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| Sponsors and Collaborators: |
Stanford University Bristol-Myers Squibb |
|---|---|
| Information provided by: | Stanford University |
| ClinicalTrials.gov Identifier: | NCT00160329 |
Purpose
The study is looking to compare the impact of lipid levels and HIV viral loads between three different drug regimens: Continuing current regimen (ritonavir boosted regimen), Switching to Atazanavir, or Switching to Atazanavir in combination to Ritonavir.
| Condition | Intervention | Phase |
|---|---|---|
|
Hyperlipidemia HIV Infections |
Drug: Atazanavir |
Phase III |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | The De-Esculate Trial: Atazanavir or Atazanavir/Ritonavir Substitution for Ritonavir Boosted PI Therapy in HIV-Infected Individuals Experiencing Ongoing HIV Viremia and Hyperlipidemia: A Randomized Controlled Pilot Study |
| Estimated Enrollment: | 60 |
Study Overview
This is a randomized controlled pilot study to compare the safety and efficacy of substitution of atazanavir (ATV) or ATV/RTV for ritonavir boosted PI in patients with ongoing viremia who are experiencing hyperlipidemia and/or requiring treatment with lipid lowering agents. In this study 60 subjects on a ritonavir boosted PI-containing antiretroviral regimen who are experiencing hyperlipidemia and ongoing HIV viremia will be randomized in a 1:1:1 ratio to either switch the ritonavir boosted PI component of the antiretroviral regimen to ATV or ATV/RTV, or continue the ritonavir boosted PI-based regimen.
No other changes in the antiretroviral regimen will be allowed for the first 12 weeks. Thereafter, the investigator may change background ARVs based on the results of the screening resistance test. No new class of antiretrovirals will be allowed to be added through 48 weeks. Subjects will be monitored closely over 48 weeks with careful assessment of CD4 profile, viral loads and lipid profiles as well as drug resistance and replication capacity. Stopping rules will be implemented based on CD4 and viral load profile to ensure subject safety. The objective of this study is to determine whether protease inhibitor regimens that have less of an adverse impact on lipid profiles can maintain a stable CD4 profile compared to standard ritonavir boosted PI regimens.
Background
Antiretroviral regimens that include ritonavir-boosted protease inhibitors are commonly recommended and prescribed, particularly in patients with some degree of drug resistance. Despite the potency of boosted regimens, many HIV-infected patients receiving these regimens have incomplete viral suppression and yet maintain clinical stability and CD4 counts above nadir levels: the so called 'CD4/HIV disconnect' state. It is likely that this state of CD4/HIV discordance is due in part to the maintenance of drug resistant HIV virus that is relatively unfit, that is its replication capacity and ability to infect and destroy CD4 cells is compromised. The selective pressure exerted by antiretroviral therapy appears to be important in maintaining these drug resistant but relatively unfit quasispecies. It has been shown that even patients with CD4 counts below 50 cells/cc and ongoing viremia maintain a clinical benefit from continued therapy.
Unfortunately, lipid abnormalities are commonly seen in patients receiving boosted PI regimens. For example, in a clinical trial in which lopinavir/ritonavir (LPV/r) was given to treatment naïve subjects, approximately 1/3 developed grade 2 or higher lipid abnormalities over 48 weeks. There is a growing concern that these lipid abnormalities will increase the risk of cardiovascular morbidity and mortality. In fact, recent data suggest an increased risk of cardiovascular morbidity and mortality related to HIV infection and/or antiretroviral therapy. There are increasing efforts directed at minimizing long-term toxicities of antiretroviral therapy while maintaining its clinical benefit. (Witness the high degree of interest in treatment interruptions as a strategy to limit toxicities associated with long-term antiretroviral therapy.)
Atazanavir (ATV), a recently approved PI, appears to have little to no impact on the lipid profile in subjects enrolled in clinical trials. Other advantages with atazanavir are its dosing schedule and overall tolerability. Furthermore, recent studies using ritonavir-boosted ATV also show favorable lipid effects compared to LPV/r. Ritonavir boosting provides higher drug levels and therefore may improve the potency of ATV, especially against PI-resistant virus.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:Stable primary care
All women of reproductive potential (who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) must have a negative serum or urine ²-HCG pregnancy test performed within 48 hours of entry.
Female study volunteers who are not of reproductive potential (who have reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) or whose male partner has undergone successful vasectomy with documented azoospermia or has documented azoospermia for any other reason, are eligible without requiring the use of contraception. Acceptable documentation of menopause, sterilization, and azoospermia are as follows:
Written or oral documentation communicated by clinician or clinician's staff of one of the following:
2. Subjects who use substances or with a mental health condition that would in the opinion of the treating clinician interfere with the ability of the subject to comply with study treatment and monitoring.
3. Subjects who have significant liver disease defined as AST (SGOT) and ALT (SGPT) > 5 x ULN.
4. Subjects who have a history of an acute opportunistic infection within 8 weeks prior to study screening. Chronic infections will not be excluded.
5. Subjects who have received a vaccination within 2 weeks prior to study screening.
6. Subjects who are receiving experimental ARV therapy.
7. Subjects who are receiving systemic chemotherapy.
8. Subjects who are receiving IL-2 or IFN-alpha.
9. Subjects who are receiving GM-CSF.
10. Subjects who have any grade 3-4 laboratory abnormality or clinical AE, other than lipid abnormalities.
11. Prior use of Atazanavir
12. Subjects who have a history of
Contacts and Locations| United States, California | |
| Stanford University School of Medicine | |
| Stanford, California, United States, 94305 | |
| Principal Investigator: | Andrew R Zolopa | Stanford University |
More Information
| Study ID Numbers: | De-Escalate Trial, IRB # 79603, Spo# 29750 |
| Study First Received: | September 8, 2005 |
| Last Updated: | March 14, 2008 |
| ClinicalTrials.gov Identifier: | NCT00160329 |
| Health Authority: | United States: Institutional Review Board |
|
Sexually Transmitted Diseases, Viral Hyperlipidemias Metabolic Diseases Acquired Immunodeficiency Syndrome Atazanavir Immunologic Deficiency Syndromes Virus Diseases Ritonavir |
HIV Infections Sexually Transmitted Diseases Viremia Metabolic disorder Retroviridae Infections Dyslipidemias Lipid Metabolism Disorders |
|
Anti-Infective Agents RNA Virus Infections HIV Protease Inhibitors Slow Virus Diseases Anti-HIV Agents Immune System Diseases Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |
Infection Antiviral Agents Pharmacologic Actions Protease Inhibitors Anti-Retroviral Agents Therapeutic Uses Lentivirus Infections |
