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

Sponsor

Calmy Alexandra (Other)

Overall Status

Completed

CT.gov ID

NCT01543035

Collaborator

Janssen-Cilag A.G., Switzerland (Industry)

Enrollment

Locations

Arm

Duration (Months)

4.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Proportion of patients not qualifying anymore for statin treatment [12 weeks]

Secondary Outcome Measures

fasting lipids changes [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Universitätsspital Basel Klinik für Infektiologie & Spitalhygiene	Bale	Switzerland	4031
2	Inselspital PKT2B / Poliklinik für Infektiologie	Berne	Switzerland	3010
3	HUG /Division des Maladies infectieuses Unité VIH/SIDA	Geneva	Switzerland	1211
4	Hôpital Neuchâtelois - La Chaux-de-Fonds Service des Maladies infectieuses	La Chaux-de-Fonds	Switzerland	2300
5	CHUV / Service des maladies infectieuses Médecine 2	Lausanne	Switzerland	1011
6	Kantonsspital / Infektiologie und Spitalhygiene Departement Innere Medizin	St Gallen	Switzerland	9007
7	Universitätsspital Zürich Division of Infectious Diseases and Hospital Epidemiology Department of Internal Medicine	Zurich	Switzerland	8091