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

This study is currently recruiting participants.
Verified September 2012 by King Abdulaziz Medical City
Sponsor:
Information provided by (Responsible Party):
Faisal M Sanai, King Abdulaziz Medical City
ClinicalTrials.gov Identifier:
NCT01686789
First received: September 13, 2012
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by King Abdulaziz Medical City:

Primary Outcome Measures:
  • Sustained virological response [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
    Detectability of HCV RNA after 24 weeks of treatment completion by a realTime PCR-based technique


Secondary Outcome Measures:
  • Requirement of blood-related products [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    The development of anemia or requirement of blood-related products


Estimated Enrollment: 190
Study Start Date: January 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01686789

Contacts
Contact: Ibrahim Altraif, MD 966505482149 ibrahimtraif@yahoo.com

Locations
Saudi Arabia
King Abdulaziz Medical City Recruiting
Riyadh, Saudi Arabia, 11462
Contact: Ibrahim Altraif, MD    8011111    ibrahimtraif@yahoo.com   
Principal Investigator: Ibrahim Altraif, MD         
King Faisal Specialist Hospital & Research Centre Recruiting
Riyadh, Saudi Arabia, 11159
Contact: Hamad Alashgar, MD       alashgar@kfshrc.edu.sa   
Principal Investigator: Hassan Aleid, MD         
King Khaled University Hospital Recruiting
Riyadh, Saudi Arabia
Contact: Ayman Abdo, FRCPC       aabdo@ksu.edu.sa   
Principal Investigator: Ayman Abdo, FRCPC         
Sponsors and Collaborators
King Abdulaziz Medical City
  More Information

No publications provided

Responsible Party: Faisal M Sanai, Consultant Hepatologist & Liver Transplant Physician, King Abdulaziz Medical City
ClinicalTrials.gov Identifier: NCT01686789     History of Changes
Other Study ID Numbers: RC08-064
Study First Received: September 13, 2012
Last Updated: September 18, 2012
Health Authority: Saudi Arabia: Ethics Committee
King Abdallah International Medical Research Centre, National Guard Health Affairs, Riyadh, Saudi Arabia:

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014