Study Comparing Efficacy and Safety of Darunavir Boosted With Ritonavir to HART With 2 NRTI and Darunavir Boosted With Ritonavir in HIV-1 Infected Patients ANRS136
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00421551 |
|
Recruitment Status
:
Completed
First Posted
: January 12, 2007
Last Update Posted
: July 18, 2013
|
Sponsor:
French National Agency for Research on AIDS and Viral Hepatitis
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
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 )
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
The purpose of this study is to evaluate whether a monotherapy of boosted darunavir is able to maintain the virological success until 48 weeks in comparison to a standard therapy 2 INTI + darunavir/r in HIV infected patients with full viral suppression.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infections | Drug: Darunavir Drug: ritonavir | Phase 3 |
The chronicity of the disease which will require treatment over decades, long-term adverse events associated with standard combined antiretroviral therapy, emphasize the need for simpler, alternative treatment strategies for HIV infection. The goal of antiretroviral therapy in 2006 is the durability of treatment with less toxicity and reduced exposure to drugs. Previous studies have shown that single boosted PI maintenance therapy such as lopinavir (LPV/r), were effective in maintaining virological efficacy. Furthermore, in case of virological failure, limited resistance has been described. darunavir/r, a new PI, has been shown to be highly potent, exhibits a high genetic barrier to resistance and appears to be well tolerated. This study aimed to evaluate whether darunavir/r can represent a potential strategy therapeutic as single therapy in patients who have full virologic suppression At entry, subjects with HIV RNA below 50 cp/ml switch from their current therapy which can be 2 NRTI and IP, 2 NRTI and NNRTI, 3 NRTI to darunavir/r with their 2 NRTIs for 8 weeks (Phase I). If patients remain below 50 cp/ml and has no intolerance to darunavir at week -4, they are included in the phase II and will be randomized either to receive darunavir/r alone or to continue 2 NRTI and darunavir/r for until W48 (Phase II). Patients will be monitored at W4, W8 and then every 8 weeks until W48 for the primary endpoint. To evaluate the durability and safety of this strategy, patients will be followed up to W96
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 225 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized Multicenter Study With Non-inferiority Hypothesis, Comparing the Availability to Maintain a Complete Viral Suppression by a Monotherapy of Darunavir/r to a NRTI Containing Regimen Including Darunavir/r, in HIV-1 Infected Patients With Previous Prolonged Complete Viral Suppression. ANRS 136 MONOI |
| Study Start Date : | March 2007 |
| Actual Primary Completion Date : | June 2010 |
| Actual Study Completion Date : | February 2011 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
HIV/AIDS
U.S. FDA Resources
| Arm | Intervention/treatment |
|---|---|
| Experimental: 1 |
Drug: Darunavir
during the 48 first weeks of the trial, (2x300mg) twice a day between W48 and W96, (2x400mg) once a day
Other Name: Prezista
Drug: ritonavir
during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day
Other Name: Norvir
|
| Active Comparator: 2 |
Drug: Darunavir
during the 48 first weeks of the trial, (2x300mg) twice a day between W48 and W96, (2x400mg) once a day
Other Name: Prezista
Drug: ritonavir
during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day
Other Name: Norvir
|
Primary Outcome Measures
:
- Proportion of patients with virological success, the virological failure is defined as 2 consecutive plasma viral load measurements greater or equal to 400 cp/ml within 2 weeks at W48 [ Time Frame: W48 ]
Secondary Outcome Measures
:
- Proportion of patients with virological success between W48 and W96, [ Time Frame: W96 ]
- Proportion of patients with HIV-1 RNA below 50 copies/mL, between 50 to 400 copies/mL and > 400 copies/ml from D0 to W96, [ Time Frame: W96 ]
- Time to virologic failure, [ Time Frame: between W0 and W96 ]
- PI genotypic resistance mutations occurring during the follow-up [ Time Frame: between W0 and W96 ]
- Change in proviral DNA at D0, W48 and W96, [ Time Frame: W0, W48 and W96 ]
- Change in CD4 count from D0 to W96. [ Time Frame: D0, W96 ]
- Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry [ Time Frame: D0 ]
- Quantification of HIV RNA in the genital compartment between D0 and W48 (sub-study with 40 patients enrolled, 20 patients in each arm of strategy). [ Time Frame: D0 and W48 ]
- Incidence of clinical endpoints [ Time Frame: W96 ]
- Modification of treatment strategies and withdrawal of study treatment. [ Time Frame: between D0 and W96 ]
- Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms). [ Time Frame: between D0 and W96 ]
- Change in lipidic and glucidic profile and distribution of fat tissue by DEXA-scan (sub-study in 160 patients enrolled). [ Time Frame: W0, W48 and W96 ]
- Self-reported adherence and symptom self-evaluation. [ Time Frame: W0, W4, W24, W48, W96 ]
- The proportion of patients with HIV RNA below 50 copies/mL in darunavir/r monotherapy arm after resuming 2 previous NRTIs in case of virological failure. [ Time Frame: between W0 and W96 ]
- Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …). [ Time Frame: between W0 and W96 ]
- evaluation of the mineral bone density by DEXA-scan (sub-study in 160 patients enrolled). [ Time Frame: W96 ]
Information from the National Library of Medicine
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Confirmed HIV-1 infection.
- Documented level of HIV-1 RNA at initiation of antiretroviral treatments
- Prior antiretroviral regimen, including at least 2 NRTIs combined to 1 PI or NNRTI or a third NRTI for at least 18 months prior to study entry.
- CD4 count of 200 cells per mm3 or greater.
- Viral load below 400 copies per ml within 18 months prior to entry and below 50 copies per mL at entry.
- Willing to use acceptable methods of contraception
Exclusion Criteria:
- Previous virological failure under prior PI-based regimen.
- Prior therapy in the darunavir.
- HIV-2 infected patients.
- Absence of documented level of HIV-1 RNA at initiation of antiretroviral treatments
- Hepatitis B or C infection within 90 days prior to study entry.
- Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry.
- Serious acute illness requiring systemic treatment or hospitalization in the 14 days prior to study entry.
- Treatment for an active AIDS defining opportunistic infection within 30 days prior to screening
- Drug or alcohol use or any dependence that would interfere with compliance.
- Pregnancy or breastfeeding
Information from the National Library of Medicine
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): NCT00421551
Locations
| France | |
| Service des maladies infectieuses et tropicales Hopital Pitie salpetriere | |
| Paris, France, 75013 | |
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Tibotec Pharmaceutical Limited
Investigators
| Principal Investigator: | Christine Katlama, MD | AP-HP hopital Pitié salpetriere Paris | |
| Study Chair: | Philippe Flandre | Inserm UMR S720 |
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: | NCT00421551 History of Changes |
| Other Study ID Numbers: |
2006-005962-38 ANRS 136 MONOI |
| First Posted: | January 12, 2007 Key Record Dates |
| Last Update Posted: | July 18, 2013 |
| Last Verified: | July 2013 |
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 ):
|
HIV Infections darunavir Ritonavir HIV Protease Inhibitors treatment experienced |
Additional relevant MeSH terms:
|
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 Darunavir |
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 |