Trial of TDF/FTC + Raltegravir Versus TDF/FTC + Efavirenz in HIV-1-Infected Women (ICE-002)

This study has been withdrawn prior to enrollment.
(Decision not to go forth with study.)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT00984152
First received: May 7, 2009
Last updated: May 4, 2011
Last verified: May 2011
  Purpose

Raltegravir not only has a unique mechanism of action, but may also have other unique effects on suppression of viral replication, viral reservoir, and immune reconstitution in blood and other important compartments. This may in part be due to the pharmacokinetics of Raltegravir in blood and gut tissue. Efavirenz will be the comparator antiretroviral drug in this study, with both drugs being used as part of a three-drug regimen with tenofovir and emtricitabine.

The primary objectives are to determine differences in the effects of 2 anti-retroviral regimens, Raltegravir + Truvada versus Atripla, with respect to:

  1. Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization).
  2. Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract.
  3. Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles.

The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz.


Condition Intervention Phase
HIV-1 Infections
Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Randomized Trial of TDF/FTC+Raltegravir Vs. TDF/FTC+Efavirenz in HIV-1-Infected Women: Differential Effects on Viral Suppression/Reservoir, & Immune Parameters in Different Compartments, Including Gut & Genital Tract

Resource links provided by NLM:


Further study details as provided by Rush University Medical Center:

Primary Outcome Measures:
  • Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: June 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
Other Name: TDF/FTC Once-Daily + Raltegravir (Isentress) 400 mg Orally Twice-Daily
Active Comparator: 2
TDF/FTC + Efavirenz (Atripla) Once-Daily
Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily
TDF/FTC + Efavirenz (Atripla) Once-Daily
Other Name: TDF/FTC + Efavirenz (Atripla) Once-Daily

Detailed Description:

This is a phase III, prospective, randomized (1:1), multicenter, open label study comparing the effects of two HAART regimens:

  • Arm A: Raltegravir 400 mg PO BID + TDF/FTC (Truvada, 300/200 mg) One PO Daily
  • Arm B: Efavirenz + TDF/FTC (Atripla) Once PO Daily

The following local sites: Mt. Sinai, Rush University Medical Center, Stroger Hospital, University of Chicago and University of Illinois will work together to enroll 10 eligible women meeting all eligibility criteria (5 per study arm) over a one year time period. These 10 women will be randomized 1:1 to receive either TDF/FTC + Raltegravir or TDF/FTC + Efavirenz (Atripla). There will be 2 baseline evaluations prior to initiation of study therapy. Subjects will be followed for 48 weeks after initiation of study treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Eligible subjects will be antiretroviral naïve (< 7 days of HAART at any time prior to entry) with plasma HIV-1 RNA > 50,000 copies/mL (obtained within 90 days prior to study entry by any laboratory that has a CLIA certification or its equivalent) and moderate immune suppression within 90 days prior to study entry.
  2. HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test. Alternatively, if a licensed ELISA is not available, two HIV-1 RNA values >2000 copies/mL at least 24 hours apart performed by any laboratory that has CLIA certification or its equivalent may be used to document infection.
  3. Female sex, Age > 18 and < 60 years, Pre-menopausal.
  4. Screening CD4+ T-cell count between 200-350 cells/mm3 obtained within 90 days prior to study entry by any laboratory that has a CLIA certification or its equivalent.
  5. The absence of exclusionary resistance mutations on a genotypic resistance assay (absence of exclusionary NRTI or NNRTI resistance mutations by genotype testing)
  6. Antiretroviral (ARV) drug-naïve (defined as 7 days of ARV treatment at any time prior to entry).
  7. Laboratory values obtained within 45 days prior to study entry:

    • Absolute neutrophil count (ANC) 500/mm3
    • Hemoglobin 8.0 g/dL
    • Platelet count 40,000/mm3
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase 5 ULN
    • Total bilirubin 2.5 x ULN
    • Calculated creatinine clearance ≥60 mL/min as estimated by the Cockcroft-Gault equation:

      • For women, multiply the result by 0.85 = CrCl (mL/min)
  8. Negative serum or urine pregnancy test within 48 hours prior to initiating study medications unless otherwise specified by product labeling.

    • Female candidates of reproductive potential is defined as women who have had regular menses over the preceding 24 months
  9. Contraception requirements for women who have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
  10. Female candidates of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to the following:

    • If the regimen does not include EFV, they must agree to use at least one reliable method of contraception while receiving the protocol-specified drugs and for 6 weeks after stopping the medications.
    • If the regimen includes EFV, they must agree to use two reliable methods of contraception: a barrier method of contraception (e.g., condoms, diaphragm, or cervical cap with or without spermicide) together with another reliable form of contraceptive (e.g., a second barrier method, an IUD, or a hormone-based contraceptive) while receiving EFV and for 6 weeks after stopping EFV.

Exclusion Criteria:

  1. Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy
  2. Any active infection, including co-infection with hepatitis B or C
  3. Any neoplasm
  4. Immunosuppressive therapy
  5. Requirement for any medications that are prohibited by any of the study treatments
  6. Significant liver or renal dysfunction
  7. Baseline resistance to any of the study drugs by genotypic testing

    • NRTI: M41L, K65 R, D76N, T69D, K70R, L74V/I, y115F, Q151M, M184V, L210W, T215any, K219Q/E
    • NNRTI:L100I, K103N, V106A/M, V108I, Y181C/I, Y188C/L/H, G190anyA/S
  8. Alcohol or substance abuse problems or psychiatric conditions that impair the ability of the subject to comply with the study protocol
  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: NCT00984152

Locations
United States, Illinois
Mt. Sinai Hospital
Chicago, Illinois, United States, 60608
University of Chicago
Chicago, Illinois, United States, 60637
Rush University Medical Center
Chicago, Illinois, United States, 60612
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
The Ruth M. Rothstein CORE Center (of Cook County)
Chicago, Illinois, United States, 60622
Sponsors and Collaborators
Rush University Medical Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Alan L. Landay, Ph.D. Rush University Medical Center
  More Information

No publications provided

Responsible Party: Alan L. Landay, Ph.D., Rush University Medical Center
ClinicalTrials.gov Identifier: NCT00984152     History of Changes
Other Study ID Numbers: 08102303-IRB01, Merck IISP #33421
Study First Received: May 7, 2009
Last Updated: May 4, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Rush University Medical Center:
HIV
Raltegravir
Women
Viral Suppression
Viral Reservoir
Immune Parameters
Gut
Genital Tract

Additional relevant MeSH terms:
Efavirenz
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014