A Novel COMBinATorial Therapy With Albumin and Enoxaparin... | NCT05895136

NCT05895136

Status Module

Name	Class
Horizon 2020 - European Commission	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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 from baseline

Eligibility Module

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 ≥ 45 at admission or at any time during hospital stay.
Recovery from AD and expected to be discharged within the next 72 hours.

Exclusion Criteria:

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
Chronic organic renal failure stage IV and V or estimated Glomerular Filtration Rate <30 ml/min according to the MDRD equations
Chronic heart failure NYHA class III or IV
Pulmonary disease GOLD III or IV
Patients with extrahepatic diseases with life expectancy <6 months
Severe psychiatric disorders
Hypersensitivity to albumin preparations or to any of the excipients.
Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWH) or to any of the excipients
History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies
Pregnancy and breast-feeding
Expected low adherence to study protocol as judged by physician
Patients who can't provide written informed consent or refusal to participate
Participation in other concurrent clinical trials and within the prior 3 months from informed consent signature.

ID	Term
D008103	Liver Cirrhosis
D065290	Acute-On-Chronic Liver Failure
D008107	Liver Diseases

ID	Term
D004066	Digestive System Diseases
D005355	Fibrosis
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D017114	Liver Failure, Acute
D017093	Liver Failure
D048550	Hepatic Insufficiency

ID	Term
D000075462	Serum Albumin, Human
D017984	Enoxaparin

ID	Term
D012709	Serum Albumin
D000418	Albumins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D001798	Blood Proteins
D006495	Heparin, Low-Molecular-Weight
D006493	Heparin
D006025	Glycosaminoglycans
D011134	Polysaccharides
D002241	Carbohydrates