Clinical trial NCT00756730: Lopinavir/r or Fosamprenavir/r Switch to Atazanavir/r or Darunavir/r
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: lopinavir
ritonavir
atazanavir
fosamprenavir
darunavir
anti-retroviral
AIDS
HIV
LARD
triglyceride
protease inhibitors
treatment Experienced
Lead sponsor: Community Research Initiative of New England
Sponsor class: OTHER
Collaborators: name: Tibotec Pharmaceutical Limited
First posted: 2008-09-22
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Patients That Experience 10% Decline in Triglycerides From Baseline to Week 24.
timeFrame: baseline, 24 weeks
measure: At Week 24 the Percentage of Subjects That Had Triglycerides Less Than 200 mg/dL
timeFrame: 24 weeks
measure: The Change in Fasting Triglyceride Level From Baseline to Week 24
timeFrame: Baseline to week 24
Secondary outcomes:
measure: Percent of Patients With HIV VL <200 Copies/mL at Week 4, 12 & 24
timeFrame: Week 4, 12 & 24
measure: Difference in CD4 From Baseline to Week 24
timeFrame: baseline to Week 24
measure: Total Cholesterol in the Two Study Groups at 24 Weeks
timeFrame: Week 24
measure: LDL Cholesterol at Week 24
timeFrame: week 24
measure: HDL Cholesterol at Week 24
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Los Angeles
country: United States
facility: AIDS Healthcare Foundation
state: California
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Boston
country: United States
facility: Community Research Initiative
state: Massachusetts
city: Springfield
country: United States
facility: Community Research Initiative - West
state: Massachusetts
city: Minneapolis
country: United States
facility: Abbott Northwestern Infectious Disease and Travel Clinic
state: Minnesota
city: Rochester
country: United States
facility: AIDS Community Health Center
state: New York
city: Philadelphia
country: United States
facility: Philadelphia Fight
state: Pennsylvania
city: Dallas
country: United States
facility: David M. Lee, M.D., P.A., a/b/a Uptown Physicians Group
state: Texas
city: Dallas
country: United States
facility: Nicholaos C. Bellos, MD, PA
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Community Research Initiative
name: Daniel J Skiest, MD
role: PRINCIPAL_INVESTIGATOR
References: