Alcoholic CirrhosisPhase 3CIRROXNCT01342705
Phlebotomy and Risk of Hepatocellular Carcinoma in Patients With Compensated Alcoholic Cirrhosis
A Phase 3 study testing phlebotomy in people with Alcoholic Cirrhosis and Iron Overload, run by Assistance Publique - Hôpitaux de Paris at 14 sites in France.
Trial summary
The main objective of the study is to assess in patients with compensated alcoholic cirrhosis and hepatic iron overload (HIO), as assessed by MRI, the effect of phlebotomy in order to lower and maintain serum ferritin below 50 µg / l on the risk of hepatocellular carcinoma (HCC) occurrence. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholic Cirrhosis, Iron Overload
- What is being tested?
- phlebotomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 14 sitesFrance
- Study dates
- May 2011to Jun 2014
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age over 18
- Biopsy-proven alcoholic cirrhosis
- No previous HCC (treated or not)
- Excessive alcohol consumption, defined by more than 21 glasses weekly in women and more than 28 glasses weekly in men for at least 10 years, and considered as the main cause for liver cirrhosis
- Signed written informed consent
- Hepatic iron overload assessed by MRI (Iron hepatic concentration ≥ 80 μmol/g)
Who cannot join
- Subjects deprived of their liberty by judicial or administrative decision
- Pregnant women
- Serious associated short-term life threatening disease (except HIV viral co-infection, or the liver disease itself)
- Impossibility of monitoring, whatever the reason.
- Contraindication of phlebotomy
- Haemoglobin <13.5 g/dL for men and <12.5g/dL for women (threshold established by the French Blood Agency)
Show all 13Show fewer
- Congestive heart failure or coronary heart disease
- Hepatic failure (TP<60%), renal failure (GFR <50 ml/min) or respiratory insufficiency (chronic dyspnea)
- Poor venous system
- Complication of cirrhosis at time of inclusion (defined as bleeding related to portal hypertension, encephalopathy or ascites)
- Presence of hepatitis B or hepatitis C co-infection
- Presence of liver focal lesion suggestive of HCC
- Child-Pugh score greater than or equal to 7 (Class B or C) at time of inclusion
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
France14 sites
Amiens University Hospital :
Amiens
Avicenne
Bobigny
Jean Verdier
Bondy, 93140
CHU Bordeaux univerity hospital 1
Bordeaux
CHU Bordeaux University hospital 2
Bordeaux
CHU
Caen
Antoine Béclère
Clamart
CHU
Grenoble
CHU
Lille
CHU
Montpellier
CHU
Nancy
CHU
Nice
CHU
Rennes
CHU
Rouen
About this study
Official title: Influence of Iron Depletion by Phlebotomy on the Risk of Hepatocellular Carcinoma Occurrence in Patients With Compensated Alcoholic Cirrhosis. Prospective, Multicentre, Randomized Trial
The main objective of the study is to assess in patients with compensated alcoholic cirrhosis and hepatic iron overload (HIO), as assessed by MRI, the effect of phlebotomy in order to lower and maintain serum ferritin below 50 µg / l on the risk of hepatocellular carcinoma (HCC) occurrence. The effect of bloodletting will be jointly evaluated on 1) episodes of hepatic decompensation, 2) non HCC liver-related mortality 3) changes in HIO during follow-up.
Read the detailed description
Purpose
The role of iron in liver carcinogenesis is supported by human, animal and cellular models through direct and indirect mechanisms. The accumulation of iron promotes liver cell proliferation and is responsible for direct structural damage or mutations of DNA caused by free iron itself or reactive oxygen species generated by its accumulation in the liver.
The influence of hepatic iron overload (HIO) on the risk of hepatocellular carcinoma (HCC) is well established in patients with genetic hemochromatosis or HCC developed on non-cirrhotic liver. However, the influence of HIO on the risk of occurrence of HCC in other chronic liver disease (including alcoholic and viral C) has been controversial. Recently, a prospective study including a large population of patients with cirrhosis (n = 301) classified according to the aetiology of liver disease (alcohol, n = 162 or hepatitis C virus (HCV)infection, n = 139) has shown the association between HIO and the occurrence of HCC in patients with alcoholic cirrhosis. Thus, the assessment of liver iron in routine clinical practice could allow the identification of patients at higher risk of developing HCC and in whom preventive measures such as iron depletion by phlebotomy could be undertaken. Based on the model of genetic hemochromatosis in which its effectiveness on survival improvement and even regression of hepatic injury has been shown, its effectiveness on the prognosis and prevention of HCC occurrence in patients with alcoholic cirrhosis must now be studied in prospective multicentre randomized trials.
The main objective of the study is to assess in patients with compensated alcoholic cirrhosis and HIO, as assessed by MRI, the effect of phlebotomy in order to lower and maintain serum ferritin below 50 µg / l on the risk of HCC occurrence. The effect of bloodletting will be jointly evaluated on 1) episodes of hepatic decompensation, 2) non HCC liver-related mortality 3) changes in HIO during follow-up.
Study Type: Interventional Study Design: Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
- Conditions
- Alcoholic Cirrhosis, Iron Overload
- Being tested
- phlebotomy
- Medical subject headings
- Liver Cirrhosis, Alcoholic, Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phlebotomyProcedure or surgery
Also called Bloodletting, Iron depletion
Procedure: Phlebotomy of 4 ml / kg to obtain (1 phlebotomy every 14 days) and maintain (1 phlebotomy every 3 months) a serum ferritin below 50 µg / l.
| Study group | Role | What they receive |
|---|---|---|
| phlebotomy | Experimental | Not described Receives: Procedure: phlebotomy |
| control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of HepatoCellular Carcinoma during follow-up
the cumulative incidence of HCC will be estimated considering death prior to the event of interest as competing risk outcomes
Measured: 3 years
Secondary outcomes (3)
Number of hepatic decompensation episodes in study participants
Measured: 3 years
Cumulative incidence of death non related to hepatoCellular Carcinoma
Measured: 3 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2014
- Study completionJun 2014
Why it stopped: delayed recruitment as compared to that expected
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcoholic 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre NAHON, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01342705
- Sponsor's protocol ID
- P091107
- Acronym
- CIRROX
- Status last verified
- Nov 2012
- First submitted
- 14 Apr 2011
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Iron Depletion by Phlebotomy on the Risk of Hepatocellular Carcinoma Occurrence in Patients With Compensated Alcoholic Cirrhosis. Prospective, Multicentre, Randomized Trial
- ClinicalTrials.gov ID
- NCT01342705
- Acronym / sponsor ID
- CIRROX / P091107
- Conditions
- Alcoholic Cirrhosis, Iron Overload
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: delayed recruitment as compared to that expected
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 27 Apr 2011 (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.
The main objective of the study is to assess in patients with compensated alcoholic cirrhosis and hepatic iron overload (HIO), as assessed by MRI, the effect of phlebotomy in order to lower and maintain serum ferritin below 50 µg / l on the risk of hepatocellular carcinoma (HCC) occurrence. The effect of bloodletting will be jointly evaluated on 1) episodes of hepatic decompensation, 2) non HCC liver-related mortality 3) changes in HIO during follow-up.
Detailed description
Purpose
The role of iron in liver carcinogenesis is supported by human, animal and cellular models through direct and indirect mechanisms. The accumulation of iron promotes liver cell proliferation and is responsible for direct structural damage or mutations of DNA caused by free iron itself or reactive oxygen species generated by its accumulation in the liver.
The influence of hepatic iron overload (HIO) on the risk of hepatocellular carcinoma (HCC) is well established in patients with genetic hemochromatosis or HCC developed on non-cirrhotic liver. However, the influence of HIO on the risk of occurrence of HCC in other chronic liver disease (including alcoholic and viral C) has been controversial. Recently, a prospective study including a large population of patients with cirrhosis (n = 301) classified according to the aetiology of liver disease (alcohol, n = 162 or hepatitis C virus (HCV)infection, n = 139) has shown the association between HIO and the occurrence of HCC in patients with alcoholic cirrhosis. Thus, the assessment of liver iron in routine clinical practice could allow the identification of patients at higher risk of developing HCC and in whom preventive measures such as iron depletion by phlebotomy could be undertaken. Based on the model of genetic hemochromatosis in which its effectiveness on survival improvement and even regression of hepatic injury has been shown, its effectiveness on the prognosis and prevention of HCC occurrence in patients with alcoholic cirrhosis must now be studied in prospective multicentre randomized trials.
The main objective of the study is to assess in patients with compensated alcoholic cirrhosis and HIO, as assessed by MRI, the effect of phlebotomy in order to lower and maintain serum ferritin below 50 µg / l on the risk of HCC occurrence. The effect of bloodletting will be jointly evaluated on 1) episodes of hepatic decompensation, 2) non HCC liver-related mortality 3) changes in HIO during follow-up.
Study Type: Interventional Study Design: Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| phlebotomy | Experimental | Procedure: phlebotomy |
| control | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age over 18
- Biopsy-proven alcoholic cirrhosis
- No previous HCC (treated or not)
- Excessive alcohol consumption, defined by more than 21 glasses weekly in women and more than 28 glasses weekly in men for at least 10 years, and considered as the main cause for liver cirrhosis
- Signed written informed consent
Key exclusion criteria (13 listed)
- Subjects deprived of their liberty by judicial or administrative decision
- Pregnant women
- Serious associated short-term life threatening disease (except HIV viral co-infection, or the liver disease itself)
- Impossibility of monitoring, whatever the reason.
- Contraindication of phlebotomy
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 |
|---|---|---|
| phlebotomyAlso: Bloodletting, Iron depletionProcedure: Phlebotomy of 4 ml / kg to obtain (1 phlebotomy every 14 days) and maintain (1 phlebotomy every 3 months) a serum ferritin below 50 µg / l. | Procedure or surgery | phlebotomy |
Primary outcome
Cumulative incidence of HepatoCellular Carcinoma during follow-up
Time frame: 3 years
the cumulative incidence of HCC will be estimated considering death prior to the event of interest as competing risk outcomes
3 secondary outcomes
Number of hepatic decompensation episodes in study participants
Time frame: 3 years
Cumulative incidence of death non related to hepatoCellular Carcinoma
Time frame: 3 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 3 years
Results and safety
The study was stopped early (reason given: delayed recruitment as compared to that expected). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
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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.
Pierre NAHON, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing phlebotomy in people with Alcoholic Cirrhosis and Iron Overload, run by Assistance Publique - Hôpitaux de Paris at 14 sites 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 6 inclusion and 13 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: stopped early, as of the sponsor's last update on 21 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites 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?
The study was stopped early (reason given: delayed recruitment as compared to that expected). 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?
Cumulative incidence of HepatoCellular Carcinoma during follow-up (time frame: 3 years). 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 21 Apr 2015.