Use or Non-use of Epoetin Beta in Patients Infected by Chronic Hepatitis C

Multicenter Study, Randomized and Pragmatic, Comparing Two Therapeutic Strategies : Use or Non-use of Epoetin Beta in Patients Infected by Chronic Hepatitis C and Treated by Combination Therapy Peginterferon Alfa-2a Plus Ribavirin

The purpose is to demonstrate a correction of anemia in hepatitis C virus treatment with peginterferon plus ribavirin.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: epoetin beta (NeoRecormon®)

Detailed Description

Show that the correction of anemia by epoetin beta (NeoRecormon®) able to maintain a optimal dose of ribavirin (Copegus®). The study compares two therapeutic strategies : use or non-use of epoetin beta (NeoRecormon®) in patients infected by chronic hepatitis C and treated by combination therapy Peginterferon alfa-2a (Pegasys®) plus ribavirin (Copegus®). The main judgement criteria are :

• Sustained Viral Response (Week 72)
• Viral Response at the End of Treatment (Week 48)
• Quality of life
• Cumulative dose of ribavirin from D0-W24 and from W24-W48 periods
• Clinical and biological tolerance

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Aix en Provence, France, 13616
    • H Aix en Provence
  • Angers, France, 49933
    • UH Angers
  • Avignon, France, 84 902
    • H Avignon
  • Bourgoin-Jallieu, France, 38 317
    • H Bourgoin-Jallieu
  • Brest, France, 29 609
    • UH BREST
  • Caen, France, 14 033
    • UH Caen
  • Châteauroux, France, 36 000
    • H Chateauroux
  • Clermont Ferrand, France, 63009
    • UH Clermont Ferrand
  • Corbeil-Essonnes, France, 91 106
    • H Corbeil-Essonnes
  • Creil, France, 60 100
    • H Creil
  • Créteil, France, 94010
    • H Créteil
  • Dijon, France, 21 079
    • UH Dijon
  • Dreux, France, 28100
    • H Dreux
  • Freyming-Merlebach, France, 57 804
    • H Freyming-Merlebach
  • Grasse, France, 06 130
    • H Grasse
  • Grenoble, France, 38 043
    • UH Grenoble
  • La Roche sur Yon, France, 85925
    • H La Roche sur Yon
  • Le Mans, France, 72000
    • H le Mans
  • Limoges, France, 87042
    • UH Limoges
  • Lyon, France, 69 288
    • UH Lyon
  • Marseille, France, 13 285
    • H Saint-Joseph
  • Montauban, France, 82 013
    • H Montauban
  • Montpellier, France, 34 295
    • UH Montpellier
  • Montélimar, France, 26 200
    • H montélimar
  • Nantes, France, 44 800
    • UH Nantes
  • Orléans, France, 45100
    • H Orléans
  • Paris, France, 75 020
    • H Tenon
  • Paris, France, 75 571
    • H saint-Antoine
  • Pau, France, 64 011
    • H Pau
  • Poitiers, France, 86 020
    • UH Poitiers
  • Rennes, France, 35 043
    • UH Rennes
  • Rouen, France, 76 031
    • UH Rouen
  • Saint Laurent du Var, France, 06721
    • Arnault Tzanck Institute
  • Saint-Dizier, France, 52 115
    • H Saint-Dizier
  • Toulouse, France, 31 059
    • UH Toulouse
  • Tourcoing, France, 59 208
    • H Tourcoing
  • Tours, France, 37 170
    • UH Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients 18 years old or above
• Patient with French social security or other equivalent health assurance
• Patient with informed consent
• Serologic evidence of chronic hepatitis C by detectable anti-HCV antibodies
• Patient infected by HCV genotype 1, 4, 5 or 6
• Compensated liver disease (Child-Pugh ≤ 6)
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior the enrollment in the study
• All fertile males and females receiving ribavirin must have effective contraception during treatment and during the 6 following months
• Patient naive of treatment with installation of treatment by investigator following criteria for use Peginterferon alfa-2a (Pegasys) and ribavirin (Copegus)

Exclusion Criteria:

• Women with ongoing pregnancy or breast feeding
• Male partner of pregnancy woman
• Minor
• Major protected by French law for biomedical study
• Co-infection by HBV or HIV
• History or other evidence of decompensated liver disease or Child-Pugh score > 6
• Clinical or radiological evidence (abdominal ultrasound, CT scan or MRI) of hepatocellular carcinoma
• IFN or ribavirin at any previous time
• Patient who received an erythropoetin within 2 months before inclusion
• History of epilepsy (during the last 6 months)
• Chronic cardiac insufficiency (stage III or IV in classification from the New York Heart Association [NYHA])
• Not controlled portal hypertension
• Antecedents or risk of venous thrombosis
• Surgery within 3 months before inclusion
• Serum creatinine level >15 mg/mL (130µmol/L)
• Deficiency in vitamin B9 and/or B12 (suspected with macrocytosis > 105 µm3)
• Thrombocytosis (platelets > 500 000/mm3)
• Chronic inflammatory syndrome (CRP > 10 mg/L)
• Deficiency not corrected in iron :
• Ferritin blood level < 10 µg/L Or - Transferrin saturation coefficient < 20 %
• History of neoplasia (except basocellular epithelioma and cervical cancer)
• Contraindications to use epoetin beta or an excipient from molecule to study (urea, polysorbate 20, glycine, leucine, isoleucine, threonine, glutamic acid, phenylalanine, benzoic acid, benzyl alcohol)
• Absence of written informed consent
• Exclusion time for another biomedical study
• Patient with blood concentration of hemoglobin lower or equal to 12 g/dL for male or lower or equal to 11 g/dL for female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group A; HCV treatment with peginterferon plus ribavirin during 48 weeks
Active Comparator: Groupb; HCV treatment with peginterferon plus ribavirin during 48 weeks plus epoetin beta under anemia conditions	Drug: epoetin beta (NeoRecormon®); • Prescription of the epoetin beta : when blood concentration of hemoglobin is lower or equal to 12 g/dL in male or lower or equal to 11 g/dL in female; Other Names: NeoRecormon®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Viral Response (Week 72)	Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 24 in the Post-treatment Follow-up Period	Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Viral Response at the End of Treatment (Week 48)	Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 48	Week 48
• Quality of life	Questionnaire HQLQ; Fatigue Severity Scale HQLQ questionnaire and Fatigue Severity Scale	D0, W4, W12, W24, W48, W72
• Cumulative dose of ribavirin from D0-W24 and from W24-W48 periods	• Cumulating dose of ribavirin during following periods D0-W24 and W24-W48	D0, W4, W8, W12, W16, W20, W24, W28, W32, W36, W40, W44, W48
• Clinical and biological tolerance	Up to 72 weeks, includes all serious and other adverse events that newly occurred or worsened after treatment with PegIFNα-2a, ribavirin or epoetin beta	D0, W4, W8, W12, W16, W20, W24, W28, W32, W36, W40, W44, W48, W52, W60, W72

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Principal Investigator: Françoise Lunel-Fabiani, MD, PhD, UH Angers

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: December 5, 2005
• First Submitted That Met QC Criteria: December 5, 2005
• First Posted (Estimate): December 6, 2005

Study Record Updates

• Last Update Posted (Estimate): December 12, 2014
• Last Update Submitted That Met QC Criteria: December 11, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: ribavirin; Chronic hepatitis C; peginterferon; epoetin beta
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Hematinics; Epoetin Alfa
• Other Study ID Numbers: CP 2005-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No