Phlebotomy and Risk of Hepatocellular Carcinoma in Patients With Compensated Alcoholic Cirrhosis (CIRROX)

This study has suspended participant recruitment.
(delayed recruitment as compared to that expected)
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01342705
First received: April 14, 2011
Last updated: November 19, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Alcoholic Cirrhosis
Iron Overload
Procedure: phlebotomy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Cumulative incidence of HepatoCellular Carcinoma during follow-up [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    the cumulative incidence of HCC will be estimated considering death prior to the event of interest as competing risk outcomes


Secondary Outcome Measures:
  • Number of hepatic decompensation episodes in study participants [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Cumulative incidence of death non related to hepatoCellular Carcinoma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 324
Study Start Date: May 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: phlebotomy Procedure: phlebotomy
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.
Other Names:
  • Bloodletting
  • Iron depletion
No Intervention: control

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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)

    • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01342705

Locations
France
Amiens University Hospital :
Amiens, France
Avicenne
Bobigny, France
Jean Verdier
Bondy, France, 93140
CHU Bordeaux univerity hospital 1
Bordeaux, France
CHU Bordeaux University hospital 2
Bordeaux, France
CHU
Caen, France
Antoine Béclère
Clamart, France
CHU
Grenoble, France
CHU
Lille, France
CHU
Montpellier, France
CHU
Nancy, France
CHU
Nice, France
CHU
Rennes, France
CHU
Rouen, France
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Pierre NAHON, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01342705     History of Changes
Other Study ID Numbers: P091107
Study First Received: April 14, 2011
Last Updated: November 19, 2012
Health Authority: France: Ministry of Health

Additional relevant MeSH terms:
Carcinoma
Liver Cirrhosis
Fibrosis
Liver Cirrhosis, Alcoholic
Iron Overload
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Diseases
Digestive System Diseases
Pathologic Processes
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Iron Metabolism Disorders
Metabolic Diseases
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on April 15, 2014