Clinical trial NCT00543101: Efficacy Study of Substitution of Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors
Official title: A Randomized, Controlled Trial to Evaluate the Efficacy of Substituting Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors in Individuals With Virologic Suppression for at Least 12 Weeks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV/AIDS
darunavir
Protease inhibitors
Dual boosted
Treatment experienced
Lead sponsor: Community Research Initiative of New England
Sponsor class: OTHER
First posted: 2007-10-12
Enrollment: 24
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: This study will evaluate patients who have achieved virologic suppression (\< 400 copies/mL) on any dual protease inhibitor (PI) combination, to determine whether patients can substitute both PIs with the single boosted PI darunavir given 600/100 ritonavir (RTV) twice daily (BID) and maintain comparable virologic suppression (% \< 50 c/mL) for 24 weeks.

Detailed description: The purpose of this study is to determine if patients who have achieved virologic suppression (\< 400 copies/mL) on any dual PI combination, can substitute both PIs with the single boosted PI darunavir given 600/100 rtv bid and maintain comparable virologic suppression (% \< 50 c/mL) for 24 weeks. Randomized, non-blinded, multicenter, 48 week, controlled trial to assess the non-inferiority of substituting DRV/r for a dual boosted PI combination in patients with stable virologic suppression on a regimen containing a dual boosted PI combination plus at least one additional FDA-licensed antiretroviral agent from another class. Participants will be randomized (1:1) to one of the included treatment arms.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* Treatment with a stable antiretroviral regimen containing two protease inhibitors, one additional FDA-licensed agent from another class (except NNRTIs) and a boosting dosage of ritonavir (100 BID or QD) for at least 12 weeks prior to screening
* No plans to make any changes in HIV treatment regimen (other than those required by study) in the next 48 weeks.
* HIV-1 RNA \< 400 copies/ml based on the most recent value done as part of routine care at least 12 weeks prior to screening; and \< 400 at screening
* Any CD4 count is allowed
* Written informed consent to participate

Exclusion Criteria:

* Current regimen includes an NNRTI
* CDC Class C Illness diagnosed within 30 days of screening
* Lab abnormalities as defined by a standardized grading scheme based on the DAIDS table
* Any grade 3 or 4 toxicity with the following exceptions:

  * Pre-existing diabetes with glucose elevations ≥ grade 3
  * triglyceride or total cholesterol elevations ≥ grade 3
* Clinical or laboratory evidence of clinically significant liver impairment/dysfunction, disease or cirrhosis Note: Individuals co-infected with chronic hepatitis B or C will be allowed to enter the trial if their condition is clinically stable. 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
* Prior use of darunavir or known allergy to any of the components of darunavir
* Breast feeding
* Female subject of childbearing potential 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.

Note: Hormonal based contraception may not be reliable when taking darunavir, therefore to be eligible for this study, women of childbearing potential who may have vaginal intercourse should either:

1. Use a double barrier method to prevent pregnancy (i.e., using a condom with either a diaphragm or cervical cap) Or
2. Use hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or
3. Use an intra uterine device (IUD) in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or
4. Be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile).

Primary outcomes:
measure: The Percentage of Participants With Successful Virologic Suppression
timeFrame: 24 weeks
Secondary outcomes:
measure: Economic Impact of a Substitution of Dual Boosted PIs With DRV/r
timeFrame: 48 weeks
measure: Lipid Fraction Results, Mean of the Change From Baseline to Week 24.
timeFrame: baseline and 24 weeks
measure: Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now)
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 of New England
state: Massachusetts
city: Albany
country: United States
facility: Albany Medical Center
state: New York
Study officials:
affiliation: CRI
name: Calvin J Cohen, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: