Clinical trial NCT02247440: HCV-HIV Co-infected Patient Cohort in Thailand
Official title: Response to Peg-interferon and Ribavirin for the Treatment of HCV Infection in HIV Co-infected Patients, Implemented in Public Hospitals in Thailand
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C Infection
HIV
Keywords: HCV
HIV
Thailand
pegylated interferon
ribavirin
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, Thailand
First posted: 2014-09-25
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study of HCV treatment using the standard regimen of pegylated-interferon plus ribavirin in HIV co-infected patients participating in the PHPT cohort study. The treatment will be implemented in conjunction with gastro-enterologists/hepatologists by internists responsible for the participant's HIV treatment.

Chronic hepatitis C virus (HCV) infection is responsible for several severe and life threatening complications, which are worsened by HIV co-infection. HIV-HCV co-infected patients are at a higher risk of death compared to HIV mono-infected individuals, even if HIV replication is suppressed on antiretroviral treatment.

The goal of HCV antiviral treatment is to cure HCV infection. Curing HCV infection allows fibrosis regression, improved clinical outcomes. In addition, individuals who have been cured are no longer contagious to other individuals, therefore widespread access to HCV treatment may contribute to the control of the HCV epidemic.

A combination of injectable pegylated-interferon with oral ribavirin is currently the recommended regimen for the treatment of hepatitis C in the setting of HIV co-infection. They are administered for 24 weeks in HCV mono-infected patients but need to be administered for one year in HIV-HCV co-infected patients. Newer drugs, such as the first generation HCV protease inhibitors (boceprevir, telaprevir), administered concomitantly, are used in patients who have not been cured using peg-interferon + ribavirin, and may allow for shorter treatment.

PRIMARY OBJECTIVE

1. To determine the percentage of patients according to genotypes with sustained virological response 6 months after treatment discontinuation (SVR).

HCV TREATMENT

* Peg-interferon alpha 2-b (a subcutaneous injection of 1.5 micrograms/kg once a week)
* Ribavirin dosing according to HCV genotype and body weight; dose adjustment in case of anemia.

A total of 60 patients could be enrolled in the study: 15 HCV-HIV co-infected patients in a first part (starting in August 2014) and 45 patients in a second part, depending on funding.

Detailed description: Study Population Screening: HIV infected patients with a positive anti-HCV test will be approached for screening if they are at least 18 years old, participate in the PHPT cohort study, have evidence of control of HIV replication and have a CD4 cell count ≥200 cells/mm3 if currently receiving antiretroviral HIV treatment (on the same anti-HIV regimen for at least 12 weeks); or HIV RNA load ≤5000 copies/ml CD4 cells ≥500 cells/mm3if not receiving antiretroviral treatment.

Inclusion Criteria

* Evidence of chronic HCV infection for at least 6 months before study entry (at least one detectable HCV viral load, i.e. ≥17 IU/mL, with an antibody test positive at least 6 months before the HCV RNA load result)
* Fibrosis Stage F2-3-4 determined by transient elastography (Fibroscan or other similar equipment). During the first part of the study, priority will be given to patients with Fibrosis Stage F2-3.
* Negative pregnancy test (on the day of inclusion). Main exclusion criteria
* Anemia and thrombocytopenia
* Severe liver damage, advanced stage cirrhosis or cancer
* Uncontrolled diabetes, Uncontrolled thyroid dysfunction
* Retinopathy
* Creatinine clearance \<50 mL/min (Cockcroft)
* Disease associated with the immune system
* Significant heart problems
* Severe neuropsychiatric conditions
* Contra-indication to study treatment (including pregnancy or lack of effective contraception in the participant or female partner)
* Other exclusion criteria related to the use of ribavirin and peg-interferon
* Any conditions that, in the investigator's judgment, may compromise the follow up.

Follow up After HCV treatment initiation, patients will be monitored for safety and antiviral efficacy at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 weeks (end of treatment) and 6 months after treatment discontinuation.

Treatment will be discontinued earlier in patients who do not achieve early viral response, i.e. a decrease of at least 2 log10 HCV RNA IU/mL after the first 12 weeks of HCV therapy.

Eligibility criteria: Inclusion Criteria:

* Evidence of chronic HCV infection for at least 6 months before study entry (at least one detectable HCV viral load, i.e. ≥17 IU/mL, with an antibody test positive at least 6 months before the HCV RNA load result)
* Fibrosis Stage F2-3-4 determined by transient elastography (Fibroscan or other similar equipment). During the first part of the study, priority will be given to patients with Fibrosis Stage F2-3.
* Negative pregnancy test (on the day of inclusion).

Exclusion Criteria:

* Anemia and thrombocytopenia
* Severe liver damage, advanced stage cirrhosis or cancer
* Uncontrolled diabetes, Uncontrolled thyroid dysfunction
* Retinopathy
* Creatinine clearance \<50 mL/min (Cockcroft)
* Disease associated with the immune system
* Significant heart problems
* Severe neuropsychiatric conditions Contra-indication to study treatment (including pregnancy or lack of effective contraception in the participant or female partner)
* Other exclusion criteria related to the use of ribavirin and peg-interferon
* Any conditions that, in the investigator's judgment, may compromise the follow up.

Primary outcomes:
measure: Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation
timeFrame: 6 months after end of treatment, i.e. 1.5 years after treatment initiation
Secondary outcomes:
measure: Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin)
timeFrame: From initiation of treatment to 6 months after treatment discontinuation
measure: Number of Participants Grouped by HIV-1 RNA Concentrations
timeFrame: At time of treatment discontinuation (whatever its date) and 6 months thereafter
Other outcomes:
measure: Number of Participants Completed the First 24 and 48 Weeks of Treatment
timeFrame: From initiation of treatment to the first 48 weeks of treatment
measure: Number of Adverse Events by Severity Grade
timeFrame: From initiation of treatment to 6 months after treatment discontinuation
measure: Number of Participants Able to Perform Self-injections of Peg-interferon
timeFrame: From initiation of treatment to the first 48 weeks of treatment
measure: Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80%
timeFrame: From initiation of treatment to the first 48 weeks of treatment
Locations:
city: San Pa Tong
country: Thailand
facility: Sanpatong Hospital
state: Chiang Mai
city: Chiang Mai
country: Thailand
facility: Nakornping Hospital
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
city: Chon Buri
country: Thailand
facility: Chonburi Hospital
city: Samut Sakhon
country: Thailand
facility: Samutsakhon Hospital
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Gonzague Jourdain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: