Study of Options for Second-Line Effective Combination Therapy (SELECT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01352715
First received: January 12, 2011
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

The study is being done with people who are taking their first anti-HIV drug regimen (including an Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), a type of anti-HIV drug) but the drugs in this regimen are not doing a good job of fighting their HIV infection.

The main purpose of this study is to compare two other anti-HIV drug regimens to see how well they fight HIV. The study will also see how well participants tolerate the drug regimens and how safe they are.

The study will determine whether taking the combination of lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) works as well as what usually is used for second-line therapy: LPV/r plus the best-available nucleoside (nucleotide) reverse transcriptase inhibitor (NRTI) combination. Testing a regimen that does not include any NRTI is important because NRTIs may no longer work for patients who received them as part of their first treatment regimen.


Condition Intervention Phase
HIV-1 Infection
Drug: Lopinavir/ritonavir
Drug: Raltegravir
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Abacavir/lamivudine/zidovudine
Drug: Abacavir/lamivudine
Drug: Lamivudine/zidovudine
Drug: Abacavir
Drug: Zidovudine
Drug: Lamivudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Study of Options for Second-Line Effective Combination Therapy (SELECT)

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Time to virologic failure [ Time Frame: At or after study Week 24 ] [ Designated as safety issue: No ]
    The primary endpoint is time to virologic failure. Virologic failure is defined as confirmed viral load >400 copies/mL at or after week 24.


Secondary Outcome Measures:
  • Change in CD4+ cell count from baseline [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]
    CD4+ cell count at baseline, weeks 48, 96 and at virologic failure

  • HIV-1 drug resistance mutations in gag, protease, reverse transcriptase, and integrase in participants with virologic failure at baseline and at time of virologic failure [ Time Frame: Through to week 96 ] [ Designated as safety issue: No ]
  • Time to first Grade 3 or higher Adverse Event (AE) that is at least one grade higher than baseline [ Time Frame: Through to week 96 ] [ Designated as safety issue: Yes ]
  • Time to discontinuation of randomized treatment for toxicity [ Time Frame: Through to week 96 ] [ Designated as safety issue: Yes ]
    Time to discontinuation of randomized treatment for toxicity (including participant decision to discontinue for low grade toxicity); within class NRTI changes are not considered an endpoint.

  • Time to new AIDS-defining events, death and targeted serious non-AIDS-defining events [ Time Frame: Through to week 96 ] [ Designated as safety issue: Yes ]
  • Duration of hospitalizations [ Time Frame: Through to week 96 ] [ Designated as safety issue: No ]
  • Changes in fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and glucose from baseline [ Time Frame: Weeks 48 and 96 ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: January 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: LPV/r plus RAL
Participants will be administered LPV/r plus RAL orally twice daily until the participant reaches 96 weeks of follow-up.
Drug: Lopinavir/ritonavir
Lopinavir 400mg/ritonavir 100mg (given as two LPV 200mg/RTV 50mg fixed-dose combination tablets) orally twice daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Aluvia
  • LPV/r
  • Kaletra
Experimental: Arm B: LPV/r plus best available NRTIs

Participants will be administered LPV/r orally twice daily, plus NRTI options provided by the study, to include the best available NRTIs (listed below) until the participant reaches 96 weeks of follow-up-

  • FTC/TDF orally twice daily
  • ABC/3TC/ZDV orally twice daily
  • ABC/3TC orally once daily
  • 3TC/ZDV orally twice daily
  • ABC 300mg orally twice daily or 600 mg once daily
  • 3TC orally twice daily
  • ZDV orally twice daily
Drug: Lopinavir/ritonavir
Lopinavir 400mg/ritonavir 100mg (given as three LPV 133.3 mg/RTV 33.3 mg fixed-dose combination soft gelatin capsules) orally twice daily, with food until the participant reaches 96 weeks of follow-up.
Other Names:
  • Kaletra
  • LPV/r
Drug: Raltegravir
Raltegravir 400 mg tablet orally twice daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Isentress
  • RAL
Drug: Emtricitabine/tenofovir disoproxil fumarate
Emtricitabine 200 mg/tenofovir disoproxil fumarate 300mg fixed-dose combination tablet orally once daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Truvada
  • FTC/TDF
Drug: Abacavir/lamivudine/zidovudine
Abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet orally twice daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Trizivir
  • ABC/3TC/ZDV
Drug: Abacavir/lamivudine
Abacavir 600 mg/lamivudine 300 mg fixed-dose combination tablet orally once daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Epzicom
  • ABC/3TC
Drug: Lamivudine/zidovudine
Lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet orally twice daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Combivir
  • CBV
  • 3TC/ZDV
Drug: Abacavir
Abacavir 300 mg tablet orally twice daily or 600 mg (given as two 300 mg tablets) once daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Ziagen
  • ABC
Drug: Zidovudine
Zidovudine 300 mg tablet orally twice daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Retrovir
  • ZDV
Drug: Lamivudine
Lamivudine 150 mg tablet orally twice daily, with or without food, until the participant reaches 96 weeks of follow-up.
Other Names:
  • Epivir
  • 3TC

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected
  • Confirmation of first-line virologic failure
  • Certain laboratory values obtained within 45 days prior to study entry. More information on this criterion can be found in the study protocol.
  • Negative pregnancy test within 48 hours prior to study entry.
  • Must refrain from participating in a conception process, and, if participating in sexual activity that could lead to pregnancy, must use at least one acceptable type of contraceptive. More information on this criterion can be found in the study protocol.
  • Karnofsky performance score >/= 70 within 45 days prior to study entry.
  • Ability and willingness of participant or legal guardian/representative to provide informed consent.
  • No intention to relocate away from current geographical area of residence for the duration of study participation.

Exclusion Criteria:

  • Use of any immunomodulator, HIV vaccine, or other investigational therapy within 45 days prior to study entry, with the exception of a tapering course of corticosteroids as acute therapy for pneumocystis jiroveci pneumonia (PCP) or acute asthma/chronic obstructive pulmonary disease flare and/or prednisone at a daily dose of <10 mg (physiologic replacement dose).
  • If the potential participant has had resistance testing, evidence of broad NRTI cross-resistance that, in the opinion of the investigator, would not allow selection of an effective NRTI combination if the participant were randomized to the LPV/r + best available NRTIs arm.
  • Prior exposure to a Protease Inhibitor.
  • Known history of congenital long QT syndrome, hypokalemia, or planned use of other drugs that prolong the QT interval.
  • Pregnancy or breast-feeding.
  • Known history of chronic hepatitis B virus (HBV) infection or current HBV infection defined by the presence of hepatitis B surface antigen in serum or plasma.
  • Active tuberculosis (TB) requiring treatment with rifampicin.
  • Previously diagnosed malignancies other than basal cell carcinoma and cutaneous Kaposi sarcoma.
  • Requirement for taking any medications that are prohibited with the study drugs. More information on this criterion can be found in the study protocol, section 5.4.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  • Active drug or alcohol use or dependence or other condition that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
  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: NCT01352715

Locations
Malawi
University of North Carolina Lilongwe CRS (12001)
Lilongwe, Malawi
South Africa
Soweto ACTG CRS (12301)
Johannesburg, South Africa
Univ. of Witwatersrand CRS (11101)
Johannesburg, South Africa
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Alberto M La Rosa, MD Asociacion Civil Impacta Salud y Educacion - Miraflores, CRS
Study Chair: Ann C Collier, MD Univ. of Washington Clinical HIV Research Program (CHIRP)
  More Information

Publications:
[1] Hull M, Moore D, Harris M, et al. A lamivudine (3TC)-based backbone in conjunction with a boosted protease inhibitor (PI) is sufficient to achieve virologic suppression in the presence of M184V mutations. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12-15, 2009; San Francisco, California. Abstract H-916.

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01352715     History of Changes
Other Study ID Numbers: ACTG A5273, 1U01AI068636
Study First Received: January 12, 2011
Last Updated: January 28, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Ritonavir
Lopinavir
Tenofovir
Tenofovir disoproxil
Lamivudine
Zidovudine
Abacavir
Lamivudine, zidovudine drug combination
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites

ClinicalTrials.gov processed this record on September 16, 2014