A Multicentre Trial of Second-line Antiretroviral Treatment Strategies in African Adults Using Atazanavir or Lopinavir/Ritonavir (ALISA)

This study has been withdrawn prior to enrollment.
(drug procurement issues)
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Ludwig-Maximilians - University of Munich
Institute of Tropical Medicine, Belgium
Institut de Recherche pour le Developpement, France
Swiss National Science Foundation
University of Limpopo
NIMR-Mbeya Medical Research Program (MMRP)/ Mbeya Referral Hospital, Tanzania
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01255371
First received: November 29, 2010
Last updated: November 7, 2012
Last verified: November 2012

November 29, 2010
November 7, 2012
March 2012
May 2013   (final data collection date for primary outcome measure)
Virological response [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients with plasma HIV RNA < 50 copies/mL
Same as current
Complete list of historical versions of study NCT01255371 on ClinicalTrials.gov Archive Site
  • Virological response [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
    Proportion of patients with plasma HIV RNA < 400 copies/mL
  • Viral resistance [ Time Frame: 12, 24 and 48 weeks ] [ Designated as safety issue: No ]
    Incidence of resistance mutations after treatment failure (HIV RNA < 1000 copies/mL)
  • Clinical course of HIV infection [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: Yes ]
    Mortality, occurence of clinical events stage 3 or 4 (WHO classification), immune reconstitution sundrome, non-AIDS clinical events including bacterial infections
  • Tolerance assessment [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
    Proportion of adverse events related to antiretroviral treatment, proportion of treatement discontinuations due to antiretroviral side effect, variation of biological parameters and metabolic markers between second line antiretroviral initiation and 24/48 weeks.
  • Adherence assessment [ Time Frame: At each protocol visit : week 2, 4, 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
    Measurement of pills consumption at each visit, face-to-face questionnaire with the pharmacist
  • Hepatitis B evaluation [ Time Frame: At entry ] [ Designated as safety issue: No ]
    Prevalence of HBs AG, HBe Ag, HBV viremia, and HBV asociated drug resistance mutations at baseline
  • Immunologic response [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
    Variation of circulating total and CD4+ lymphocyte count between second line treatment initiation and 24 weeks/48 weeks
Same as current
Not Provided
Not Provided
 
A Multicentre Trial of Second-line Antiretroviral Treatment Strategies in African Adults Using Atazanavir or Lopinavir/Ritonavir
A Multicenter Phase III Trial of Second-line Antiretroviral Treatment Strategies in African Adults (Tanzania Ans South Africa) Using Atazanavir or Lopinavir/Ritonavir

In the well recognized context of HIV infection chronicity, it is now crucial to identify and evaluate effective, well tolerated and affordable second line regimen in resources limited countries where patients often change treatment after a long period of viral replication while on first line regimen.

This multicentre international, randomized, non-blinded phase III trial aim to demonstrate the non-inferiority of a generic lamivudine-tenofovir-atazanavir/ritonavir regimen (daily intake) as compared to a standard emtricitabine-tenofovir-lopinavir/ritonavir (twice daily intake)regimen for second line HIV-1 treatment. by stratifying on the viral load level (between 1000 and 5000 copies/mL versus > 5000 copies/mL) at inclusion, this trial will also allow to evaluate the optimum moment for instituting the second-line treatment.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • Drug: Lopinavir
    Evaluation of second line antiretroviral regimen including boosted lopinavir
  • Drug: Atazanavir
    Evaluation of second line antiretroviral regimen including boosted atazanavir
  • Active Comparator: Arm A : Lopinavir

    Emtricitabine/tenofovir :

    • TDF300mg.FTC200mg (Fixed Dose Combination)
    • 1 tablet per day

    Lopinavir/ritonavir :

    • LPV200mg/RTV50mg
    • 2 tablets twice a day
    Intervention: Drug: Lopinavir
  • Experimental: Arm B : Atazanavir

    Lamivudine/tenofovir :

    • 3TC300mg/TDF300mg (Fixed Dose Combination)
    • 1 tablet per day

    Atazanavir/ritonavir :

    • ATV300mg/RTV100mg
    • 2 tablets once a day
    Intervention: Drug: Atazanavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
December 2014
May 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • age 18 and above
  • out patient
  • documented HIV-1 infection
  • first line treatment failure:

    • after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors
    • two measurements of plasma HIV RNA levels > 1000 copies/mL after at least 6 months of uninterrupted treatment or without any major modification
  • satisfactory compliance (>80%) to 1st line antiretroviral treatment
  • signed informed consent
  • agreement for contraception for women of childbearing age

Exclusion Criteria:

  • HIV-2 infection or HIV-1/HIV-2 coinfection
  • uncontrolled, ongoing opportunistic infection or of any severe or progressive disease including active TB
  • first line antiretroviral treatment with a protease inhibitor or tenofovir
  • ongoing treatment with rifampicin
  • severe hepatic insufficiency (PT < 50%)
  • ALT < 3 times the upper limit of normal
  • creatinine clearance calculated by Cockcroft's formula < 50 mL/min
  • Hb <=8 g/dL; platelets < 50,000 cells/mm3; neutrophils < 500 cells/mm3
  • pregnancy and lactation
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
South Africa,   Tanzania
 
NCT01255371
ANRS 12221 ALISA, IP.07.33011.004
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
  • European and Developing Countries Clinical Trials Partnership (EDCTP)
  • Ludwig-Maximilians - University of Munich
  • Institute of Tropical Medicine, Belgium
  • Institut de Recherche pour le Developpement, France
  • Swiss National Science Foundation
  • University of Limpopo
  • NIMR-Mbeya Medical Research Program (MMRP)/ Mbeya Referral Hospital, Tanzania
Principal Investigator: Eric Delaporte Institut de Recherche pour le Developpement, France
Principal Investigator: Issakwisa Mwakyula NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital, Tanzania
Principal Investigator: Mzileni O Mogiyana University of Limpopo
Principal Investigator: Alexandra Calmy University of Geneva, Switzerland
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP