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Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé) (2LADY)

This study has been completed.
Sponsor:
Collaborators:
Gilead Sciences
Janssen Pharmaceutica
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:
NCT00928187
First received: June 23, 2009
Last updated: September 21, 2016
Last verified: September 2016

June 23, 2009
September 21, 2016
November 2009
September 2013   (final data collection date for primary outcome measure)
Number of Patients With Plasma HIV RNA < 50 Copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
proportion of patients with plasma HIV RNA < 50 copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00928187 on ClinicalTrials.gov Archive Site
  • Number of Patients With WHO Stage 3 and 4 HIV Related Events [ Time Frame: between baseline and 48 weeks ] [ Designated as safety issue: Yes ]
    patients having a diagnosis of HIV related event classified as stage 3 or 4
  • Patients With Plasma HIV RNA < 200 Copies/ml [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    number of patients with plasma HIV RNA below 200 copies/ml
  • Gain in CD4 Cells Between Baseline and W48 [ Time Frame: between baseline and 48 weeks ] [ Designated as safety issue: No ]
    median gain in circulating CD4 cells between baseline and W48
  • Number of Patients Discontinuing Study Treatment [ Time Frame: between baseline and W48 ] [ Designated as safety issue: Yes ]
    number of patients discounting treatment because of adverse events
  • Tolerance: Gastrointestinal Complains [ Time Frame: between baseline and 48 weeks ] [ Designated as safety issue: Yes ]
    Gastrointestinal complaints (grade 1 to 4) between baseline and W48.
  • Tolerance: Neuropathies (Grade 1 to 4) [ Time Frame: between baseline and W48 ] [ Designated as safety issue: Yes ]
    any symptom of peripheral neuropathy
  • Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate) [ Time Frame: between baseline and W48 ] [ Designated as safety issue: Yes ]
    evaluation of estimated glomerular filtration rate and number of participant with a decrease equal or superior to 25% of the baseline value
  • Adherence [ Time Frame: between baseline and W48 ] [ Designated as safety issue: No ]
    number of patients in different categories of adherence as measured by questionnaire
  • Number of Patients With Resistance Mutations [ Time Frame: between W12 and W48 ] [ Designated as safety issue: No ]
    number of patients with resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml)
  • clinical outcome (AIDS events, non-AIDS events, death, undesirable effects) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • proportion of patients with plasma HIV RNA < 200 and 50 copies/ml [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • proportion of patients with plasma HIV RNA < 200 copies/ml [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • variation of circulating CD4+ lymphocyte count [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • treatment discontinuation [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • tolerance, particularly the occurrence of hypersensitivity syndromes, renal impairment, and changes in lipids profile, gastrointestinal complains and lipodystrophy [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • changes in anthropometric measures [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • adherence (measured by pill count and questionnaire) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • frequency of resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé)
Multicentric, Non-inferiority, Randomized, Non-blinded Phase 3 Trial Comparing Virological Response at 48 Weeks of 3 Antiretroviral Treatment Regimens in HIV-1-infected Patients With Treatment Failure After 1st Line Antiretroviral Therapy (Cameroon, Burkina Faso, Senegal)

Since the first line antiretroviral (ARV) treatment is now largely accessible in the Sub-Saharian Africa countries, documentation of virological failure, drug resistance patterns and second line treatment evaluation are still to be consolidated in settings where viral load monitoring is not available and non-B HIV subtype is predominant.

This trial aims at evaluating the efficacy and tolerance of 3 different second line treatment strategies: two recommended by WHO combine two non-nucleoside reverse transcriptase inhibitor associated with a ritonavir boosted protease inhibitor (emtricitabine-tenofovir-lopinavir/ritonavir and abacavir-didanosine-lopinavir/ritonavir); the third strategy combines emtricitabine-tenofovir-darunavir/ritonavir and is not yet evaluated in Sub-Saharian Africa. Darunavir has a potentially superior antiviral efficacy, a better tolerance and its single daily administration may facilitate treatment adherence.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV
  • HIV Infections
  • Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
    Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets in the morning and 2 tablets in the evening
  • Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
    Didanosine 1 entero-coated capsule/day in fasting conditions (dosage 250 mg if weight < 60 kg, 400 mg if weight > 60 kg) + abacavir 300 mg 1 tablet in the morning and in the evening + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets morning and evening
  • Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
    Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + darunavir 400 mg 2 tablets + ritonavir 100 mg 1 capsule, in a single dose with food
  • Active Comparator: Arm A
    emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
    Intervention: Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
  • Active Comparator: Arm B
    abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
    Intervention: Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
  • Active Comparator: Arm C
    emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
    Intervention: Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
454
December 2015
September 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient over the age of 18 years at pre-inclusion and monitored under outpatient conditions
  • Documented HIV-1 infection regardless of clinical stage and CD4 lymphocyte count
  • Patient with treatment failure after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, failure being defined as 2 measurements (at 1 month interval) of plasma HIV RNA levels > 1000 copies/ml after at least 6 months of uninterrupted treatment
  • Adherence (> 80%) to first- line antiretroviral treatment (questionnaire) at pre inclusion
  • Patient agrees not to take any concomitant medication during the trial without informing the investigator
  • Informed consent signed no later than D-15
  • For women in childbearing age: negative pregnancy test at inclusion, with no plan of pregnancy in the coming 12 months and agreeing to use mechanical contraception (with or without hormonal contraception) during the study

Exclusion Criteria:

  • Infection with HIV-2 or HIV-1 groups O or N or HIV1+2
  • Deficiency of the patient, making it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
  • Participation in any other clinical trial
  • Presence of an uncontrolled, ongoing opportunistic infection or of any severe or progressive disease
  • First-line treatment with a protease inhibitor, abacavir, tenofovir or ddI
  • Ongoing treatment with rifampicin
  • Severe hepatic insufficiency (TP < 50%)
  • ALAT > 3 x ULN
  • Creatinine clearance calculated by Cockcroft formula < 50 ml/min
  • Hb ≤ 8 g/dl
  • Platelets < 50,000 cells/mm3
  • Neutrophiles < 500 cells/ mm3
  • Use of drugs prohibited in the context of this trial (drugs contraindicated by the SCP of the trial drugs) - in the event of tuberculosis or malaria during the trial, a list of authorized medicines and, if necessary, a dose adjustment of the antiretroviral medication will be provided
  • Pregnancy or lactation
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Burkina Faso,   Cameroon,   Senegal
 
NCT00928187
ANRS12169 2LADY
Yes
Not Provided
Not Provided
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)
  • Gilead Sciences
  • Janssen Pharmaceutica
Principal Investigator: Sinata Koulla Shiro, PhD Infectious diseases department, Central Hospital, Yaounde, Cameroon
Principal Investigator: Papa Salif Sow, PhD Infectious Diseases Department, Fann Hospital, Dakar, Senegal
Principal Investigator: Adrien Sawadogo, MD Day Hospital, CHU Sanou Souro, Bobo Dioulasso, Burkina Faso
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
September 2016

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