Efficacy and Tolerance of the Switch From Enfuvirtine to Raltegravir in Antiretroviral Therapy Regimen in HIV Patients With Undetectable Viral Load (EASIER)
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| ClinicalTrials.gov Identifier: NCT00454337 |
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Recruitment Status
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Completed
First Posted
: March 30, 2007
Last Update Posted
: November 7, 2012
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infections | Drug: FTC/TDF + EFV or LPV/R +T20 Drug: FTC/TDF + EFV or LPV/R | Phase 3 |
In patients who have failed under the three main classes of antiretroviral agents (NRTI, NNRTI and PI) and in whom the control of viral replication in the plasma has ultimately been achieved with enfuvirtide, the aim is to sustain this virological success for as long as possible to thus enable satisfactory immune reconstitution, avoid further accumulation of viral mutations conferring resistance to the drugs and protect the patient from the risk of opportunistic disease and death.
Indeed, enfuvirtide is the lead compound in the new class of antiretroviral drugs which inhibit the fusion of HIV-1 virus with its target cell. Its in vivo efficacy was demonstrated during the pivotal studies TORO 1 and 2. Despite its efficacy, maintaining long-term treatment with enfuvirtide is nonetheless difficult for patients because of the constraints related to twice-daily subcutaneous parenteral injections. Furthermore, these subcutaneous injections are associated with inflammatory reactions at the injection site in 98 per cent of patients, without any reduction in frequency or severity over time. It is thus critical for patients who are well controlled by enfuvirtide to be able to simplify their treatment by replacing enfuvirtide with another active compound taken by mouth, which would enable maintenance of the virological response and acceptable safety in patients who have usually failed under the three main classes of antiretroviral drugs. A new antiviral compound, viral integrase inhibitor called raltegravir, could be proposed instead of enfuvirtide.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 170 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Randomized Non-inferiority Study Comparing a Strategy Maintaining Current Enfuvirtide-based Antiretroviral Therapy to a Strategy Replacing Enfuvirtide by an Integrase Inhibitor (Raltegravir) in HIV-1 Infected Subjects With Plasma Hiv-1 RNA Levels Below 400 Copies Per ml.ANRS 138 EASIER |
| Study Start Date : | May 2007 |
| Actual Primary Completion Date : | September 2008 |
| Actual Study Completion Date : | September 2008 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Intensification arm
emtricitabine/TDF + efavirenz or lopinavir/ritonavir + enfuvirtide
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Drug: FTC/TDF + EFV or LPV/R +T20
emtricitabine 200mg/TDF 300mg (1 pill per day) + efavirenz 600mg (1 pill per day) or lopinavir/ritonavir (3 pills twice a day) + enfuvirtide 90mg twice a day
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Active Comparator: Standard arm
emtricitabine/TDF + efavirenz or lopinavir/ritonavir
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Drug: FTC/TDF + EFV or LPV/R
emtricitabine 200mg/TDF 300mg (1 pill per day) + efavirenz 600mg (1 pill per day) or lopinavir/ritonavir (3 pills twice a day)
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- comparison of the proportions of virologic failure, defined as two consecutive pVL above 400 cp per ml, through 24 weeks in enfuvirtide-maintained arm versus raltegravir arm [ Time Frame: W24 ]
- comparison of time to onset of virologic failure [ Time Frame: W24 and W48 ]
- proportions of pts with pVL under 50 and 400 cp per ml respectively at week 24 and week 48 ; [ Time Frame: W24 & W48 ]
- plasma viral mutations in the event of virologic failure, compared to HIV-DNA archived mutations at baseline; [ Time Frame: virologic failure ]
- change in CD4 levels [ Time Frame: between W0 and W48 ]
- incidence of HIV-related events [ Time Frame: between W0 and W48 ]
- drug plasma and male genital tract pharmacokinetics; [ Time Frame: W24 & W48 ]
- incidence and type of adverse events, including adverse reactions [ Time Frame: between W0 & W48 ]
- proportions of discontinuing allocated treatment strategy [ Time Frame: between W0 & W48 ]
- quality of life and adherence [ Time Frame: W4, W12, W24 and W48 ]
- morphological and metabolic disorders outcome [ Time Frame: between W0 & W48 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Chronic HIV-1 infection
- Treatment with a well-tolerated combination of antiretroviral drugs unchanged for at least 3 months, including enfuvirtide
- Absence of any uncontrolled opportunistic disease
- No restrictions on CD4 lymphocyte levels
- Plasma HIV-1 RNA below 400 copies per ml for at least 3 months (at least two consecutive tests below 400 copies per ml prior to inclusion in the study, not including that on W -4)
- For women of childbearing age, use of mechanical contraception during any sexual intercourse and negative pregnancy test (plasma ß HCG) at W -4
Exclusion Criteria:
- HIV-2 infection
- Plasma HIV-1 RNA levels above 400 copies/ml on one occasion during the 3 months prior to screening (or the pre-inclusion visit at W -4)
- Poor compliance with antiretroviral therapy current at W -4
- Current treatment with an investigational drug (except cohort ATU)
- Patient previously treated with an integrase inhibitor in the context of a clinical study
- Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception
- Multiple drug therapy ongoing or necessary in the foreseeable future for Kaposi's disease or lymphoma
- Treatment with interferon ongoing or necessary in the foreseeable future for chronic hepatitis B or C
- Acute hepatitis whatever the case, or decompensated cirrhosis
- Current treatment with interferon, interleukin or anti-HIV vaccine
- Any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol
- Significant biological abnormalities (hemoglobin below 8g per dl, polynuclear neutrophils below 750 per mm3, platelets below 50,000 per mm3, serum creatinine above 3 times the level deemed normal by the laboratory (N), ASAT or ALAT above 5N, serum lipase above 2N) and total bilirubin above 2N (except if the patient is receiving atazanavir or indinavir)
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Concomitant treatments including one or more compounds interacting with UGT1A1
- anti-infective agents: rifampicin/rifampin
- psychotropic/anti-epileptic drugs: phenytoin, phenobarbital.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00454337
| France | |
| Service des maladies infectieuses et tropicales Hopital Saint Louis | |
| Paris, France, 75010 | |
| Principal Investigator: | Nathalie De Castro, MD | AP-HP Hopital Saint Louis Paris | |
| Principal Investigator: | Jean M Molina, MD | AP-HP Hopital saint Louis Paris | |
| Study Chair: | Jean P Aboulker, MD | INSERM SC10 Villejuif France |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | French National Agency for Research on AIDS and Viral Hepatitis |
| ClinicalTrials.gov Identifier: | NCT00454337 History of Changes |
| Other Study ID Numbers: |
2007-000162-20 ANRS 138 EASIER |
| First Posted: | March 30, 2007 Key Record Dates |
| Last Update Posted: | November 7, 2012 |
| Last Verified: | November 2012 |
Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis ):
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HIV-1 infection enfuvirtide raltegravir treatment experienced |
Additional relevant MeSH terms:
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HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Raltegravir Potassium Emtricitabine Enfuvirtide Efavirenz |
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 HIV Integrase Inhibitors Integrase Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP2C9 Inhibitors |