Study of Lopinavir/ Ritonavir and Lamivudine Versus Standard Therapy in Naïve HIV-1 Infected Subjects. (GARDEL)

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Pedro Cahn, The Huesped Foundation
ClinicalTrials.gov Identifier:
NCT01237444
First received: November 8, 2010
Last updated: June 8, 2012
Last verified: June 2012
  Purpose

The purpose of this study is designed to compare the safety, tolerability, antiviral activity and immunological effect of lopinavir/ritonavir plus lamivudine (3TC) versus standard therapy with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus lopinavir/ritonavir in the treatment of naïve HIV-1 infected subjects.


Condition Intervention Phase
HIV Infection
Drug: lopinavir/ritonavir plus one nucleoside
Drug: lopinavir /ritonavir plus two nucleosides
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: A Phase 3, Randomized, Open Label, Controlled Study of Lopinavir/Ritonavir and Lamivudine Versus Standard Therapy in Naïve HIV-1 Infected Subjects.

Resource links provided by NLM:


Further study details as provided by The Huesped Foundation:

Primary Outcome Measures:
  • • Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL in an intent-to-treat analysis at week 48 [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • Proportion of patients with HIV-1 RNA levels of less than 400 copies/mL at week 24 and at week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    • Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at week 24.
    • Number and type of resistance mutations in case of virologic failure• CD4+ lymphocyte count and proportion evolution between baseline and week 24 and 48.
    • Comparison of lipid profiles after 48 weeks
    • Changes in quality of life, assessed by a validated questionnaire
    • Treatment survival and interruptions.
    • Frequency, type and severity of adverse events.
    • Frequency of opportunistic infections (OI) and disease progression.


Enrollment: 417
Study Start Date: December 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lopinavir/ritonavir plus lamivudine

ARM 1:

Lopinavir/ritonavir 200mg/50mg 2 tabs bid plus 3TC 150mg x1 tab bid

Drug: lopinavir/ritonavir plus one nucleoside

ARM 1:

Lopinavir/ritonavir 200mg/50mg 2 tabs bid plus 3TC 150mg x1 tab bid

Active Comparator: lopinavir/ritonavir plus two nucleosides

ARM 2:

3TC 150mg x1 tab bid or FTC 200mg 1 capsule qd plus Lopinavir/ritonavir 200mg/50mg 2 tabs BID plus a second NRTI, selected at investigator's discretion, based on baseline genotype

Drug: lopinavir /ritonavir plus two nucleosides

ARM 2:

3TC 150mg x1 tab bid or FTC 200mg 1 capsule qd plus Lopinavir/ritonavir 200mg/50mg 2 tabs BID plus a second NRTI, selected at investigator's discretion, based on baseline genotype.


Detailed Description:

Combination therapy with 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) has been the mainstay of therapy for over 10 years, based on sound evidence derived from randomized controlled clinical trials and epidemiological data.A variety of new approaches designed to address the problems associated with combination highly active antiretroviral therapy (HAART) are currently being explored. These include strategic treatment interruptions to reduce time on therapy, toxicity and cost;Based on its performance, a dual drug combination that includes lopinavir/ritonavir and spares the more toxic NRTIs such as thymidine nucleoside-analogs, but maintains non-thymidine nucleoside-analogs appears as a potentially simple, safe and effective regimen.

  Eligibility

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

Inclusion Criteria:

  1. > 18 years of age.
  2. Patient with documented HIV-1 infection
  3. Subject has voluntarily signed and dated an informed consent form
  4. Subject agrees not to take any medication during the study, including over the counter medicines or herbal preparations, without the approval of the trial physician.
  5. Documented HIV-1 RNA >1,000 copies/mL
  6. Subject naïve to ARV. (Patients who had received ARV ≤ 48 hours are allowed).
  7. Subject has indication to receive an antiretroviral regimen.
  8. Subjects can comply with protocol requirements.
  9. Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the trial.
  10. If female, :

    1. use 2 different methods of birth control including, at least, one barrier method, and are acceptable to both the subject and investigator, and
    2. has a urine pregnancy test performed at the Screening Visit and on Baseline. Results of both tests must be negative.
    3. continue using 2 different methods of birth control including, at least, one barrier method for at least 30 days after the end of the treatment period

Exclusion Criteria:

  • 1. Evidence of viral resistance against lopinavir/ritonavir, and/or FTC or 3TC, and/or other nucleoside analogues based on the genotype resistance test performed at screening, considering resistance according to the panel IAS - USA, version in December, 2009.

    2. The presence of any of the following major mutations: V32I; I47V / A; L76V; V82A/F/T/S or the presence of two or more minor mutations at positions:10,20,24,33,46,50,53,54,63,71,73,84,90 is considered resistance to lopinavir/ritonavir.

    3. The presence of mutation M184V/I and/or K65R is considered resistance to 3TC or FTC. At the discretion of the investigator and based on the resistance test, a treatment based on lopinavir / ritonavir, plus 3TC or FTC and other similar nucleoside / nucleotide active could not be constructed.

    4. Previously documented HIV-2 infection. 5. Use of disallowed concomitant therapy 6. Patient has a current (active) diagnosis of acute hepatitis due to any cause OR chronic Hepatitis C WITH aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >5 x upper limit of normal (ULN) AND/OR is likely to require treatment in the next year.

    7. Active Hepatitis B infection (regardless of stage of infection). 8. Any active clinically significant disease . 9. Subject has a currently active AIDS defining illness (Category C)30 days of screening. Subjects who are on stable maintenance therapy for an opportunistic infection may be enrolled.

    10. Life expectancy < 1 year according to the judgment of the investigator. 11. Screening laboratory analysis shows any of the following abnormal laboratory results:

    a. Hemoglobin < 8.0 g/dL b. Absolute neutrophil count < 750 cells/µL c. Platelet count < 50,000 mm3 d. Creatinine> 1.5 times the normal upper limit. 12. Subject enrolled in other clinical trials . 13. Use of any investigational agents within 30 days prior to screening. 14. Use of immunosuppressive drugs, cytokine inhibitors or other cytokines in the last year.

    15. Active substance use or abuse that the investigator determines may significantly interfere with study procedures 16. Any condition (including but not limited to alcohol and drug use) which in the opinion of the investigator, could compromise the subject's safety or adherence to the protocol.

    17. Subject is pregnant or breast-feeding.

  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: NCT01237444

Locations
Argentina
Fundacion Huesped
Ciudad de Buenos Aires, Argentina, C1202ABB
Sponsors and Collaborators
Pedro Cahn
Abbott
Investigators
Principal Investigator: Pedro Cahn, MD, PhD FUNDACION HUESPED
  More Information

Additional Information:
No publications provided

Responsible Party: Pedro Cahn, MD, The Huesped Foundation
ClinicalTrials.gov Identifier: NCT01237444     History of Changes
Other Study ID Numbers: FH-10 GARDEL study
Study First Received: November 8, 2010
Last Updated: June 8, 2012
Health Authority: Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health

Keywords provided by The Huesped Foundation:
Lopinavir/ritonavir plus 3TC as a dual therapy regimen.

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamivudine
Ritonavir
Lopinavir
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
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014