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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01225705
Recruitment Status : Withdrawn (no pts recruited)
First Posted : October 21, 2010
Last Update Posted : June 3, 2015
Dr. Axel Baumgarten, Berlin
Dr. Christoph Stephan, Frankfurt/M
Dr. Stefan Esser, Essen
Dr. Keikawus Arastéh, Berlin
Prof. Dr. Hans-Jürgen Stellbrink, Hamburg
Dr. Thomas Lutz, Frankfurt/M
Dr. Jörg Gölz , Berlin
Information provided by:
University Hospital, Bonn

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.

Condition or disease Intervention/treatment Phase
HIV Hepatitis C Drug: raltegravir Drug: Atazanavir/ritonavir Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open, Prospective Study to Compare the Safety and Efficacy of Raltegravir vs. Atazanavir / Ritonavir, Both in Combination With Tenofovir DF and Emtricitabine, in the Treatment of HIV-infection in ART Naive Subjects With HCV Co-infection.
Study Start Date : October 2010
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Raltegravir
45 patients will receive open label raltegravir, in addition to the common backbone tenofovir and emtricitabine
Drug: raltegravir
Patients will be randomized 1:1 to either the experimental or the active control arm
Active Comparator: Atazanavir/ritonavir
45 patients will receive open label atazanavir/ritonavir
Drug: Atazanavir/ritonavir
Patients will be randomized 1:1 to either the experimental or the active control arm

Primary Outcome Measures :
  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 Outcome Measures :
  1. Secondary objectives
    Other parameters of safety and efficacy will be compared between both arms

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01225705

Auguste Viktoria Hospital (AVK)
Berlin, Germany
Praxiszentrum Kaiserdamm
Berlin, Germany
Private Practice Dupke, Carganico, Baumgarten
Berlin, Germany
Department of Internal Medicine I, Bonn University
Bonn, Germany
University of Essen
Essen, Germany
Infektiologikum Frankfurt
Frankfurt / Main, Germany
University of Frankfurt
Frankfurt / Main, Germany
Infektionsmedizinisches Centrum Hamburg (ICH)
Hamburg, Germany
Sponsors and Collaborators
University Hospital, Bonn
Dr. Axel Baumgarten, Berlin
Dr. Christoph Stephan, Frankfurt/M
Dr. Stefan Esser, Essen
Dr. Keikawus Arastéh, Berlin
Prof. Dr. Hans-Jürgen Stellbrink, Hamburg
Dr. Thomas Lutz, Frankfurt/M
Dr. Jörg Gölz , Berlin

Responsible Party: Rheinische Friedrich-Wilhelms-Universität Bonn, Germany, Bonn University Identifier: NCT01225705     History of Changes
Other Study ID Numbers: UKB-2009-MED-I-JKR-01
2009-015904-24 ( EudraCT Number )
First Posted: October 21, 2010    Key Record Dates
Last Update Posted: June 3, 2015
Last Verified: October 2010

Additional relevant MeSH terms:
Hepatitis C
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Liver Diseases
Digestive System Diseases
Atazanavir Sulfate
Raltegravir Potassium
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors