Impact on Morbidity and Mortality of Prophylactic Dosing of Low Molecular Weight Heparin in Child-Pugh B Cirrhotic Patients: a Randomized Controlled Study
Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cirrhosis
Intervention: Enoxaparine (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s): Armelle Poujol-Robert, Principal Investigator, Affiliation: Assistance Publique - HĂ´pitaux de Paris
Overall contact: Armelle Poujol-Robert, Phone: 0033 (0)1 49 28 24 63, Email: armelle.poujol-robert@sat.aphp.fr
Summary
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
Clinical Details
Official title: Impact on Morbidity and Mortality of Prophylactic Dosing of Low Molecular Weight Heparin in Child-Pugh B Cirrhotic Patients: a Randomized Controlled Study
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Morbidity and mortality at 24 months
Secondary outcome: Mortality liver-related or not at 24 monthsAdverse events at 24 months Liver function and fibrosis at 24 months Thrombosis at 24 months Compliance Survival rate without completion Portal hypertension parameters
Detailed 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Armelle Poujol-Robert, Phone: 0033 (0)1 49 28 24 63, Email: armelle.poujol-robert@sat.aphp.fr
HĂ´pital Saint Antoine, Paris, France; Recruiting Armelle Poujol-Robert
Additional Information
Starting date: April 2015
Last updated: April 29, 2015
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