Impact on Morbidity and Mortality of Prophylactic Dosing of Low Molecular Heparin in Child-Pugh B Cirrhotic Patients (Childbenox)

Assistance Publique - Hôpitaux de Paris

Status and phase

Suspended

Phase 3

Conditions

Cirrhosis

Treatments

Drug: Enoxaparine

Study type

Interventional

Funder types

Other

Identifiers

NCT02271295

P130926

AOM 13606 (Other Grant/Funding Number)

Details and patient eligibility

About

Thrombosis occurring in the small intrahepatic, as well as in the large vessels is involved in the progression of cirrhosis. Anticoagulation could reduce morbidity and mortality in cirrhotic patients

Full description

Cirrhosis is the end-stage of all chronic liver diseases. Cirrhosis is a critical step in the natural history of liver disease, as it is associated with the occurrence of complications (so-called decompensation) and death. Life expectancy varies from 12-14 years in patients with compensated cirrhosis, to 2-4 years after decompensation.

Cirrhosis is associated with thrombosis of the intrahepatic portal and hepatic venous systems leading to parenchymal extinction (atrophy), liver dysfunction and portal hypertension. Regeneration in the areas without microthrombosis, and inflammation are powerful factors inducing liver cancer. Portal and hepatic venous thrombosis have been shown to participate in remodeling the liver architecture and are associated with a worsening outcome. Thrombosis in cirrhosis is thought to result from a procoagulant state due to an imbalance between pro and anticoagulant factor plasma levels, inflammation in and around blood vessels, and a marked slowing down of venous blood flow. Heparin administration, in animal models of liver fibrosis, decreases extra cellular matrix protein synthesis and fibrous tissue deposition. Recently, a reduction in liver decompensation and mortality has been shown in Child-Pugh B7-C10 cirrhotic patients assigned to receive a low dose of enoxaparin (4000IU/d), a low molecular weight heparin, for 48 weeks, compared to patients receiving no anticoagulation therapy.

These results are in line with the hypothesis of a protective role of anticoagulation in liver disease progression and a strong association between thrombosis and liver fibrosis.

So the main objective of the study is to compare the effect of a 2-year low dosing of Enoxaparin (4000 IU/day) versus no treatment on morbidity and mortality in patients with Child B7-C10 cirrhosis.

Enrollment

16 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥18 and ≤75 years old
A diagnosis of cirrhosis based on liver biopsy or on the combination of clinical, laboratory and imaging criteria
Compensated Child-Pugh B7-C10
Any of the following causal factors : past but controlled excessive alcohol intake (<30g/d for men and <20g/d for women), HCV infection without viral replication, HBV infection without viral replication on therapy, metabolic syndrome, biliary cirrhosis, auto-immune cirrhosis, hemochromatosis, cryptogenetic cirrhosis

Exclusion criteria

Ascites, portal hypertensive bleeding or encephalopathy within the last 3 months prior to enrolment
Hepatocellular carcinoma non considered in remission
Budd Chiari syndrome non considered in remission
Liver transplantation
F2 or F3 varices without treatment in accordance with recommended guidelines (B-blockers, ligation or both)
Portal vein thrombosis
Transjugular intrahepatic portosystemic shunt
Known extra-hepatic malignancies
PT<35%
Platelet count<50,000/mm3
Haemoglobin level < 9g/dl
Serum Albumin < 20g/L
A bone mineral density T score of less than -4.0 at the lumbar spine or total hip
Known HIV infection
Ongoing anticoagulation or antiaggregation
Renal insufficiency defined by creatinine clearance<60ml/mn
Conditions at risk for spontaneous bleeding (except for portal hypertension) or hemostatic abnormalities not related to cirrhosis
Pregnancy or breast-feeding