HIV-1 InfectionsPhase 3ICE-002NCT00984152
Trial of TDF/FTC + Raltegravir Versus TDF/FTC + Efavirenz in HIV-1-Infected Women
A Phase 3 study testing TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily and TDF/FTC + Efavirenz (Atripla) Once-Daily in people with HIV-1 Infections, run by Rush University Medical Center at 5 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- HIV-1 Infections
- What is being tested?
- TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily and TDF/FTC + Efavirenz (Atripla) Once-Daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2011to Dec 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
- 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.
- Female sex, Age > 18 and < 60 years, Pre-menopausal.
- 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.
- The absence of exclusionary resistance mutations on a genotypic resistance assay (absence of exclusionary NRTI or NNRTI resistance mutations by genotype testing)
- Antiretroviral (ARV) drug-naïve (defined as 7 days of ARV treatment at any time prior to entry).
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- 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)
- 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
- Contraception requirements for women who have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
- 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.
Who cannot join
- Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy
- Any active infection, including co-infection with hepatitis B or C
- Any neoplasm
- Immunosuppressive therapy
- Requirement for any medications that are prohibited by any of the study treatments
- Significant liver or renal dysfunction
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- 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
- Alcohol or substance abuse problems or psychiatric conditions that impair the ability of the subject to comply with the study protocol
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Mt. Sinai Hospital
Chicago, Illinois, 60608
Rush University Medical Center
Chicago, Illinois, 60612
University of Illinois at Chicago
Chicago, Illinois, 60612
The Ruth M. Rothstein CORE Center (of Cook County)
Chicago, Illinois, 60622
University of Chicago
Chicago, Illinois, 60637
About this study
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
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:
Read more
- Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization).
- Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract.
- 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.
Read the 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.
- Conditions
- HIV-1 Infections
- Being tested
- TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily, TDF/FTC + Efavirenz (Atripla) Once-Daily
- Keywords
- HIV, Raltegravir, Women, Viral Suppression, Viral Reservoir, Immune Parameters, Gut, Genital Tract
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-DailyDrug
Also called TDF/FTC Once-Daily + Raltegravir (Isentress) 400 mg Orally Twice-Daily
TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
TDF/FTC + Efavirenz (Atripla) Once-DailyDrug
TDF/FTC + Efavirenz (Atripla) Once-Daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily Receives: Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily |
| 2 | Active comparator | TDF/FTC + Efavirenz (Atripla) Once-Daily Receives: Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization)
Measured: 48 weeks
Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract
Measured: 48 weeks
Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles
Measured: 48 weeks
Secondary outcomes (1)
Determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2009 (estimated)
- Study startJun 2011
- Primary completionJun 2013 (estimated)
- Study completionDec 2013 (estimated)
Why it stopped: Decision not to go forth with study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1 InfectionsStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Investigators
- Alan L. Landay, Ph.D., Principal investigator, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984152
- Sponsor's protocol ID
- 08102303-IRB01
- Other IDs
- Merck IISP #33421
- Acronym
- ICE-002
- Status last verified
- May 2015
- First submitted
- 7 May 2009
- Last updated
- 6 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00984152
- Acronym / sponsor ID
- ICE-002 / 08102303-IRB01
- Conditions
- HIV-1 Infections
- Keywords
- HIV, Raltegravir, Women, Viral Suppression, Viral Reservoir, Immune Parameters, Gut, Genital Tract
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Decision not to go forth with study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2011
- Primary completion
- Jun 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 25 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization).
- Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract.
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-DailyTDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily |
| 2 | Active comparator | Drug: TDF/FTC + Efavirenz (Atripla) Once-DailyTDF/FTC + Efavirenz (Atripla) Once-Daily |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- 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.
- 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.
- Female sex, Age > 18 and < 60 years, Pre-menopausal.
- 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.
- The absence of exclusionary resistance mutations on a genotypic resistance assay (absence of exclusionary NRTI or NNRTI resistance mutations by genotype testing)
Key exclusion criteria (10 listed)
- Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy
- Any active infection, including co-infection with hepatitis B or C
- Any neoplasm
- Immunosuppressive therapy
- Requirement for any medications that are prohibited by any of the study treatments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-DailyAlso: TDF/FTC Once-Daily + Raltegravir (Isentress) 400 mg Orally Twice-DailyTDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily | Drug | 1 |
| TDF/FTC + Efavirenz (Atripla) Once-DailyTDF/FTC + Efavirenz (Atripla) Once-Daily | Drug | 2 |
Primary outcome
Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization)
Time frame: 48 weeks
Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract
Time frame: 48 weeks
Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles
Time frame: 48 weeks
1 secondary outcome
Determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz
Time frame: 48 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan L. Landay, Ph.D. principal investigator
Rush University Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily and TDF/FTC + Efavirenz (Atripla) Once-Daily in people with HIV-1 Infections, run by Rush University Medical Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization) (time frame: 48 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2015.