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

This study has been withdrawn prior to enrollment.
(no pts recruited)
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT01225705
First received: October 20, 2010
Last updated: June 2, 2015
Last verified: October 2010
  Purpose

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 Intervention Phase
HIV
Hepatitis C
Drug: raltegravir
Drug: Atazanavir/ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • Primary objective [ Designated as safety issue: Yes ]
    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:
  • Secondary objectives [ Designated as safety issue: Yes ]
    Other parameters of safety and efficacy will be compared between both arms


Enrollment: 0
Study Start Date: October 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225705

Locations
Germany
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
  More Information

No publications provided

Responsible Party: Rheinische Friedrich-Wilhelms-Universität Bonn, Germany, Bonn University
ClinicalTrials.gov Identifier: NCT01225705     History of Changes
Other Study ID Numbers: UKB-2009-MED-I-JKR-01, 2009-015904-24
Study First Received: October 20, 2010
Last Updated: June 2, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Atazanavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2015