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Optimizing Treatment for Treatment-Experienced, HIV-Infected People
This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), April 2009
First Received: September 27, 2007   Last Updated: April 22, 2009   History of Changes
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Adult AIDS Clinical Trials Group
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00537394
  Purpose

The goal of anti-HIV therapy is to prevent HIV from replicating. Long-term control of HIV requires at least two anti-HIV drugs that are active against the virus. Drug resistance is a problem for many treatment-experienced, HIV-infected people. The purpose of this study is to determine the benefit of adding a nucleoside reverse transcriptase inhibitor (NRTI) to a new anti-HIV drug regimen for the suppression of HIV.


Condition Intervention Phase
HIV Infections
Drug: Enfuvirtide
Drug: Raltegravir
Drug: Darunavir
Drug: Tipranavir
Drug: Etravirine
Drug: Maraviroc
Phase III

Study Type: Interventional
Study Design: Treatment, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title: The Optimized Treatment That Includes or Omit NRTIs Trial: A Randomized Strategy Study for HIV-1-Infected Treatment-Experienced Subjects Using the cPSS to Select an Effective Regimen

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Time to regimen failure [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity, as defined as time to first Grade 3 or higher (and one grade higher than baseline) signs/symptom or laboratory abnormality [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Tolerability, as defined as time to first dose modification, time to permanent discontinuation of all study drugs [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Time to abandoning randomized NRTI strategy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Time to virological failure, as defined by the protocol [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Binary variable indication if viral load is less than 50 copies/ml [ Time Frame: At Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]
  • Change in viral load [ Time Frame: From study entry to Week 1 ] [ Designated as safety issue: No ]
  • Binary variable indicating acquisition of drug resistance mutations to any of the study agents [ Time Frame: At time of virologic failure ] [ Designated as safety issue: No ]
  • Change in summarized quality of life score [ Time Frame: At study entry and Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]
  • Binomial indicator of "perfect" adherence to assigned ARVs [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change in cardiovascular risk score and fasting lipid values [ Time Frame: At Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]
  • Change in CD4 count [ Time Frame: From study entry to Week 96 ] [ Designated as safety issue: No ]
  • Time to serious non-AIDS events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Change in virus coreceptor tropism among those with R5-only tropic virus in Step 1 [ Time Frame: From study entry to time of virological failure and Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]
  • HIV-1 co-receptor tropism [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Binary indicator of undetectable CSF HIV-1 RNA [ Time Frame: At or after Week 24 ] [ Designated as safety issue: No ]
  • Summarized continuous neuro-cognitive performance Z-scores [ Time Frame: Through Week 96 ] [ Designated as safety issue: No ]
  • Binary variable indicating whether CSF ARV drug concentrations are above the population median [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • CPE score (CNS penetration effectiveness) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 577
Study Start Date: January 2008
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
Regimen with higher predicted activity assigned by the study plus at least 2 NRTIs assigned by the study for 96 weeks. A 3-4 drug regimen will be selected from the drugs listed to the right.
Drug: Enfuvirtide
One tablet twice daily
Drug: Raltegravir
400 mg twice daily
Drug: Darunavir
Two 300-mg tablets twice daily
Drug: Tipranavir
Two 250-mg capsules twice daily
Drug: Etravirine
Two 100-mg tablets twice daily
Drug: Maraviroc
Dosage dependent on regimen in which maraviroc is included
B: Experimental
Regimen with higher predicted activity assigned by the study without NRTIs for 96 weeks. A 3-4 drug regimen will be selected from the drugs listed to the right.
Drug: Enfuvirtide
One tablet twice daily
Drug: Raltegravir
400 mg twice daily
Drug: Darunavir
Two 300-mg tablets twice daily
Drug: Tipranavir
Two 250-mg capsules twice daily
Drug: Etravirine
Two 100-mg tablets twice daily
Drug: Maraviroc
Dosage dependent on regimen in which maraviroc is included
C: Active Comparator
Regimen with higher predicted activity assigned plus at least 2 NRTIs by the study for 96 weeks. A 3-4 drug regimen will be selected from the drugs listed to the right.
Drug: Enfuvirtide
One tablet twice daily
Drug: Raltegravir
400 mg twice daily
Drug: Darunavir
Two 300-mg tablets twice daily
Drug: Tipranavir
Two 250-mg capsules twice daily
Drug: Etravirine
Two 100-mg tablets twice daily
Drug: Maraviroc
Dosage dependent on regimen in which maraviroc is included

Detailed Description:

Two or more fully active antiretrovirals (ARVs) are recommended for successful suppression of HIV. In people infected with resistant HIV virus, finding two drugs that are fully active against HIV can be a challenge. However, the new generation of anti-HIV drugs has been designed to suppress drug-resistant HIV. These drugs include the FDA-approved protease inhibitors (PIs) darunavir and tipranavir, the investigational non-nucleoside transcriptase inhibitor (nNRTI) etravirine, the FDA-approved fusion inhibitor enfuvirtide, the recently FDA-approved CCR5 inhibitor maraviroc, and the investigational integrase inhibitor raltegravir. Also, it is not yet known whether multiple, partially-active drugs have the same rate of success in suppressing HIV. The purpose of this study is to use HIV resistance testing to predict the potency of a suggested ARV regimen using second generation ARVs and determine if the benefits of adding NRTIs to this new drug regimen outweigh the risks of drug toxicity and pill burden. All participants will have treatment experience or resistance to NRTIs, nNRTIs, and PIs, and who are receiving novel agents.

This study will have 2 steps and 3 arms. It will last for at least 75 days for all participants and will last an additional 96 weeks for those who continue to Step 2. In Step 1, all participants will remain on their current drug regimen. During this time, phenotypic and genotypic HIV resistance tests will be performed on participants' blood samples, as well as a coreceptor tropism assay. Using this information and medication history, the study team will determine the best new regimen options for each participant. Each clinician, along with the study participant, will then chose a new regimen based on the recommendations of the study team and the participant's preference.

Step 2 will begin when participants begin their new regimen. Stratification between Arms A and B or Arm C will be based on predicted activity of the new regimen. Those assigned to a regimen with higher predicted activity will be randomly assigned to Arm A or B; those assigned a regimen predicted to have lower activity will be assigned to Arm C.

Participants in Arms A and C will take their new assigned study regimen plus at least 2 NRTIs for 96 weeks. Participants in Arm B will take their new assigned study regimen with no NRTIs for 96 weeks. Participants in Arms A and B who reach virologic failure before 96 weeks will discontinue the study.

Participants in Arm C who reach virologic failure before 96 weeks will remain in the study.

All participants will have 11 clinical visits. At each visit, blood collection will occur. At some visits, urine collection and quality of life and adherence questionnaires will occur. A neurocognitive assessment will occur for all participants who enter Step 2. Participants may also consent to have cerebrospinal fluid collected via lumbar puncture upon entering Step 2 and/or at Week 24. Those participants who consent to cerebrospinal fluid collection will also have neurocognitive assessments at the times of collections. Participants will be responsible for obtaining certain ARVs not provided by the study, including the ARVs they take in Step 1 and depending on which arm of Step 2 they are in.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Step 1:

  • HIV-1 infection
  • Triple-class drug experience or resistance. More information on this criterion can be found in the protocol.
  • Currently on a failing PI-containing regimen that includes 2 other ARVs with no regimen change for 8 weeks prior to study screening
  • HIV viral load of 1000 copies/ml or more
  • Hepatitis B surface antigen negative within 90 days of study entry
  • Able to obtain NRTIs and ritonavir and have required ARVs at time of entry to Step 2
  • Willing to use acceptable forms of contraception
  • Parent or legal guardian willing to provide consent, if applicable
  • CD4 count result from a specimen drawn within 120 days prior to study entry
  • If any previous HIV-1 viral co-receptor tropism result is available, then most recent specimen date and the tropism result of that specimen AND specimen date and tropism result of any test with either X4 or D/M result, if different from the first specimen, must be available

Inclusion Criteria for Step 2:

  • Receipt of successful phenotype/genotype resistance results within 105 days prior to entry into Step 2
  • Study team identification of a study regimen and at least 2 NRTIs for participant to take in Step 2
  • Currently on the same failing PI-containing regimen for the entire duration of Step 1 that includes at least 2 other ARVs besides the PI
  • Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
  • Willing to use accepted forms of contraception

Exclusion Criteria for Step 1:

  • Chronic, active hepatitis B virus infection (hepatitis B surface antigen positive or HBV DNA positive)
  • Prior use of any integrase inhibitor
  • Taking certain medications. More information on this criterion can be found in the protocol.
  • Known allergy/sensitivity to components of two or more of the study-provided drugs or their formulations. For maraviroc, this includes hypersensitivity or history of allergy to soy lecithin or peanuts.
  • Active drug or alcohol use that, in the opinion of the investigator, may interfere with the study
  • Pregnancy or breastfeeding

Exclusion Criteria for Step 2:

  • Has participated for 76 days or more in Step 1
  • Use of any immunomodulator (interferons, interleukins, systemic corticosteroids, or cyclosporine), vaccine, or investigational therapy within 30 days of entry to Step 2
  • Require certain medications prohibited with study treatment
  • Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to Step 2 entry are not excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00537394

Locations
United States, California
USC, ACTU Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Luis M. Mendez     323-343-8283     lmendez@usc.edu    
Principal Investigator: Fred R. Sattler, MD            
UCDF PHP, San Francisco General Hospital Not yet recruiting
San Francisco, California, United States, 94110
Contact: Michele Downing, RN, BSN     415-514-0550 ext 354     mdowning@php.ucsf.edu    
Principal Investigator: Diane Havlir, MD            
Ucsd, Avrc Crs Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkel, RN     619-543-8080     jkunkel@ucsd.edu    
Principal Investigator: Constance A. Benson, MD            
Harbor UCLA Medical Center NICHD CRS Recruiting
Torrance, California, United States, 90502
Contact: Judy Hayes, BSN, RN     310-781-3627     jhayes@labiomed.org    
Principal Investigator: Margaret Keller, MD            
United States, Colorado
University of Colorado Hospital CRS Recruiting
Aorora, Colorado, United States, 80045
Contact: Mary Graham Ray, RN     303-724-0712     graham.ray@uchsc.edu    
Principal Investigator: Thomas B. Campbell, MD            
United States, District of Columbia
Howard University Hospital Recruiting
Washington, District of Columbia, United States, 20060
Contact: Patricia H. Yu, MS     313-745-9204     uhancock@dmc.org    
Principal Investigator: Ellen C. Moore, MD            
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Karyn Hawkins, RN     202-687-2294     hawkinsk@georgetown.edu    
Principal Investigator: Princy N. Kumar, MD            
United States, Illinois
Rush University Medical Center ACTG Recruiting
Chivago, Illinois, United States, 60612
Contact: Jan Fritsche, MS, RN     312-942-4810     jfrits@rush.edu    
Principal Investigator: Beverly E. Sha, MD            
Chicago Children's CRS Recruiting
Chicago, Illinois, United States, 60614
Contact: Eric Cagwin, RN     773-880-3669     ECagwin@childrensmemorial.org    
Principal Investigator: Ram Yogev, MD            
United States, Maryland
University of Maryland Biotechnology Institute, Inst of Human Virology Not yet recruiting
Baltimore, Maryland, United States, 21201
Contact: Sandy Zaremba, RN, CCRC     410-706-1476     szaremba@ihv.umaryland.edu    
Principal Investigator: Robert R. Redfield, MD            
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Neah S. Kim, MSN, APRN, FNP     617-632-7627     nkim@bidmc.harvard.edu    
Principal Investigator: Mary Albrecht, MD            
Boston Medical Center ACTG Recruiting
Boston, Massachusetts, United States, 02118
Contact: Betsy Adams, RN     617-414-7082     betsy.adams@bmc.org    
Principal Investigator: Paul R. Skolnik, MD            
Boston Medical Center Pediatric HIV Program Recruiting
Boston, Massachusetts, United States, 02118
Contact: Laureen Kay, RN     617-414-3632     laureen.kay@bmc.org    
Principal Investigator: Stephen Ira Pelton, MD            
United States, New York
Univ. of Rochester Med. Ctr., Div. of Infectious Disease Recruiting
Rochester, New York, United States, 14642
Contact: Carol Greisberger, RN, BS     585-275-2740     carol_greisberger@urmc.rochester.edu    
Principal Investigator: Richard C. Reichman, MD            
AIDS Community Health Center Not yet recruiting
Rochester, New York, United States, 14642
Contact: Carol Greisberger, RN, BS     585-275-2740     carol_greisberger@urmc.rochester.edu    
Principal Investigator: Richard C. Reichman, MD            
Weill Medical College of Cornell University, The Cornell CTY - Chelsea Not yet recruiting
New York, New York, United States, 10011
Contact: Todd Stroberg, RN     212-746-7198     tstrober@med.cornell.edu    
Principal Investigator: Marshall Jay Glesby, MD, PhD            
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Brett Gray, MPH     212-305-3180     bg2168@columbia.edu    
Principal Investigator: Scott M. Hammer, MD            
United States, North Carolina
The Moses H. Cone Memorial Hospital, Internal Medicine Training Program Not yet recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, RN     336-832-7888     kim.epperson@mosescone.com    
Principal Investigator: Timothy W. Lane, MD            
Duke University Medical Center - Pediatric CRS Recruiting
Durham, North Carolina, United States, 27710
Contact: John Swetnam     919-668-4847     swetnam@acpub.duke.edu    
Principal Investigator: Coleen Cunningham, MD            
United States, Ohio
University of Cincinnati, Division of Infectious Diseases Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Tammy Powell, RN     513-584-8373     powelltm@email.uc.edu    
Principal Investigator: Carl J. Finchtenbaum, MD            
United States, Tennessee
Vanderbilt Therapeutics CRS Recruiting
Nashville, Tennessee, United States, 37203
Contact: Janet Nicotera, RN, BSN     615-467-0154 ext 108     janet.nicotera@vanderbilt.edu    
Principal Investigator: David W. Haas, MD            
St. Jude/UTHSC CRS Recruiting
Memphis, Tennessee, United States, 38105
Contact: Laura Jill Utech, RN, MSN     901-495-3490     jill.utech@stjude.org    
Principal Investigator: Patricia M. Flynn, MD            
United States, Texas
Thomas Street Clinic CRS Recruiting
Houston, Texas, United States, 77030
Contact: Hilda Cuervo     713-500-6751     Hilda.Cuervo@uth.tmc.edu    
Principal Investigator: Roberto C. Arduino, MD            
Texas Children's Hosp. CRS Not yet recruiting
Houston, Texas, United States, 77030
Contact: Chivon D. Jackson, BSN, ADN     832-824-1339     cdmcmull@texaschildrenshospital.org    
Principal Investigator: William T. Shearer, MD, PhD            
Puerto Rico
San Juan City Hospital Recruiting
San Juan, Puerto Rico
Contact: Maria del Pilar Thurin, MPH     (787) 765-4186     actg.pedsjch@fstrf.org    
Principal Investigator: Midnela Acevedo, MD            
Sponsors and Collaborators
Adult AIDS Clinical Trials Group
Investigators
Study Chair: Karen T. Tashima, MD Brown University
Study Chair: Richard H. Haubrich, MD Division of Infectious Diseases, UCSD Antiviral Research Center
  More Information

Additional Information:
Publications:
Responsible Party: DAIDS ( Rona Siskind )
Study ID Numbers: ACTG A5241, OPTIONS
Study First Received: September 27, 2007
Last Updated: April 22, 2009
ClinicalTrials.gov Identifier: NCT00537394     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced

Study placed in the following topic categories:
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Darunavir
Enfuvirtide
Tipranavir
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Retroviridae Infections
HIV Fusion Inhibitors

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

ClinicalTrials.gov processed this record on July 06, 2009