Raltegravir Switch Study to Reduce Liver Fibrosis Progression in HIV-Hepatitis C Co-infection

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2016-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

HIV infection exerts a negative impact on the course of HCV infection. Co-infected individuals progress more rapidly to liver fibrosis, cirrhosis and ESLD compared to those infected with HCV alone. Some of the this accelerated fibrosis may be related to longterm chronic toxicity from protease inhibitor based ART.

Hypothesis: Switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI).

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Raltegravir-based Antiretroviral Versus Maintaining Any Other Antiretroviral Therapy in HIV Mono-infected Patients

NCT02210715

HIV Fatty Liver Nonalcoholic Steatohepatitis

COMPLETED PHASE4

Efficacy and Tolerance of the Switch From Enfuvirtine to Raltegravir in Antiretroviral Therapy Regimen in HIV Patients With Undetectable Viral Load

NCT00454337

HIV Infections

COMPLETED PHASE3

Raltegravir Added to Stable HAART in HIV-1 Infected Subjects With Viral Suppression and Low CD4 Recovery

NCT00562510

HIV Infections

TERMINATED PHASE3

Quality of Life of HIV-infected Participants Switched to Raltegravir Versus Other Antiretroviral Regimens (MK-0518-266)

NCT01814722

Human Immunodeficiency Virus

TERMINATED

Protease Inhibitor Vs. Raltegravir-based ART and Inflammation in HIV Infection

NCT02691065

HIV

COMPLETED PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Primary Objective-To assess if switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI) after 48 weeks of treatment.

Secondary Objectives:

(i) To assess the safety and tolerability of switching from a ritonavir boosted-PI ART regimen to a raltegravir-based regimen for 48 weeks.

(ii) To evaluate hepatic function (liver enzymes) at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.

(iii) To evaluate the effect of switching treatment on control of HIV infection (as measured by HIV viral load and CD4) at weeks 0, 4, 8, 12, 24, 36, 48, and 72 post switch.

(iv) To evaluate metabolic profiles (e.g, fasting lipid profiles, glucose and insulin) at weeks 0, 24, 48 and 72 post switch.

(v) To evaluate inflammatory markers associated with liver fibrosis at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.

Population: Patients will be selected from CTN222; a Canadian National multisite prospective cohort of HCV-HIV infected persons (N=978) or from other eligible patients followed at participating sites. All patients recruited into the cohort are adults aged over 16 years old with documented HIV infection (ELISA with western blot confirmation) and with chronic HCV infection or evidence of HCV exposure (e.g. HCV-seropositive by ELISA with RIBA II or EIA confirmation, or if serologically false negative, HCV RNA+).

Study Design: A Randomized Prospective Open label study

Sample Size:

N = 40 This is a Phase II study designed to evaluate the safety and feasibility of a switch to raltegravir in HIV-HCV co-infected patients. As neither the duration of time required to improve fibrosis nor the potential impact of such a switch currently is known, this trial will provide important pilot data with which to estimate the true effect size and calculate the sample size required to conduct a larger definitive study on this question. It is hypothesized that switching therapy will lead to significant reduction in fibrosis as measured by APRI and FibroScan®. In other studies, for example, of successful HCV treatment using FibroScan®, a 34% reduction in fibrosis score was observed in those obtaining a sustained virologic response at 48 weeks (e.g., from mean baseline score of 10.3 kPa to 6.6 kPa at 48 weeks; s.d.= 5 kPa 1). We propose a sample size of 20 patients in each group, which would provide approximately 80% power to detect at least a difference of 5 kPa in fibrosis score change between the two groups assuming a similar standard deviation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Hepatitis C Liver Fibrosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

ritonavir-boosted protease inhibitor

Group Type ACTIVE_COMPARATOR

Raltegravir

Intervention Type DRUG

Subjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks.

Ritonavir-boosted protease inhibitor

Intervention Type DRUG

Subjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks

Raltegravir

Group Type EXPERIMENTAL

Raltegravir

Intervention Type DRUG

Subjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks.

Ritonavir-boosted protease inhibitor

Intervention Type DRUG

Subjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Raltegravir

Subjects will maintain their nucleoside backbone and switch ritonavir-boosted protease inhibitor to Raltegravir 400 mg po BID for 48 weeks.

Intervention Type DRUG

Ritonavir-boosted protease inhibitor

Subjects will maintain their nucleoside backbone and remain on a ritonavir-boosted protease inhibitor at standard doses for for 48 weeks

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Isentress MK-0518 RGV Kaletra Lopinavir-ritonavir Atazanavir-ritonavir Reyataz-norvir Darunavir-ritonavir Presista-norvir

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 18 years or older
2. Chronic HIV-HCV co-infection (HCV RNA + for at least 6 months and could have had previous HCV treatment).
3. Receiving ritonavir boosted PI-based ART for at least 6 months.
4. APRI score ≥ 1.5 (equivalent to liver biopsy score of ≥ F2) AND/OR Fibroscan \> 6.9KPa
5. HIV viral suppression (\<50 copies/mL) for at least 6 months.
6. No prior evidence of resistance to raltegravir or co-administered nucleoside backbone.
7. No prior history of virologic failure.

Exclusion Criteria

1. Clinical evidence of decompensated liver disease (e.g., ascites, esophageal varices, or hepatic encephalopathy hepatoma or hepatocellular carcinoma).
2. Chronic Hepatitis B infection (defined as positive HBsAg or Hepatitis B viral load greater than 10,000 copies/mL).
3. AFP greater than or equal to 200 ng/mL at screening.
4. Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease.
5. Chronic renal insufficiency (eGFR \< 20 mL/min) at screening.
6. Pregnancy and planned pregnancy (WOCBP not using adequate contraception).
7. Women who are breastfeeding.
8. Active opportunistic infection (except oral thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, or cancer of the cervix or anus, unless known or suspected liver metastasis).
9. Patients intending to start HCV therapy within the treatment phase (within the year following the baseline visit).

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No