CirrhosisPhase 3ChildbenoxNCT02271295
Impact on Morbidity and Mortality of Prophylactic Dosing of Low Molecular Heparin in Child-Pugh B Cirrhotic Patients
A Phase 3 study testing Enoxaparine in people with Cirrhosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cirrhosis
- What is being tested?
- Enoxaparine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteFrance
- Study dates
- 27 Jul 2015to 2 Jul 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
Read the 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.
- Conditions
- Cirrhosis
- Being tested
- Enoxaparine
- Keywords
- Cirrhosis, Child B, decompensation, mortality, portal thrombosis, anticoagulation
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnoxaparineDrug
Also called LOVENOX® 4000UI/day
Enoxaparine 4000UI/day during 24 months
| Study group | Role | What they receive |
|---|---|---|
| Enoxaparine | Experimental | 69 Child Pugh B7-C10, cirrhotic patients receiving anticoagulation treatment (daily subcutaneous injection of enoxaparin 4000UI/day) during 24 months Receives: Drug: Enoxaparine |
| Control | No intervention | 69 Child Pugh B7-C10, cirrhotic patients not receiving anticoagulation treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morbidity and mortality at 24 months
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.
Measured: 24 months
Secondary outcomes (7)
Mortality liver-related or not at 24 months
Two year overall survival and two year liver related survival considering non-liver death as a competive event.
Measured: 24 months
Adverse events at 24 months
percentage of bleeding episodes not reported to portal hypertension, percentage of heparin induced thrombocytopenia, variation of bone mineral density (M24-M0/M0) and percentage of occurrence of osteoporosis at dual energy X-ray absorptiometry
Measured: 24 months
Liver function and fibrosis at 24 months
- Variation of liver function tests (M24-M0/M0): PT, albumin and T bilirubin levels, Child-Pugh and MELD score
- Variation of non-invasive tests of liver fibrosis (M24-M0/M0): fibrometer and cirrhometer scores, liver stiffness measurement using transient elastography.
Measured: 24 months
Thrombosis at 24 months
Occurrence of portal vein (PV) thrombosis at Doppler ultrasound evaluation performed every 3 months or CT scan performed at M-1 and M24 (appendix 2) or hepatocellular carcinoma at Doppler ultrasound evaluation performed every 3 months or CT scan performed at M-1 and M24 and confirmed according to EASL recommendations
Measured: 24 months
Compliance
record of unused packaging and information about compliance in a patient diary
Measured: 24 months
Survival rate without completion
Survival rate without complication 6 months after completion of treatment as well as variation of liver function and portal hypertension parameters, occurrence of PV thrombosis, occurrence of bacterial infections
Measured: 30 months
Portal hypertension parameters
Variation of portal hypertension parameters (M24-M0/M0): platelets count, esophageal varices size at endoscopic evaluation
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2014 (estimated)
- Study start27 Jul 2015
- Primary completion2 Jul 2019 (estimated)
- Study completion2 Jul 2019 (estimated)
Why it stopped: Premature discontinuation of inclusions by the sponsor for low inclusion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Armelle Poujol-Robert, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02271295
- Sponsor's protocol ID
- P130926
- Other IDs
- AOM 13606
- Acronym
- Childbenox
- Status last verified
- Feb 2018
- First submitted
- 20 Oct 2014
- Last updated
- 27 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02271295
- Acronym / sponsor ID
- Childbenox / P130926
- Conditions
- Cirrhosis
- Keywords
- Cirrhosis, Child B, decompensation, mortality, portal thrombosis, anticoagulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Premature discontinuation of inclusions by the sponsor for low inclusion
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Jul 2015 (actual)
- Primary completion
- 2 Jul 2019 (estimated)
- Study completion
- 2 Jul 2019 (estimated)
- First posted
- 22 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enoxaparine | Experimental | Drug: Enoxaparine69 Child Pugh B7-C10, cirrhotic patients receiving anticoagulation treatment (daily subcutaneous injection of enoxaparin 4000UI/day) during 24 months |
| Control | No intervention | –69 Child Pugh B7-C10, cirrhotic patients not receiving anticoagulation treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnoxaparineAlso: LOVENOX® 4000UI/dayEnoxaparine 4000UI/day during 24 months | Drug | Enoxaparine |
Primary outcome
Morbidity and mortality at 24 months
Time frame: 24 months
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.
7 secondary outcomes
Mortality liver-related or not at 24 months
Time frame: 24 months
Adverse events at 24 months
Time frame: 24 months
Liver function and fibrosis at 24 months
Time frame: 24 months
Thrombosis at 24 months
Time frame: 24 months
Compliance
Time frame: 24 months
Survival rate without completion
Time frame: 30 months
Portal hypertension parameters
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Armelle Poujol-Robert principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enoxaparine in people with Cirrhosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 27 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Morbidity and mortality at 24 months (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2018.