full Information
NCT ID
NCT05895136
First Posted
May 11, 2023
Last Updated
June 6, 2023
Sponsor
European Foundation for Study of Chronic Liver Failure
1. Study Identification
Unique Protocol Identification Number
NCT05895136
Brief Title
A Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial).
Acronym
COMBAT
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
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Foundation for Study of Chronic Liver Failure
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Enoxaparin plus human albumin
Arm Type
Experimental
Arm Description
Cohort 1 will receive standard medical treatment plus a combinatorial therapy of enoxaparin and human Albumin.
Arm Title
Standard medical treatment
Arm Type
Active Comparator
Arm Description
Cohort 2 (control) will receive only standard medical treatment.
Intervention Type
Drug
Intervention Name(s)
Human albumin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Enoxaparin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Standard medical treatment
Intervention Description
SMT will be considered non-study medication and is not specified in the protocol.
Primary Outcome Measure Information:
Title
The percentage of subjects who experience at least 1 treatment-emergent AE (TEAE) or SAE.
Description
A descriptive analysis will be performed for all safety parameters overall and by treatment arm at every study time-point. Categorical parameters will be presented by counts and percentages.
Continuous parameters will be summarized by means of the appropriate descriptive statistics (mean ± standard deviation or median and interquartile range). The main safety end-points will be descriptively compared between treatment arms.
Time Frame
from baseline to Day 90
Title
The percentage of subjects who discontinue the study drug due to pulmonary edema and/or major bleeding according to the definition by Shulman et al
Description
A descriptive analysis will be performed for all safety parameters overall and by treatment arm at every study time-point. Categorical parameters will be presented by counts and percentages.
Continuous parameters will be summarized by means of the appropriate descriptive statistics (mean ± standard deviation or median and interquartile range). The main safety end-points will be descriptively compared between treatment arms.
Time Frame
from baseline to Day 90
Secondary Outcome Measure Information:
Title
90 and 180-days changes in prognostic scores of CLIF-Consortium Acute Decompensation score (CLIF-C AD) from baseline.
Description
Lower scores of CLIF-C AD (<45) indicate a better prognostic than greater values (>50). In the statistical analysis Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease (MELD) from baseline.
Description
The MELD score ranges from six to 40 and is based on results from several lab tests. The higher the number, the more likely you are to receive a liver from a deceased donor when an organ becomes available.
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in prognostic scores of Mayo End stage Liver Disease - sodio (MELDNa) from baseline
Description
The MELDNa score ranges from six to 40 and is based on results from several lab tests. The higher the number, the more likely you are to receive a liver from a deceased donor when an organ becomes available.
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
30 days, 90 and 180-days incidence of hospital readmission and ICU admission (causes and length of stay)
Description
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
30, 90 and 180-days
Title
90 and 180-days incidence of ACLF according to the EASL-CLIF criteria
Description
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days overall and transplant-free survival
Description
Overall and transplant-free survival will be analyzed by estimating Kaplan-Meier survival curves for each treatment arm. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days incidence and cumulative number of therapeutic paracenteses
Description
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
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)
Description
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days incidence of proven bacterial infection
Description
Chi-Square test or Fisher exact test will be performed. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: liver function variables: grade of ascites
Description
Grade of ascites according to the criteria of the International Club of Ascites.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: liver function variables: grade of hepatic encephalopathy (West Haven)
Description
Grade of hepatic encephalopathy using the West Haven (score range 0, normal to 4, coma).
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: liver function variables: grade of hepatic encephalopathy (ANT)
Description
Animal Naming Test (ANT): range from >15, normal to <10
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: liver function variables: bilirrubin
Description
Bilirubin in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: liver function variables: albumin serum levels
Description
Albumin serum levels in g/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: renal function variables: BUN
Description
BUN in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: renal function variables: serum creatinine
Description
Serum creatinine in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: renal function variables: electrolites
Description
Electrolytes: Na, K, Ca (mmol/L). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: renal function variables: GFR
Description
Glomerula Filtration Ratio (GFR) will be estimated by the Modification of Diet in Renal Disease (MDRD) equations.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: lung function variables: respiratory rate
Description
Respiratory rate in breaths per minute. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: lung function variables: FIO2
Description
Fraction of inspired oxygen (FIO2) in percentage (%). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: lung function variables: pulse oxymetric saturation
Description
Pulse oxymetric saturation in percentage (%). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: coagulative variables: INR
Description
International Normalized Ratio (INR). Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: coagulative variables: aPTT
Description
Activated partial thromboplastin time (aPTT) in seconds. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: coagulative variables: fibrinogen
Description
Fibrinogen in mg/dL. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: coagulative variables: Platelet count
Description
Platelet count in platelets per microliter. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: hemodynamic variables: arterial pressure
Description
Systolic, diastolic and mean arterial pressure in mmHg. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in organ function from baseline: hemodynamic variables: heart rate.
Description
Heart rate in beats per minute. Ranges according reference ranges of each study site.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in frailty (Liver Frailty Index, LFI)
Description
LFI score of ≤ 3.2 indicates a patient is robust, 3.3-4.4 pre frail and ≥ 4.5 frail.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in quality of life measure through European Quality of Life Five Dimension Five Levels (EQ-5D-5L)
Description
EQ-5D-5L has a score from 5 (no problems) to 25 (extreme problems on all dimensions evaluated).
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
90 and 180-days changes in quality of life measure through Visual Analog Scale (VAS)
Description
VAS has a score from 0 (worst health patient can imagine) to 100 (best health patient can imagine)
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
90 and 180-days from baseline
Title
Total hospital costs during the 6-month period
Description
To estimate the 90-days costs of an acute decompensation of cirrhosis for both arms in the trial
In-hospital resource utilization will be described based on diagnosis and procedural codes and length of stay. Hospital costs will be assigned based on the primary indication for hospitalization and procedures performed during the hospitalization and the Severity-Diagnosis Related Groups. Costs will be then assigned based on the latest mean cost available.
Costs will be calculated in euros by treatment arm.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
180-days from baseline
Title
Total hospital costs predictors during the 6-month period
Description
To identify cost predictors (patients characteristics that are present before the treatment is initiated) and
In-hospital resource utilization will be described based on diagnosis and procedural codes and length of stay. Hospital costs will be assigned based on the primary indication for hospitalization and procedures performed during the hospitalization and the Severity-Diagnosis Related Groups. Costs will be then assigned based on the latest mean cost available.
Costs will be calculated in euros by treatment arm.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
180-days from baseline
Title
Total hospital costs drivers during the 6-month period cost drivers
Description
Cost drivers (response to treatment, randomization arm, other treatments).
In-hospital resource utilization will be described based on diagnosis and procedural codes and length of stay. Hospital costs will be assigned based on the primary indication for hospitalization and procedures performed during the hospitalization and the Severity-Diagnosis Related Groups. Costs will be then assigned based on the latest mean cost available.
Costs will be calculated in euros by treatment arm.
Student t-test or analysis of variance will be used to compare normally distributed variable or non-parametric methods if the assumptions of normality are not met. Pairwise Log-rank tests will be used for statistical comparisons.
Time Frame
180-days from baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 >= 50 at admission or at any time during hospital stay.
Recovery from AD and expected to be discharged within the next 48-72 hours.
Exclusion Criteria:
Diagnosis of acute-on-chronic liver failure (ACLF) grade 2 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 evidence of ongoing bleeding has not been identified for at least 5 days)
Chronic bleeding requiring periodic blood transfusions
Severe thrombocytopenia (≤20x109/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
Chronic organic renal failure stage IV and V or estimated Glomerular Filtration Rate <20 ml/min according to the MDRD equations
Chronic heart failure NYHA class III or IV
Pulmonary disease GOLD III or IV
Patients with a history of significant extrahepatic disease with life expectancy <6 months
Severe psychiatric disorders
Known allergy or intolerance to human albumin or enoxaparin
Pregnancy and breast-feeding
Expected low adherence to study protocol as judged by physician
Refusal to participate (no signed informed consent)
Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surrogate decision-maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Bosch
Phone
+34 93 227 14 03
Email
anna.bosch@efclif.com
12. IPD Sharing Statement
Learn more about this trial
A Novel COMBinATorial Therapy With Albumin and Enoxaparin in Patients With Decompensated Cirrhosis at High-risk of Poor Outcome (COMBAT Trial).
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