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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02008214
• Other study ID #: PTX-HCV/HIV
• Status: Not yet recruiting
• Phase: Phase 4
• First received: December 3, 2013
• Last updated: December 6, 2013
• Start date: December 2013
• Est. completion date: March 2016

Study information

• Verified date: December 2013
• Source: Centro Universitario de Ciencias de la Salud, Mexico
• Contact: Jaime Andrade-Villanueva, MD, MSc
• Phone: +52 33 36147586
• Email: andradevjav[@]gmail.com
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: March 2016
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepacivirus
• Hepatitis C
• HIV Infections

Intervention

Drug:
• Pentoxifylline
Addition of pentoxifylline to current HCV treatment
• Placebo
Placebo matching pentoxifylline dosage

Locations

Country	Name	City	State
Mexico	Hospital Civil de Guadalajara	Guadalajara	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
Centro Universitario de Ciencias de la Salud, Mexico

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism	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.	week 72	No
Primary	sustained virologic rate 24 weeks post treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection	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	SVR rate at 24 weeks after the end of therapy	No
Secondary	grade of hepatic fibrosis	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.	Baseline and week 72 (for quick responders) or week 96 (for non-quick responders)	No
Secondary	rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates	secondary objective (2): Evaluate rapid virologic response (RVR) and extended rapid virologic response (eRVR)	RVR at week 4 and eRVR at week 48 post treatment	No