Efficacy of PTX+IFN Alpha+ RBV on Hepatitis C Virus Coinfected HIV Patients
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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 |
- 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
- 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)
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT02008214
| 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 |
| 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 | |
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:
|
Acquired Immunodeficiency Syndrome HIV Infections Hepatitis C Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis, Viral, Human Immune System Diseases Immunologic Deficiency Syndromes Lentivirus Infections Liver Diseases RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral |
Slow Virus Diseases Virus Diseases Pentoxifylline Antioxidants Cardiovascular Agents Enzyme Inhibitors Free Radical Scavengers Hematologic Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Phosphodiesterase Inhibitors Physiological Effects of Drugs Platelet Aggregation Inhibitors Protective Agents Radiation-Protective Agents |
ClinicalTrials.gov processed this record on February 26, 2015