Clinical trial NCT01225705: 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
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: HIV
Hepatitis C
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
Collaborators: name: Dr. Axel Baumgarten, Berlin
name: Dr. Christoph Stephan, Frankfurt/M
name: Dr. Stefan Esser, Essen
name: Dr. Keikawus Arastéh, Berlin
name: Prof. Dr. Hans-Jürgen Stellbrink, Hamburg
name: Dr. Thomas Lutz, Frankfurt/M
name: Dr. Jörg Gölz , Berlin
First posted: 2010-10-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Primary objective
Secondary outcomes:
measure: Secondary objectives
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Auguste Viktoria Hospital (AVK)
city: Berlin
country: Germany
facility: Praxiszentrum Kaiserdamm
city: Berlin
country: Germany
facility: Private Practice Dupke, Carganico, Baumgarten
city: Bonn
country: Germany
facility: Department of Internal Medicine I, Bonn University
city: Essen
country: Germany
facility: University of Essen
city: Frankfurt / Main
country: Germany
facility: Infektiologikum Frankfurt
city: Frankfurt / Main
country: Germany
facility: University of Frankfurt
city: Hamburg
country: Germany
facility: Infektionsmedizinisches Centrum Hamburg (ICH)
Study officials:
References: