Safety Study of Raltegravir in HIV/HCV Co-infected Patients
Primary Purpose
HIV, Hepatitis C
Status
Withdrawn
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
raltegravir
Atazanavir/ritonavir
Sponsored by

About this trial
This is an interventional treatment trial for HIV
Eligibility 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
Sites / Locations
- Auguste Viktoria Hospital (AVK)
- Praxiszentrum Kaiserdamm
- Private Practice Dupke, Carganico, Baumgarten
- Department of Internal Medicine I, Bonn University
- University of Essen
- Infektiologikum Frankfurt
- University of Frankfurt
- Infektionsmedizinisches Centrum Hamburg (ICH)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Raltegravir
Atazanavir/ritonavir
Arm Description
45 patients will receive open label raltegravir, in addition to the common backbone tenofovir and emtricitabine
45 patients will receive open label atazanavir/ritonavir
Outcomes
Primary Outcome Measures
Primary objective
there is no difference in the rate of grade 1/2, or 3/4 ALT elevations
there is a higher incidence of grade 1 - 4 hyperbilirubinemias in the ATV/r arm
Secondary Outcome Measures
Secondary objectives
Other parameters of safety and efficacy will be compared between both arms
Full Information
NCT ID
NCT01225705
First Posted
October 20, 2010
Last Updated
June 2, 2015
Sponsor
University Hospital, Bonn
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
1. Study Identification
Unique Protocol Identification Number
NCT01225705
Brief Title
Safety Study of Raltegravir in HIV/HCV Co-infected Patients
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 Type
Interventional
2. Study Status
Record Verification Date
October 2010
Overall Recruitment Status
Withdrawn
Why Stopped
no pts recruited
Study Start Date
October 2010 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
University Hospital, Bonn
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
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Raltegravir
Arm Type
Experimental
Arm Description
45 patients will receive open label raltegravir, in addition to the common backbone tenofovir and emtricitabine
Arm Title
Atazanavir/ritonavir
Arm Type
Active Comparator
Arm Description
45 patients will receive open label atazanavir/ritonavir
Intervention Type
Drug
Intervention Name(s)
raltegravir
Intervention Description
Patients will be randomized 1:1 to either the experimental or the active control arm
Intervention Type
Drug
Intervention Name(s)
Atazanavir/ritonavir
Intervention Description
Patients will be randomized 1:1 to either the experimental or the active control arm
Primary Outcome Measure Information:
Title
Primary objective
Description
there is no difference in the rate of grade 1/2, or 3/4 ALT elevations
there is a higher incidence of grade 1 - 4 hyperbilirubinemias in the ATV/r arm
Secondary Outcome Measure Information:
Title
Secondary objectives
Description
Other parameters of safety and efficacy will be compared between both arms
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Auguste Viktoria Hospital (AVK)
City
Berlin
Country
Germany
Facility Name
Praxiszentrum Kaiserdamm
City
Berlin
Country
Germany
Facility Name
Private Practice Dupke, Carganico, Baumgarten
City
Berlin
Country
Germany
Facility Name
Department of Internal Medicine I, Bonn University
City
Bonn
Country
Germany
Facility Name
University of Essen
City
Essen
Country
Germany
Facility Name
Infektiologikum Frankfurt
City
Frankfurt / Main
Country
Germany
Facility Name
University of Frankfurt
City
Frankfurt / Main
Country
Germany
Facility Name
Infektionsmedizinisches Centrum Hamburg (ICH)
City
Hamburg
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Safety Study of Raltegravir in HIV/HCV Co-infected Patients
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