Efficacy of PTX+IFN Alpha+ RBV on Hepatitis C Virus Coinfected HIV Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by Centro Universitario de Ciencias de la Salud, Mexico
Sponsor:
Information provided by (Responsible Party):
JAIME ANDRADE VILLANUEVA, Centro Universitario de Ciencias de la Salud, Mexico
ClinicalTrials.gov Identifier:
NCT02008214
First received: December 3, 2013
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

Current Hepatitis C virus (HCV) treatment consists of the combination of interferon alpha 2a (IFN-alpha 2a) plus ribavirin (RBV) and it provides sustained virologic responses (SVR) on 54 to 56% on HCV monoinfected patients and this response is even lower on HIV-HCV coinfected patients. A previous study on HCV monoinfected patients showed that the addition of pentoxyfylline (PTX) to a treatment scheme based on interferon-alfa and ribavirin increased SVR on 25%, although it is not known if the same effect is to be obtained in HCV-HIV coinfected patients.

On the other hand, other factors such as host genetics, have proved to influence treatment response on HCV infected patients. The best described genetic factor so far is the interleukin 28B (IL28B) polymorphism rs12979860, where a cytosine-cytosine (CC) genotype provides an almost twice increase on SVR than the rest of the genotypes.

Therefore, this is a randomized, double blind study to assess the efficacy of pentoxyfylline addition to a treatment scheme based on interferon-alfa and ribavirin in chronic HCV genotype 1, co-infected HIV-1 positive subjects, considering the IL28B polymorphism rs12979860.

HIV-HCV coinfected subjects currently receiving Highly active antiretroviral therapy (HAART), with at least 8 months on undetectable HIV viral load and T helper cells count of 200 or higher will be included. Patients will be randomized on one of two groups:

  • Group A: IFN alpha 2a + RBV + PTX
  • Group B: IFN alpha 2a + RBV + placebo

Patients will be followed for primary outcome during 72 (for rapid responders) or 96 weeks (for non rapid responses). Outcome measures will be the following:

  • SVR rate 24 weeks after the end of treatment
  • Grade of Hepatic fibrosis from baseline to the end of treatment, measured by transient elastography and the AST to platelet ratio index (APRI index)
  • IL28B rs12979860 genotype

The study hypothesis is that the addition of PTX to a treatment scheme based on IFN-alfa2a and RBV in chronic HCV genotype 1, co-infected HIV-1 positive subjects will improve SVR rate and fibrosis progression irrespectively of IL28B rs12979860 genotype.


Condition Intervention Phase
Hepacivirus
HIV Infections
Drug: Pentoxifylline
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Pentoxyfylline Addition to a Treatment Scheme Based on Interferon Alpha and Ribavirin on Hepatitis C Virus Coinfected HIV Patients, Considering Interleukin 28B Polymorphism rs12979860

Resource links provided by NLM:


Further study details as provided by Centro Universitario de Ciencias de la Salud, Mexico:

Primary Outcome Measures:
  • sustained virologic rate 24 weeks post treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection [ Time Frame: SVR rate at 24 weeks after the end of therapy ] [ Designated as safety issue: No ]
    Primary objective: is to evaluate sustained virologic response at post treatment week 24 following treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection


Secondary Outcome Measures:
  • grade of hepatic fibrosis [ Time Frame: Baseline and week 72 (for quick responders) or week 96 (for non-quick responders) ] [ Designated as safety issue: No ]
    The liver stiffness (hepatic fibrosis) will be measured by transient elastography and the APRI index on the baseline visit and then at the follow up visit after treatment, which will be after 72 weeks, for patients that turn out to be quick responders; or 96 weeks, for patients that turn out to be non-quick responders.

  • rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates [ Time Frame: RVR at week 4 and eRVR at week 48 post treatment ] [ Designated as safety issue: No ]
    secondary objective (2): Evaluate rapid virologic response (RVR) and extended rapid virologic response (eRVR)


Other Outcome Measures:
  • Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism [ Time Frame: week 72 ] [ Designated as safety issue: No ]
    We will compare the percentage of patients with CC genotype among patients that achieved sustained virologic response and those who did not achieved it. This is to confirm if the intervention provides a beneficial effect, irrespectively of host genetic factors.


Estimated Enrollment: 60
Study Start Date: December 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PTX
IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral PTX 400 mg each 12 h, oral
Drug: Pentoxifylline
Addition of pentoxifylline to current HCV treatment
Placebo Comparator: Placebo
IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral Placebo oral daily
Drug: Placebo
Placebo matching pentoxifylline dosage

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV/HCV coinfected patients
  • 18 to 65 years old
  • currently receiving HAART
  • non-pregnant women
  • HIV infection controlled as: undetectable viral load (<40 copies/mL) for at least 8 months and T helper cells count of 200 cells/μL or above
  • no contraindications to IFN alpha2a, RBV or PTX treatment
  • sign informed consent form
  • laboratory parameters within acceptable ranges

Exclusion Criteria:

  • Women that present a positive pregnancy test during the study
  • Patients that for any reason no longer wish to receive IFN alpha2a, RBV or PTX treatment
  • Serious adverse events that prevent to continue IFN alpha2a, RBV or PTX treatment; such as severe neutropenia, severe thrombocytopenia or severe anemia
  • Presence of an opportunistic infection or malignancy that requires treatment with drugs interacting with IFN alpha2a, RBV or PTX
  • Patients that fail to adhere to treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02008214

Contacts
Contact: Jaime Andrade-Villanueva, MD, MSc +52 33 36147586 andradevjav@gmail.com
Contact: Luz A Gonzalez-Hernandez, MD, PhD +52 33 36147586 luceroga08@gmail.com

Locations
Mexico
Hospital Civil de Guadalajara Not yet recruiting
Guadalajara, Jalisco, Mexico, 44280
Contact: Mara Llamas-Covarrubias, BSc, PhD    +52 33 36147586    mara.covarrubias@gmail.com   
Principal Investigator: Jaime Andrade-Villanueva, MD, MSc         
Sub-Investigator: Luz A Gonzalez-Hernandez, MD, PhD         
Sub-Investigator: Mara A Llamas-Covarrubias, BSc, PhD         
Sponsors and Collaborators
Centro Universitario de Ciencias de la Salud, Mexico
  More Information

No publications provided

Responsible Party: JAIME ANDRADE VILLANUEVA, Professor-Investigator, Centro Universitario de Ciencias de la Salud, Mexico
ClinicalTrials.gov Identifier: NCT02008214     History of Changes
Other Study ID Numbers: PTX-HCV/HIV
Study First Received: December 3, 2013
Last Updated: December 6, 2013
Health Authority: Mexico: Ethics Committee

Keywords provided by Centro Universitario de Ciencias de la Salud, Mexico:
Pentoxifylline
Sustained virologic response
Hepatic fibrosis

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Pentoxifylline
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on October 19, 2014