- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00814879
Pilot Study of a Raltegravir Based NRTI Sparing Regimen
A Pilot Randomized, Open-Label Study Comparing the Safety and Efficacy of a Raltegravir Based NRTI Sparing Regimen
Study Overview
Status
Intervention / Treatment
Detailed Description
The purpose of this pilot study is to compare the virological efficacy, as measured by the proportion of patients with plasma HIV-RNA below the limit of detection (<50 copies/mL), of two ARV regimens; patients are randomized to remain on regimens containing N(t)RTI(s) + PI/r or switch to Raltegravir + ATV but without N(t)RTI(s).
Study Arms:
- N(t)RTI(s) based backbone + PI/r
- Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID
Antiretroviral (ARV) treatment guidelines currently recommend ARV regimens containing a Nucleos(t)ide Reverse Transcriptase Inhibitors [N(t)RTI(s)] based backbone with a Non Nucleoside Reverse Transcriptase Inhibitor (NNRTI) or ritonavir boosted Protease Inhibitor (PI/r).(1) However, significant toxicity has been associated with N(t)RTI(s) and PI/r containing regimens. N(t)RTI(s) can cause lipoatrophy, lipid elevations, renal toxicity, neuropathy and lactic acidosis.(1) These toxicities have required clinicians and HIV-infected individuals to use alternative ARV regimens that do not use N(t)RTI(s). PIs are known to cause gastrointestinal side effects, dyslipidemia, and fat maldistribution (lipodystrophy).(1) The DHHS HIV treatment guidelines recommend that PIs should be given with a low dose of ritonavir (RTV). RTV is a PI that has an inhibitory effect on cytochrome P-450 3A4 isoenzyme which metabolizes most PIs. The addition of RTV serves as a pharmacokinetic "booster" by increasing PI drug concentrations.(1) However, RTV is known to increase PI side effects, elevate lipid levels and has significant drug-drug interactions with many medications given to HIV+ individuals.(1) These RTV drug interactions can complicate the medical care of an HIV-infected individual.
Raltegravir (RAL) is a recently FDA approved antiretroviral agent that inhibits HIV replication by blocking the integration of HIV proviral DNA into the host cell chromosomal DNA. RAL does not exhibit cross resistance to other ARV classes and thus has been initially used in HIV-infected individuals that are infected with drug resistant HIV strains. Recently published data on the use of RAL(2,3)in HIV-infected subjects with known ARV drug resistance or those without ARV drug resistance4 demonstrates that RAL is a potent agent, suppressing HIV viral loads in the majority of subjects and having excellent CD4 cell responses.(2-4) RAL is metabolized through glucuronidation by the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) enzyme pathway.(5)ATV is a known inhibitor of this enzyme pathway. ATV will increase RAL levels,(5) however, the current DHHS HIV treatment guidelines do not recommend a change in the dose of RAL if given with ATV as persons receiving ATV and RAL have demonstrated good tolerability of the combination and low side effect profiles.(1-3,5)
The availability of RAL provides an opportunity to examine alternative ARV strategies that may be equally efficacious and less toxic than those currently recommended in HIV treatment guidelines. Such combinations might include RAL+ATV regimen without a concomitant N(t)RTI(s) based backbone and/or the inclusion of RTV. However, there is little data available to date regarding such a combination. HIV care providers have already begun to use the combination of RAL+ unboosted ATV as the patients they care for are intolerant of RTV or have had major side effects/toxicity with N(t)NRTIs. More investigation is required to determine if RAL+ATV is an efficacious and safe alternative to RTV boosted PI based ARV strategies. Before a RAL based strategy that does not include N(t)RTIs or RTV can be compared to other ARV class strategies for long-term efficacy outcomes, preliminary data on a RAL+ATV based regimen is needed. This pilot study will provide data on the safety and efficacy of the combination of RAL 400mg BID + ATV 300 mg BID in ARV-experienced subjects that have a suppressed HIV viral load on a RTV boosted PI based regimen who are then switched to a regimen of RAL 400mg BID +ATV 300mg BID.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Connecticut
-
New Haven, Connecticut, United States, 06504
- Yale University School of Medicine
-
New Haven, Connecticut, United States, 06511
- Saint Raphael Healthcare System
-
Waterbury, Connecticut, United States, 06721
- Waterbury Hospital
-
West Haven, Connecticut, United States, 06516
- VA CT Healthcare Systems
-
-
Florida
-
Sarasota, Florida, United States, 34237
- Comprehensive Care Center, Inc (dba Community AIDS Network)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HIV-1 positive
- On stable ARV-therapy for a minimum of 4 months with a HIV viral load of < 50 copies
- Currently on a N(t)RTI(s) based backbone + PI/r
- No prior history of PI drug resistance (by historical genotype or phenotype)
- Aged > 18 years of age
- Written informed consent
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.
Exclusion Criteria:
- Prior exposure to Raltegravir or Elvitegravir
- A detectable HIV viral load >50 copies within the last 4 months
- An ARV change within the last 4 months
- History of PI drug resistance
- Prior virologic failure on an ATV containing regimen
- Prior history of intolerance to ATV
- Pregnant or nursing mothers
- Pre-existing grade 3 or above laboratory toxicity except for lipids:
- Absolute neutrophil count (ANC) < 750 cells/mL.
- Hemoglobin < 8.0 g/dL.
- Platelet count < 50 000 cells/mL.
- AST, ALT and alkaline phosphatase > 5 x ULN.
- Serum bilirubin > 5 x ULN.
- calculated creatinine clearance of <50mL/min/1.73m2
- Patients with chronic active hepatitis B infection defined by positive serum Hbs antigen
- Use of any prohibited medications and/or the use of proton pump inhibitors in ATV plus RAL containing regimens)
- Patients with current alcohol or illicit substance use that in judgment of investigator makes study adherence unlikely
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: a.
N(t)RTI(s) based backbone & PI/r
|
N(t)RTI(s) based backbone plus ritonavir boosted PI
|
Experimental: b.
Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID
|
400 mg BID
Other Names:
300 mg BID
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Reaching Virologic Failure at Week 48.
Time Frame: 48 Weeks
|
Virologic failure was defined by protocol as a plasma HIV RNA >50 c/mL on 2 consecutive occasions >7 days apart or > 10 000 c/mL on one occasion (in the absence of an intercurrent infection or recent immunization).
|
48 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With < 400 Copies HIV RNA/mL at Week 48
Time Frame: 48 weeks
|
48 weeks
|
|
CD4+ Cell Count
Time Frame: Weeks 24
|
Weeks 24
|
|
CD4+ Cell Count
Time Frame: Week 48
|
Week 48
|
|
Cholesterol
Time Frame: baseline, week 24, week 48
|
Total cholersterol (mg/dL)
|
baseline, week 24, week 48
|
Mean Change in Total Bilirubin (mg/dL) From Baseline
Time Frame: baseline and 48 weeks
|
mean change in total bilirubin from baseline
|
baseline and 48 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael J Kozal, MD, Yale University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Immunologic Deficiency Syndromes
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- HIV Integrase Inhibitors
- Integrase Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Raltegravir Potassium
- Atazanavir Sulfate
Other Study ID Numbers
- 0811004448
- Yale-No Nukes
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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