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Efficacy and Safety of a Dolutegravir-based Regimen for the Initial Management of HIV Infected Adults in Resource-limited Settings (NAMSAL)

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ClinicalTrials.gov Identifier: NCT02777229
Recruitment Status : Active, not recruiting
First Posted : May 19, 2016
Last Update Posted : July 3, 2018
Sponsor:
Collaborator:
Institut de Recherche pour le Developpement
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)

Brief Summary:

Several reports indicate that treatment failure due to HIV resistance or to adverse event-related discontinuation could compromise the effectiveness of scaling-up antiretroviral treatment (ART), especially when lack of access to viral load is a concern. Combined with other nucleoside reverse transcriptase inhibitor, Dolutegravir (DTG) is a very promising alternative to the current first-line non nucleoside reverse transcriptase inhibitor-based regimens.

Initial evaluations of DTG conducted in high income countries showed excellent efficacy and safety and indicated high genetic barrier thus preserving second line treatment. As a consequence, DTG-based regimens have been recently included in the first-line options in the national guidelines for ART of several high-income countries. However, the clinical trials evaluating DTG-based regimens have been conducted in highly controlled conditions, including baseline resistance testing and regular viral load monitoring. Moreover, these trials included a high proportion of men with rare co-morbidities.

There is need to evaluate how a DTG-based regimen will perform in real-world conditions within resources-constrained settings, where viral load monitoring is limited, and where the majority of HIV patients are women with important family planning consideration and NAMSAL trial is a randomized clinical trial which aims to evaluate efficacy and safety over 48 weeks of DTG + tenofovir disoproxil fumarate/lamivudine versus Efavirenz (EFV) + tenofovir disoproxil fumarate/lamivudine in 606 ART-naïve HIV-1-infected adults in Cameroon. A set of efficacy and safety endpoints will be compared over 48 weeks between the two arms including the proportion of patients with viral load <50 copies/mL and incidence of severe adverse events.


Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Dolutegravir 50 mg Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg Drug: Efavirenz 200 mg Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 616 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Open Label Trial to Evaluate Dolutegravir Versus Efavirenz 400 mg, Both Combined With Tenofovir Disoproxil Fumarate + Lamivudine for the Initial Management of HIV Infected Adults in Resource-limited Settings
Actual Study Start Date : July 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018


Arm Intervention/treatment
Experimental: Dolutegravir
Dolutegravir 50 mg Quaque die (QD) + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg Fixed Dose Combination (FDC) QD
Drug: Dolutegravir 50 mg
1 tablet once a day

Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg
Fixed dose combination, 1 tablet once a day

Active Comparator: Efavirenz
Efavirenz 400 mg QD + tenofovir disoproxil fumarate/lamivudine 300 mg/ 300 mg FDC QD
Drug: Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg
Fixed dose combination, 1 tablet once a day

Drug: Efavirenz 200 mg
2 tablets once a day




Primary Outcome Measures :
  1. Proportion of patients with Viral Load (VL) <50 cp/mL at week 48 (FDA snapshot algorithm) [ Time Frame: week 48 ]

Secondary Outcome Measures :
  1. Proportion of patients with VL< 50 cp/mL at week 24 (FDA snapshot algorithm) [ Time Frame: week 24 ]
  2. Proportion of patients with VL< 200 cp/mL at week 48 (FDA snapshot algorithm) [ Time Frame: week 48 ]
  3. Proportion of patients with VL< 200 cp/mL at week 24 (FDA snapshot algorithm) [ Time Frame: week 24 ]
  4. Time to virologic failure [ Time Frame: 48 weeks ]
  5. Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to week 48 [ Time Frame: Baseline and 48 weeks ]
  6. Time to death or to disease progression [ Time Frame: up to 48 weeks ]
  7. Time to first toxicity failure [ Time Frame: up to 48 weeks ]
  8. Incidence of first grade 3 or 4 clinical adverse event [ Time Frame: up to 48 weeks ]
  9. Incidence of first grade 3 or 4 laboratory adverse event [ Time Frame: up to 48 weeks ]
  10. Incidence of adverse events (AE) and serious adverse event (SAE) [ Time Frame: up to 48 weeks ]
  11. Time to treatment discontinuation [ Time Frame: 48 weeks ]
  12. Change from baseline to week 48 in hemoglobin [ Time Frame: Baseline and 48 weeks ]
  13. Change from baseline to week 48 in creatinine [ Time Frame: Baseline and 48 weeks ]
  14. Change from baseline to week 48 in estimated glomerular filtration rate [ Time Frame: Baseline and 48 weeks ]
  15. Change from baseline to week 48 in Aspartate Aminotransferase (AST) [ Time Frame: Baseline and 48 weeks ]
  16. Change from baseline to week 48 in Alanine Aminotransferase (ALT) [ Time Frame: Baseline and 48 weeks ]
  17. Change from baseline to week 48 in level of fasting glucose [ Time Frame: Baseline and 48 weeks ]
  18. Change from baseline to week 48 in level of total cholesterol [ Time Frame: Baseline and 48 weeks ]
  19. Change from baseline to week 48 in level of triglycerides [ Time Frame: Baseline and 48 weeks ]
  20. Change from baseline to week 48 in level of HDL [ Time Frame: Baseline and 48 weeks ]
  21. Proportion of patients defaulting clinic schedule [ Time Frame: 48 weeks ]
  22. Mean adherence level overall [ Time Frame: 48 weeks ]
  23. Mean change in Depression Anxiety Stress Scale [ Time Frame: Baseline and 48 weeks ]
  24. Mean change in Quality of life score assessed by the Short Form health survey [ Time Frame: Baseline and 48 weeks ]
    composite score

  25. Mean change in EFV-related symptoms questionnaire score [ Time Frame: Baseline and 48 weeks ]
    composite score



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected
  • Age ≥ 18 years
  • Abtiretroviral-naïve, including above 7 days of cumulative prior antiretroviral therapy at any time prior to study entry.
  • For women of childbearing potential: acceptance to use effective contraceptive methods
  • Provision of written informed consent

Exclusion Criteria:

  • Infection with HIV-1 group O, N, P
  • Infection or co-infection with HIV-2
  • Absolute neutrophil count (ANC) < 500 cells/mm3
  • Hemoglobin < 7.0 g/dL
  • Platelet count < 50,000 cells/mm3
  • AST and/or ALT > 5 x Upper Limit of Normal (ULN)
  • Calculated creatinine clearance < 50 mL/min
  • Active opportunistic or severe disease not under adequate control
  • For women of childbearing age : Pregnancy/breastfeeding
  • History or presence of allergy and/or contraindications to the trial drugs or their components
  • Severe psychiatric illness
  • Severe hepatic failure Patients co-infected with tuberculosis (TB), receiving a TB treatment and with stable clinical condition will not be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02777229


Locations
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Cameroon
Cité verte Hospital
Yaoundé, Cameroon
Hopital Central
Yaoundé, Cameroon
Military Hospital
Yaoundé, Cameroon
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Institut de Recherche pour le Developpement
Investigators
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Principal Investigator: Eric Delaporte, MD, PhD IRD, INSERM, University Montpellier
Principal Investigator: Charles Kouanfack, MD, PhD Central Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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: NCT02777229     History of Changes
Other Study ID Numbers: ANRS 12313 NAMSAL
First Posted: May 19, 2016    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
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Tenofovir
Lamivudine
Efavirenz
Dolutegravir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
HIV Integrase Inhibitors
Integrase Inhibitors