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

NCT02008214 | Unknown Phase 4

• 1 other identifier: PTX-HCV/HIV
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepacivirus; HIV Infections

Keywords

Pentoxifylline; Sustained virologic response; Hepatic fibrosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• grade of hepatic fibrosis

  Baseline and week 72 (for quick responders) or week 96 (for non-quick responders)

• rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates

  RVR at week 4 and eRVR at week 48 post treatment

Other Outcomes (1)

• Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism

  week 72

Study Arms (2)

PTX

EXPERIMENTAL

IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral PTX 400 mg each 12 h, oral

Drug: Pentoxifylline

Placebo

PLACEBO COMPARATOR

IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral Placebo oral daily

Drug: Placebo

Interventions

Pentoxifylline DRUG

Addition of pentoxifylline to current HCV treatment

PTX

Placebo DRUG

Placebo matching pentoxifylline dosage

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV/HCV coinfected patients
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro Universitario de Ciencias de la Salud, Mexico: lead

Study Sites (1)

Hospital Civil de Guadalajara

Guadalajara, Jalisco, 44280, Mexico

Location

MeSH Terms

Conditions

HIV Infections; Liver Cirrhosis

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Jaime Andrade-Villanueva, MD, MSc

CONTACT

+52 33 36147586; andradevjav@gmail.com

Luz A Gonzalez-Hernandez, MD, PhD

CONTACT

+52 33 36147586; luceroga08@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor-Investigator

Study Record Dates

• First Submitted: December 3, 2013
• First Posted: December 11, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2016
• Last Updated: December 11, 2013

Record last verified: 2013-12

Locations

ME (1)