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Trial record 48 of 396 for:    IFNA2 AND RBV AND sustained

Randomized Controlled Open Label Trial of Peg Alpha 2a Interferon and Adjusted-dose of Ribavirin vs. Standard Therapy in the Treatment of Naive Chronic Hepatitis C Patients Infected With Genotype 4

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01686789
Recruitment Status : Completed
First Posted : September 18, 2012
Last Update Posted : February 24, 2016
Information provided by (Responsible Party):
Faisal M Sanai, King Abdulaziz Medical City

Brief Summary:
The study aims to study the outcome of pharmacokinetics-adjusted dose ribavirin (plus pegIFN) on the SVR in chronic HCV patients.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Virus Drug: Pegylated interferon alpha-2a Phase 4

Detailed Description:

Background: The introduction of Peg interferon and Ribavirin (an oral nucleoside analogue) for chronic Hepatitis C has led to the concept that chronic hepatitis C (HCV) is a curable disease. Improvement of treatment efficacy is still a major challenge. Optimal Ribavirin doses are essential to achieve SVR (sustained virological response). A recent trial showed significantly higher sustained virological response (SVR) in patients receiving 15.2 mg/kg/day of Ribavirin compared with 13.3 mg/kg/day. Ribavirin was given in combination with Peg interferon alpha-2b (1). A small pilot study, in which 10 patients with Chronic Hepatitis C genotype 1 were treated with Ribavirin dosage up to 3600 mg/day- mean of 2540 mg/day- plus Peg-interferon alpha-2a, achieving a target concentration of Ribavirin >15 micromol before W 12, led to 90% of SVR(2). All patients managed to complete the one year treatment period but all needed EPO and two were transfused.

Patient's global exposure to Ribavirin as evaluated by the area under the curve (AUC) seems more pertinent in terms of exposure-effect relationship than measuring Ribavirin level at any single time point. A recent study showed in HCV patients infected with genotype 1 that Ribavirin plasma exposure after the first dose (i.e., interdose AUC0-12h or abbreviated AUC0-4h) was significantly and strongly linked with SVR, whereas AUCs determined at W12 and W24 and trough concentrations at Day 0 and W12 were not (3).

Therefore, we propose a randomized controlled trial to investigate whether adjusted Ribavirin doses based on AUC0-4h obtained at D-7 after 600mg dose of Ribavirin versus fixed standard doses can improve outcome in treatment of chronic hepatitis C naïve patients infected with genotype 4.

Methodology: After AUC0-4h has been determined at D-7 (7 days before randomization) for 190 genotype 4 patients recruited into the trial, the patients are randomized into two groups: Group A: to receive standard dose of Ribavirin 1000-1200 mg/day) and Group B: to receive adjusted-dose of Ribavirin according to AUC0-4h. The individual calculated dose should be administered for each patient beginning on the first day of treatment. Both groups will receive combination treatment with peginterferon alpha 2a 180 mcg/week for a total of 48 weeks.

Both treatment groups will receive Darbepoetin if subsequent Hb is < 11 g/dl for males and females. Our main inclusion criteria will be: patients 18-70 years old with serological evidence of chronic hepatitis C and positive HCV RNA of genotype 4, with a liver biopsy within 3 years prior to recruitment. Our main exclusion criteria will be: decompensated cirrhotic patients, HBV/HIV co-infection, evidence of hepatocellular carcinoma (HCC), significant evolutive cardiovascular, pulmonary, renal or psychiatric disease, pregnancy/breast feeding or patients post liver transplantation and anemia.

Our primary outcome will be: HCV-RNA negativity 24 weeks after the end of treatment (SVR) (input adjusted dose on SVR). Our secondary outcome will be: rapid virological response (RVR), early virological response (EVR), partial early virological response (pEVR), end of treatment response (ETR), relapse after (ETR), biochemical response and safety and tolerability of high doses of Ribavirin.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Controlled Open Label Trial of Peg Alpha 2a Interferon and Adjusted-dose of Ribavirin vs. Standard Therapy in the Treatment of Naive Chronic Hepatitis C Patients Infected With Genotype 4
Study Start Date : January 2011
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Arm Intervention/treatment
Active Comparator: Pegylated interferon alpha-2a plus standard dose ribavirin
Pegylated interferon alpha-2a 180 mcg weekly plus standard dose ribavirin 100-1200 mg/day for 48 weeks
Drug: Pegylated interferon alpha-2a
Experimental: Pegylated interferon alpha-2a 180 mcgs adjusted dose ribavirin
Pegylated interferon alpha-2a 180 mcg weekly plus adjusted dose ribavirin for 48 weeks
Drug: Pegylated interferon alpha-2a

Primary Outcome Measures :
  1. Sustained virological response [ Time Frame: 72 weeks ]
    Detectability of HCV RNA after 24 weeks of treatment completion by a realTime PCR-based technique

Secondary Outcome Measures :
  1. Requirement of blood-related products [ Time Frame: 48 weeks ]
    The development of anemia or requirement of blood-related products

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 18-70 years of age
  2. Chronic hepatitis C documented by a detectable HCV RNA level by a PCR performed within 3 months -A liver biopsy performed within 3 years or fibro test/fibroscan within 1 year of inclusion.
  3. Naive patients
  4. Genotype 4
  5. Compensated cirrhosis hepatitis C liver disease (Child-Pugh ≤ 6)
  6. Patient needing, according to the physician, the initiation of a combined therapy of pegylated interferon alfa plus Ribavirin
  7. Negative HBsAg test and HIV-Elisa test
  8. Negative pregnancy test at baseline in women in age of procreation
  9. Efficient contraception all along the treatment period, and for 6 months after discontinuation of the treatment for women and men

Exclusion Criteria:

  1. Decompensated Cirrhotic patients
  2. HBV or HIV co-infection
  3. Evidence of hepatocellular carcinoma
  4. Significant and evolutive cardiovascular, pulmonary, severe psychiatric disorder or renal dysfunction (calculated creatinine CL < 50 ml/min) *. Patients who met the trial criteria if subsequent calculated creatinine CL < 50 ml/min may need ribavirin dose reduction.
  5. Non compensated thyroid dysfunction
  6. Recent history of epilepsy (less than 6 months)
  7. Absolute contraindications to one of the drug of combination therapy
  8. Any non-compensated cardiac disease including ischemic heart disease Chronic cardiac failure (grade III or IV - NYHA classification)
  9. Uncontrolled high blood pressure (SBP > 180 mmHg during inclusion in spite of hypertension treatment)
  10. Pregnancy or breast feeding.
  11. Post liver transplantation patient with HCV
  12. Alcohol or drug induced liver disease.
  13. Metabolic or autoimmune liver disease.
  14. Hemoglobinopathies or anemia; hemoglobin <12 gm /dl for females and <12.5 for males not corrected by erythropoietin
  15. Neutropenia (<1500/mm³)
  16. Thrombocytopenia (<90,000/mm3), thrombocytosis (> 500,000/mm3)
  17. Patients with evolutive diabetic or hypertensive retinopathy. Patients who are stable can be included but should be regularly followed during treatment.
  18. Hypersensitivity to epoetin beta or one of its excipients
  19. Previous history or increased risk of venous thrombosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01686789

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Saudi Arabia
King Faisal Specialist Hospital & Research Centre
Riyadh, Saudi Arabia, 11159
King Abdulaziz Medical City
Riyadh, Saudi Arabia, 11462
King Khaled University Hospital
Riyadh, Saudi Arabia
Sponsors and Collaborators
King Abdulaziz Medical City

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Responsible Party: Faisal M Sanai, Consultant Hepatologist & Liver Transplant Physician, King Abdulaziz Medical City Identifier: NCT01686789     History of Changes
Other Study ID Numbers: RC08-064
First Posted: September 18, 2012    Key Record Dates
Last Update Posted: February 24, 2016
Last Verified: February 2016
Additional relevant MeSH terms:
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Interferon alpha-2
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Peginterferon alfa-2a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs