High-dose Ribavirin in Treatment of Chronic Hepatitis C Genotype 1 or 4

• Status: Terminated
• Trial end date: 2013-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Optimal ribavirin dosages are essential in achieving SVR (sustained virological response). Several studies have shown higher SVR rates in patients receiving higher doses of ribavirin. Therefore we propose a randomized controlled open label multicenter trial to investigate wether high (25-29mg/kg) dose ribavirin can improve outcome in patients in infected with hepatitis C virus genotype 1 or 4 compared to standard dose (12-15mg/kg).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Foundation for Liver Research
• Collaborator: Hoffmann-La Roche
• Treatments: Interferon-alpha; Peginterferon alfa-2a; Ribavirin

Criteria

Inclusion Criteria:

• hepatitis C genotype 1 or 4

• high viral load (>400000 IU/ml)

• indication for antiviral treatment or patient's desire for antiviral treatment

• hepatitis C treatment naive

• liver biopsy within 3 years of screening visit or when biopsy is contraindicated e.g in patients with clotting diseases or when a patient refuses to undergo a new biopsy in case the liver biopsy is older than 3 years, substitution by fibroscan is allowed.

• age 18-70 years

Exclusion Criteria:

• serum bilirubin >35 μmol/l

• albumin <36 g/l

• prothrombin time >4 sec prolonged

• platelets <90x109/l

• decompensated cirrhosis (Child-Pugh Grade B or C)

• hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma (hepatic imaging should be performed within 3 months prior to screening for cirrhotic patients and within 6 months prior to screening for non-cirrhotic patients)

• alcoholic liver disease (indicator: MCV>100)

• obesity induced liver disease (indicators: steatosis proven by biopsy or ultrasound in association with a body mass index >30)

• drug related liver disease (indicator: positive history of hepatic toxic drug intake with a causal relation)

• auto-immune hepatitis (indicators: IgG >30g/l, anti smooth-muscle or antinuclear antibodies titer ³1:40)

• hemochromatosis (indicator: ferritin >1000 μg/l)

• Wilson's disease (indicator: ceruloplasmin (<0.2 g/l)

• alpha-1 antitrypsin deficiency (indicator alpha-1 antitrypsin <0.8 g/L)

• co-infection with hepatitis B virus or human immunodeficiency virus (HIV)

• any cardiovascular dysfunction (e.g. cardiac decompensation, myocardial infarction, present or history of arrythmia)

• other medical illness that might interfere with this study: significant pulmonary or renal dysfunction, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g.: steroid therapy, organ transplants other than cornea and hair transplant)

• contra-indications for peginterferon and/or ribavirin:

• severe psychiatric disorder, such as major psychoses, suicidal ideation, suicidal attempt and/or manifest depression. Severe depression would include the following: (a) subjects who have been hospitalized for depression, (b) subjects who have received electroconvulsive therapy for depression, or (c) subjects whose depression has resulted in a prolonged absence of work and/or significant disruption of daily functions. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject's mental status supports that the subject is clinically stable and that there is ongoing evaluation of the patient's mental status during the study

• visual symptoms related to retinal abnormalities

• pregnancy, breast-feeding or inadequate contraception

• thalassemia, spherocytosis

• females who are pregnant or intending to become pregnant or male partners of females who are pregnant or intending to become pregnant

• absolute neutrophil count (ANC) <1.40x109/l

• hemoglobin (Hb) <7.5 mmol/l (female) or <8.1 mmol/l (male)

• serum creatinine concentration >1.5 times the upper limit of normal at screening

• substance abuse, such as I.V. drugs or alcohol (indicator: >28 drinks/week). If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 1 year

• any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study