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

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01352715
First received: January 12, 2011
Last updated: December 2, 2015
Last verified: December 2015
  Purpose

The study was conducted on people who were 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 were not doing a good job of fighting their HIV infection.

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

The study was designed to determine whether taking the combination of lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) works as well as what is usually 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 NRTIs was 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:
  • Cumulative Probability of Virologic Failure by Week 48 [ Time Frame: From study entry to week 48 ] [ Designated as safety issue: No ]
    The primary endpoint was time to virologic failure. Virologic failure was defined as confirmed viral load >400 copies/mL at or after week 24. The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 48 was used.


Secondary Outcome Measures:
  • Change in CD4+ Cell Count From Baseline to Week 48 [ Time Frame: Study entry and week 48 ] [ Designated as safety issue: No ]
    Change in CD4+ cell count was calculated as CD4+ cell count at week 48 minus CD4+ cell count at study entry.

  • Number of Participants With HIV-1 Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase in Participants With Virologic Failure at Baseline and at Time of Virologic Failure [ Time Frame: From study entry through to week 96 ] [ Designated as safety issue: No ]
    Mutations were defined as major IAS mutations in the IAS-USA July 2014 list. New mutations were those detected at virologic failure but not at baseline.

  • Number of Participants With Grade 3 or Higher Adverse Event (AE) at Least One Grade Higher Than Baseline [ Time Frame: From start of randomized treatment to off randomized treatment (up to 96 weeks) ] [ Designated as safety issue: Yes ]
    The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

  • Number of Participants Discontinuing Randomized Treatment for Toxicity [ Time Frame: From Start of Randomized Treatment to Off Randomized Treatment (up to 96 weeks) ] [ Designated as safety issue: Yes ]
    Discontinuation of randomized treatment for toxicity included participant decision to discontinue for low grade toxicity. Within class NRTI changes were not considered discontinuations.

  • Number of Participants With a New AIDS-defining Events or Death [ Time Frame: From study entry throughout follow-up (up to 96 weeks) ] [ Designated as safety issue: No ]
    AIDS-defining events were those recognized by the Centers for Disease Control (CDC) and World Health Organization (WHO)

  • Number of Participants With a Targeted Serious Non-AIDS-defining Event or Death [ Time Frame: From study entry throughout follow-up (up to 96 weeks) ] [ Designated as safety issue: No ]
    Serious non-AIDS diagnoses were based on ACTG Appendix 60 Diagnosis Codes

  • Percentage of Time Spent in Hospital [ Time Frame: From study entry throughout follow-up (up to 96 weeks) ] [ Designated as safety issue: No ]
    The percentage of total study time that participants were in hospital.

  • Changes in Fasting Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides, and Glucose From Baseline [ Time Frame: Study entry and week 48 ] [ Designated as safety issue: No ]
    Fasting was for 8 hours and the metabolic panel was drawn locally.


Enrollment: 515
Study Start Date: January 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: LPV/r plus RAL
Participants were administered LPV/r plus RAL orally twice daily throughout 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, throughout follow-up.
Other Names:
  • Aluvia
  • LPV/r
  • Kaletra
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, throughout follow-up.
Other Names:
  • Kaletra
  • LPV/r
Drug: Raltegravir
Raltegravir 400 mg tablet orally twice daily, with or without food, throughout follow-up.
Other Names:
  • Isentress
  • RAL
Experimental: Arm B: LPV/r plus best available NRTIs

Participants were administered LPV/r orally twice daily, plus NRTI options provided by the study, to include the best available NRTIs (listed below) throughout 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 two LPV 200mg/RTV 50mg fixed-dose combination tablets) orally twice daily, with or without food, throughout follow-up.
Other Names:
  • Aluvia
  • LPV/r
  • Kaletra
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, throughout follow-up.
Other Names:
  • Kaletra
  • LPV/r
Drug: Emtricitabine/tenofovir disoproxil fumarate
Emtricitabine 200 mg/tenofovir disoproxil fumarate 300mg fixed-dose combination tablet orally once daily, with or without food, throughout 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, throughout 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, throughout 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, throughout 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, throughout follow-up.
Other Names:
  • Ziagen
  • ABC
Drug: Zidovudine
Zidovudine 300 mg tablet orally twice daily, with or without food, throughout follow-up.
Other Names:
  • Retrovir
  • ZDV
Drug: Lamivudine
Lamivudine 150 mg tablet orally twice daily, with or without food, throughout 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
Brazil
Instituto de Pesquisa Clinica Evandro Chagas (12101)
Rio de Janeiro, Brazil, 21045
India
BJ Medical College CRS (31441)
Pune, Maharashtra, India, 411001
NARI Pune CRS
Pune, Maharashtra, India
Y.R.G Ctr, for AIDS Research and Education (11701)
Chennai, India
Kenya
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
Eldoret, Kenya, 30100
Malawi
College of Med. JHU CRS (30301)
Blantyre, Malawi
University of North Carolina Lilongwe CRS (12001)
Lilongwe, Malawi
Peru
San Miguel CRS
San Miguel, Lima, Peru
Barranco CRS (11301)
Lima, Peru, 18 PE
South Africa
Wits HIV CRS (11101)
Johannesburg, Gauteng, South Africa
Durban Adult HIV CRS (11201)
Durban, South Africa, 4013 SF
Soweto ACTG CRS (12301)
Johannesburg, South Africa
Univ. of Witwatersrand CRS (11101)
Johannesburg, South Africa
Tanzania
Kilimanjaro Christian Medical CRS
Kilimanjaro Region, Moshi, Tanzania
Thailand
Chiang Mai University ACTG CRS (11501)
Chiang Mai, Thailand, 50202
Zimbabwe
UZ-Parirenyatwa CRS (30313)
Harare, Zimbabwe
Sponsors and Collaborators
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
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  5UM1AI068634 
Study First Received: January 12, 2011
Results First Received: October 29, 2015
Last Updated: December 2, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Abacavir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Lamivudine
Lamivudine, zidovudine drug combination
Lopinavir
Ritonavir
Tenofovir
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Protease Inhibitors
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on May 24, 2016