Efficacy Study of Substitution of Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors (DVD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cal Cohen, Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT00543101
First received: October 11, 2007
Last updated: February 9, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Darunavir (DRV/r)
Drug: continue on current dual boosted PI
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Community Research Initiative of New England:

Primary Outcome Measures:
  • The Percentage of Participants With Successful Virologic Suppression [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Amount of HIV RNA copies per ml blood collected from subjects as measured by the Ultra-sensitive HIV-1 PCR (Roche Cobas). Successful virologic suppression is defined as < 50 copies/ml blood. The result is the percentage of participants with successful virologic suppression.


Secondary Outcome Measures:
  • Economic Impact of a Substitution of Dual Boosted PIs With DRV/r [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    To assess the economic impact of DRV/r substitution for dual boosted PIs, we compared the average wholesale acquisition costs for the drugs in US Dollars ($) per month. The wholesale acquisition cost in US dollars ($) for each ART regimen was determined and the difference between the cost for the experimental and control groups was calculated and reported as US dollar savings per month.

  • Lipid Fraction Results, Mean of the Change From Baseline to Week 24. [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]
    We collected fasting total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides from all participants in both arms of the study. We calculated the differences between the values at week 24 and baseline for the participants in both arms. We reported the mean of the change from baseline to week 24.

  • Treatment Satisfaction (+3, Much More Satisfied Now to -3, Much Less Satisfied Now) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Participants in the experimental arm completed treatment satisfaction questionnaires at 24 weeks, and the control arm at 48 weeks (24 weeks after mid-study crossover to boosted darunavir). The questionnaires used numeric satisfaction scales (+3 much more satisfied now to -3 much less satisfied now). We reported the median and ranges for each question for each study arm.


Enrollment: 24
Study Start Date: October 2007
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Switch to DRV/r
Switch to DRV/r at a dose of 600/100 BID for 48 weeks
Drug: Darunavir (DRV/r)
Switch to DRV/r at a dose of 600/100 BID for 48 weeks
Active Comparator: Continue on Current Dual Boosted PI
Continue on current dual boosted PI until week 24. At week 24, participants will be allowed to cross over to the DRV/r arm provided that they have maintained virologic suppression (< 400 copies/ml) for the first 24-weeks of the study and are followed for an additional 24 weeks
Drug: continue on current dual boosted PI
Continue on current dual boosted PI until week 24. At week 24, participants will be allowed to cross over to the DRV/r arm provided that they have maintained virologic suppression (< 400 copies/ml) for the first 24-weeks of the study and be followed for an additional 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00543101

Locations
United States, Arizona
Spectrum Medical Group
Phoenix, Arizona, United States, 85012
United States, California
AIDS Healthcare Foundation
Los Angeles, California, United States, 02319
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States
United States, Massachusetts
Community Research Initiative of New England
Boston, Massachusetts, United States, 02215
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Sponsors and Collaborators
Community Research Initiative of New England
Investigators
Principal Investigator: Calvin J Cohen, MD, MSc CRI
  More Information

Additional Information:
No publications provided

Responsible Party: Cal Cohen, Director of Research, Community Research Initiative of New England
ClinicalTrials.gov Identifier: NCT00543101     History of Changes
Other Study ID Numbers: 07-142
Study First Received: October 11, 2007
Results First Received: April 12, 2010
Last Updated: February 9, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Community Research Initiative of New England:
HIV/AIDS
darunavir
Protease inhibitors
Dual boosted
Treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protease Inhibitors
Ritonavir
Darunavir
HIV Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014