Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r (LARD)

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Daniel Skiest, MD, Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT00756730
First received: September 18, 2008
Last updated: October 23, 2012
Last verified: October 2012

September 18, 2008
October 23, 2012
September 2008
June 2011   (final data collection date for primary outcome measure)
  • Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24. [ Time Frame: baseline, 24 weeks ] [ Designated as safety issue: No ]
    A 10% decline in triglycerides (TGs) was determined to be clinically significant. The percentage of people that experienced a 10% decline was calculated by dividing the number who had a decline of 10% TGs by the total number of participants in the arm.
  • At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The Change in Fasting Triglyceride Level From Baseline to Week 24 [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
The change in fasting triglyceride level from baseline to week 24
Complete list of historical versions of study NCT00756730 on ClinicalTrials.gov Archive Site
  • Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24 [ Time Frame: Week 4, 12 & 24 ] [ Designated as safety issue: Yes ]
  • Difference in CD4 From Baseline to Week 24 [ Time Frame: baseline to Week 24 ] [ Designated as safety issue: No ]
  • Total Cholesterol in the Two Study Groups at 24 Weeks [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • LDL Cholesterol at Week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  • HDL Cholesterol at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The proportion of patients with fasting triglycerides <200mg/dL at week 24
  • Fasting lipid profiles (total, LDL, and HDL cholesterol and triglycerides) in the two study groups at weeks 4, 12, 24
  • Change in lipid profiles at week 4, compared to baseline
  • Proportion of patients in each arm with VL<50 copies/mL at weeks 12 and 24
  • Proportion of patients with HIV VL <200 copies/mL at week 24
  • Symptoms distress and patient quality of life self assessment at weeks 4, 12 and 24
  • Incidence of grade 2-4 adverse events possibly related to study drug
  • Proportion of subjects who discontinue study due to adverse events prior to week 24
  • Adherence as measured by the M-MASRI adherence scale at each study visit
  • CD4 cell count responses in each group at week 24
Not Provided
Not Provided
 
Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r
Randomized, Open-label Study of Switch From Lopinavir/Ritonavir (LPV/r) or Fosamprenavir/Ritonavir (FPV/r) to Either Once Daily Atazanavir/Ritonavir (ATV/r) or Once Daily Darunavir/Ritonavir (DRV/r) (Plus Background Nucleoside Reverse Transcriptase Inhibitors) in Patients Experiencing Triglyceride Elevations While Receiving LPV/r or FPV/r.

For participants with HIV taking either lopinavir or fosamprenavir who have elevated triglycerides, this trial will study the change in triglycerides after switching protease inhibitors.

This Phase IV trial will look at lipid and virologic responses after a switch to a more lipid-friendly antiretroviral regimen. Participants will be randomized to receive either boosted atazanavir or boosted darunavir given once daily, along with background NRTIs. This 24-week study will require 4 visits after randomization for evaluation, monitoring, and lab studies.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: ATV/r
    Switch to ATV/r at a dose of 300mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.
    Other Name: Atazanavir/r
  • Drug: DRV/r
    We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. Switch to DRV/r at a dose 800mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.
  • Switch to DRV/r (800mg/100mg) QD
    We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. For this arm the sbject switched to DRV/r at a dose 800mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study.
    Intervention: Drug: DRV/r
  • Switch to ATV/r (300mg/100mg QD)
    We designed a study to determine if switching virologically suppressed patients on a regimen containing LPV/r or FPV/r to either DRV/r or ATV/r would result in improved TGs while maintaining virological suppression. For this are the subject switched to ATV/r at a dose of 300mg/100mg QD for 24 weeks. Subjects will continue to maintain their background NRTI drugs throughout the screening period and during the entire study
    Intervention: Drug: ATV/r
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
49
June 2011
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Currently receiving Antiretroviral Therapy (ART) regimen including LPV/r or FPV/r and > or equal to 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Patient must be on a stable regimen containing LPV/r or FPV/r for at least 12 weeks prior to screening.
  • Documentation of an undetectable Human Immunodeficiency Virus (HIV) viral load (VL<400 copies/ml) using an FDA approved assay for a minimum of twelve weeks prior to screening AND undetectable HIV viral load using an FDA approved ultrasensitive assay at screening.
  • No evidence of HIV protease resistance as defined by the Stanford HIV database
  • Currently receiving first protease inhibitor unless switch to LPV/r or FPV/r was for non-virologic reasons
  • Fasting triglycerides > 200 mg/dL
  • No ongoing issues that in the opinion of the investigator would lead to decreased ability to comply with the study procedures
  • If currently receiving a proton pump inhibitor, the dose is < omeprazole 20 mg or the equivalent dose of another proton pump inhibitor
  • If patient is receiving another lipid lowering medication, it must be at a stable dose

Exclusion Criteria:

  • Currently receiving an ART regimen other than > or equal to two NRTIs and either LPV/r or FPV/r
  • Prior use of darunavir or atazanavir
  • CDC Class C Illness diagnosed within 30 days of screening
  • Patient is currently receiving the following Hydroxamethylglutaryl-coA (HMGCoA) reductase inhibitor medications (statins): pravastatin, lovastatin, simvastatin
  • Patient is currently receiving a bile acid sequestrant (cholestyramine, colestipol, and colesevelam)
  • Grade 3 or 4 Laboratory abnormalities as defined by a standardized grading scheme based on the DAIDS table with the following exceptions:

    1. Pre-existing diabetes mellitus with asymptomatic, nonfasting glucose grade 3 elevations
    2. Subjects with asymptomatic grade 3 fasting triglyceride or cholesterol elevations
  • Clinical or laboratory evidence of clinically significant liver impairment/dysfunction disease or cirrhosis
  • Note: Individuals co-infected with chronic hepatitis B or C viruses will be allowed to enter the trial if their condition is clinically stable and they will not require therapy during the course of the study. Individuals diagnosed with acute viral hepatitis at screening will not be allowed to enroll during acute phase
  • Active substance abuse or significant psychiatric illness that in the opinion of the investigator might interfere with study compliance
  • Use of any investigational agents 30 days prior to screening
  • Life expectancy < 6 months in the opinion of the investigator
  • Pregnancy or breast feeding
  • Female subject of childbearing potential (i.e., heterosexually active, and not surgically sterile or at least two years post-menopausal) not using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00756730
08-09
Not Provided
Daniel Skiest, MD, Community Research Initiative of New England
Daniel Skiest, MD
Tibotec Pharmaceutical Limited
Principal Investigator: Daniel J Skiest, MD Community Research Initiative
Community Research Initiative of New England
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP