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

HIV Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01225705
• Other study ID #: UKB-2009-MED-I-JKR-01
• Secondary ID: 2009-015904-24
• Status: Withdrawn
• Phase: Phase 4
• First received: October 20, 2010
• Last updated: June 2, 2015
• Start date: October 2010
• Est. completion date: August 2012

Study information

• Verified date: October 2010
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C
• HIV

Intervention

Drug:
• raltegravir
Patients will be randomized 1:1 to either the experimental or the active control arm
• Atazanavir/ritonavir
Patients will be randomized 1:1 to either the experimental or the active control arm

Locations

Country	Name	City	State
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

Sponsors (8)

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

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Yes
Secondary	Secondary objectives	Other parameters of safety and efficacy will be compared between both arms		Yes