Prospective Evaluation of Etravirine for HIV-infected Patients in Need of Lipid-lowering Drugs (ETRALL)

This study has been completed.
Sponsor:
Collaborator:
Janssen-Cilag A.G., Switzerland
Information provided by (Responsible Party):
Calmy Alexandra, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01543035
First received: February 27, 2012
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

Dyslipidaemia, characterized by raised triglyceride and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol levels, is common in HIV-infected individuals, and has been associated with HIV infection itself and antiretroviral therapy (ART). These abnormalities are well-established markers of cardiovascular (CVD) risk in the general population. Studies have suggested an increased risk of CVD associated with ART exposure over and above that conveyed by traditional cardiovascular risk factors. In HIV population to reduce lipid parameters, the most usual clinical strategy remains to add a statin treatment.

Recent studies suggested ART switch can represent an interesting alternative to statins to reduce lipid plasma levels.

The purpose of this study is to evaluate the frequency with which the replacement of LPV/r (lopinavir/ritonavir), ATZ/r (atazanavir/ritonavir), DRV/r (darunavir/ritonavir) or EFV (efavirenz) by ETR (Etravirin) in dyslipidemic patients with suppressed viremia would obviate the necessity to administer statins.

A prospective, phase III study in which the statin treatment of dyslipidemic HIV patients on antiretroviral drugs (ARVs) will be interrupted during 4 weeks is proposed.

At week 4, patients qualifying for a lipid lowering drug (calculated LDL-C≥ 3mmol/L) will replace EFV, LPV/r, DRV/r or ATZ/r by ETR. The proportion of patients not qualifying anymore for a statin treatment at 12 weeks (i.e. after 8 weeks of ETR treatment) will be determined. Additionally, the lipid level changes will be assessed at 12 weeks. Inflammatory markers will be measured at baseline, at drug switch and at the end of the study

Study drug will be provided by the drug manufacturer (Janssen-Cilag, AG). Compliance for study drug will be done at week-4 and week-12, Returned study medication will be counted and the amount notified on the Case Report Form (CRF).


Condition Intervention Phase
HIV Infection
Drug: stop statin and switch to an antiretroviral drug with less impact on lipid metabolism
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Prospective Multicentric Trial Evaluating Etravirine for HIV Infected Patients in Need of Lipid Lowering Drugs: the ETRALL Trial

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Proportion of patients not qualifying anymore for statin treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • fasting lipids changes [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: December 2011
Study Completion Date: August 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etravirine switch
Patients in need of lipid-lowering drug switched from boosted PI or EFV to Etravirine
Drug: stop statin and switch to an antiretroviral drug with less impact on lipid metabolism
Switch from a boosted PI or efavirenz based ART regimen to etravirine 400 mg/day once daily for patients in need of lipid lowering drugs (statin) after one month wash out of statin

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • On statin treatment for at least 3 months (fluvastatin, simvastatin, pravastatin, rosuvastatin, or atorvastatin) for primary prevention of cardiovascular disease
  • HIV Ribonucleic Acid (RNA) below 50 copies/mL, minimum duration 3 months
  • On a stable (> 3 months) ARV treatment including at least one of the following drugs: LPV/r, ATZ/r, DRV/r, or EFV
  • No previous virological escape or virological escape documented with a genotype at the time of failure only showing a K103M mutation.

Exclusion Criteria:

  • Probability of cardiovascular complications of > 20% according to the Swiss GSLA ("Groupe de travail Lipide et Athérosclérose"/Swiss Atherosclerosis Association) guidelines
  • Previous cardiovascular disease (including stroke)
  • Known diabetes
  • Known intolerance of ETR
  • Presence of a documented drug mutation (excluding the K103M)
  • Regimen including non-boosted ATZ
  • Known hyperlipidemia before ARV initiation
  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: NCT01543035

Locations
Switzerland
Universitätsspital Basel Klinik für Infektiologie & Spitalhygiene
Bale, Switzerland, 4031
Inselspital PKT2B / Poliklinik für Infektiologie
Berne, Switzerland, 3010
HUG /Division des Maladies infectieuses Unité VIH/SIDA
Geneva, Switzerland, 1211
Hôpital Neuchâtelois - La Chaux-de-Fonds Service des Maladies infectieuses
La Chaux-de-Fonds, Switzerland, 2300
CHUV / Service des maladies infectieuses Médecine 2
Lausanne, Switzerland, 1011
Kantonsspital / Infektiologie und Spitalhygiene Departement Innere Medizin
St Gallen, Switzerland, 9007
Universitätsspital Zürich Division of Infectious Diseases and Hospital Epidemiology Department of Internal Medicine
Zurich, Switzerland, 8091
Sponsors and Collaborators
Calmy Alexandra
Janssen-Cilag A.G., Switzerland
Investigators
Principal Investigator: Calmy Alexandra, Md, PhD Geneva University Hospital
  More Information

Publications:

Responsible Party: Calmy Alexandra, MD, PhD, HIV department Director, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01543035     History of Changes
Other Study ID Numbers: ETRALL DR3215
Study First Received: February 27, 2012
Last Updated: December 11, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
HIV infection
lipid lowering drugs
etravirine
patient
statin treatment
EFV or boosted PI antiretroviral treatment

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Hypolipidemic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014