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This study has been withdrawn prior to enrollment.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

History of Changes

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 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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Atazanavir Atazanavir sulfate Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:

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:

Secondary objectives
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 (Adult, Senior)
Sexes Eligible for Study:	All
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


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 ( EudraCT Number )
Study First Received:	October 20, 2010
Last Updated:	June 2, 2015

Additional relevant MeSH terms:


Hepatitis C Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Hepatitis Liver Diseases Digestive System Diseases Ritonavir Atazanavir Sulfate Emtricitabine 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 Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors HIV Integrase Inhibitors Integrase Inhibitors

ClinicalTrials.gov processed this record on June 23, 2017

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