Safety Study of Raltegravir in HIV/HCV Co-infected Patients

NCT01225705 | Withdrawn Phase 4

• 2 other identifiers: UKB-2009-MED-I-JKR-012009-015904-24
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 8

Brief Summary

Current European AIDS Clinical Society (EACS) guidelines for the treatment of HIV infection recommend a combination antiretroviral regimen composed of two nucleoside reverse transcriptase inhibitors plus a ritonavir boosted protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. The non-nucleoside reverse transcriptase inhibitors licensed for naïve patients - nevirapine and efavirenz - have both been asociated with increased rates of hepatotoxicity (nevirapine) and CNS toxicity (efavirenz) in HIV/HCV co-infected patients. Although PI-based therapy has dramatically reduced morbidity and mortality, it has been limited by complex dosing regimens and toxicities, leading to adherence challenges. Varying degree of liver insufficiency may necessitate pharmacokinetic monitoring of the protease inhibitor and may necessitate dose adjustments. In HIV/HCV co-infected patients HAART based on another class of antiretrovirals than NNRTI or PI may thus offer advantages with regard to adverse events and thus long-term efficacy. The overall intention of this trial is to examine in a non-inferiority design the safety and efficacy of a raltegravir based HAART with a standard-of-care HAART in HIV-/HCV co-infected patients. The standard of care used in this study will be atazanavir/ritonavir. All patients will in addition receive a fixed combination of tenofovir and emtricitabine. The primary end-point is the rate of hepatotoxic events, defined by ALT elevations.

Conditions

HIV; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Primary objective

  1. there is no difference in the rate of grade 1/2, or 3/4 ALT elevations 2. there is a higher incidence of grade 1 - 4 hyperbilirubinemias in the ATV/r arm

Secondary Outcomes (1)

• Secondary objectives

Study Arms (2)

Raltegravir

EXPERIMENTAL

45 patients will receive open label raltegravir, in addition to the common backbone tenofovir and emtricitabine

Drug: raltegravir

Atazanavir/ritonavir

ACTIVE COMPARATOR

45 patients will receive open label atazanavir/ritonavir

Drug: Atazanavir/ritonavir

Interventions

raltegravir DRUG

Patients will be randomized 1:1 to either the experimental or the active control arm

Raltegravir

Atazanavir/ritonavir DRUG

Patients will be randomized 1:1 to either the experimental or the active control arm

Atazanavir/ritonavir

Eligibility Criteria

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

You may qualify if:

• HIV and Hepatitis C co-infected patients
• indication for HAART according to current German-Austrian guidelines
• HAART naive
• no primary NRTI / Integrase / PI associated resistance mutation according to the Stanford algorithm at screening; every patient MUST have a genotypic resistance assay prior baseline available (\< 6 months prior to baseline)
• women of childbearing age: negative pregnancy test
• ability to sign written informed consent

You may not qualify if:

• advanced liver cirrhosis Child-Pugh B or C or decompensated liver disease
• Pegylated interferon / ribavirin or other anti-HCV therapy; planned anti-HCV therapy for duration of the study (48 weeks).
• acute or chronic hepatitis B infection
• acute hepatitis A or other hepatotropic virus infections
• any other chronic liver disease such as alcohol abuse or hemosiderosis
• use or planned use (for the duration of the study, 48 weeks) of rifampicin, St. John´s wort and drugs that are metabolized via the cytochrome P450 system with a narrow therapeutic PK-range such as astemizole, terfenadine, cisapride, pimozide, chinidin, bepridil, triazolam, midazolam, ergotamine, dihydroergotamin, ergometrine, methyl-ergometrine. FOR OTHER COMEDICATIONS please consult with the SPC of Raltegravir (Isentress®), Atazanavir (Reyataz®), Ritonavir (Norvir®), your hospital pharmacist, www.hiv-drug-interactions.org or the principal investigator in case of uncertainty.
• new AIDS defining event, except for Kaposi sarcoma, \< 1 months prior to screening
• malignancy, except for Kaposi sarcoma, with current radio- or chemotherapy
• history of organ transplantation

Sponsors & Collaborators

• University Hospital, Bonn: lead
• Dr. Axel Baumgarten, Berlin: collaborator
• Dr. Christoph Stephan, Frankfurt/M: collaborator
• Dr. Stefan Esser, Essen: collaborator
• Dr. Keikawus Arastéh, Berlin: collaborator
• Prof. Dr. Hans-Jürgen Stellbrink, Hamburg: collaborator
• Dr. Thomas Lutz, Frankfurt/M: collaborator
• Dr. Jörg Gölz , Berlin: collaborator

Study Sites (8)

Auguste Viktoria Hospital (AVK)

Berlin, Germany

Location

Praxiszentrum Kaiserdamm

Berlin, Germany

Location

Private Practice Dupke, Carganico, Baumgarten

Berlin, Germany

Location

Department of Internal Medicine I, Bonn University

Bonn, Germany

Location

University of Essen

Essen, Germany

Location

Infektiologikum Frankfurt

Frankfurt am Main, Germany

Location

University of Frankfurt

Frankfurt am Main, Germany

Location

Infektionsmedizinisches Centrum Hamburg (ICH)

Hamburg, Germany

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Raltegravir Potassium; atazanavir, ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 20, 2010
• First Posted: October 21, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: June 3, 2015

Record last verified: 2010-10

Locations

DE (8)