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Completed

NCT Number: NCT02777229

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

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, 96 and 192 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, 96 and 192 weeks between the two arms including the proportion of patients with viral load <50 copies/mL and incidence of severe adverse events.

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Key information

Conditions

HIV-1 Infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Cité verte Hospital, Yaoundé, Cameroon

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Dolutegravir 50 mg

Drug

1 tablet once a day

Other names: DTG

Tenofovir disoproxil fumarate 300 mg / lamivudine 300 mg

Drug

Fixed dose combination, 1 tablet once a day

Other names: TDF / 3TC

Efavirenz 400 mg

Drug

1 tablets once a day

Other names: EFV400

Primary outcomes

  1. Proportion of patients with Viral Load (VL) <50 cp/mL

    Time frame: week 48

    Proportion of patients with Viral Load (VL) <50 cp/mL at week 48 (FDA snapshot algorithm)

Secondary outcomes

  1. Proportion of patients with Viral Load (VL) <50 cp/mL

    Time frame: week 96

    Proportion of patients with Viral Load (VL) <50 cp/mL at week 96 (FDA snapshot algorithm)

  2. Proportion of patients with Viral Load (VL) <50 cp/mL

    Time frame: week 24

    Proportion of patients with VL< 50 cp/mL at week 24 (FDA snapshot algorithm)

  3. Proportion of patients with Viral Load (VL) < 200 cp/mL

    Time frame: week 24, week 48, week 96, week 144, week 192

    Proportion of patients with VL< 200 cp/mL (FDA snapshot algorithm)

  4. Time to virologic failure

    Time frame: week 48, week 96, week 144, week 192

    Time to virologic failure

  5. Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in Cluster of differentiation 4 (CD4)-cell count from baseline to endpoints week-48, -96, -144, -192

  6. Time to death or to disease progression

    Time frame: week 48, week 96, week 144, week 192

    Time to death or to disease progression

  7. Time to first toxicity failure

    Time frame: week 48, week 96, week 144, week 192

    Time to first toxicity failure

  8. Incidence of first grade 3 or 4 clinical adverse event

    Time frame: week 48, week 96, week 144, week 192

    Incidence of first grade 3 or 4 clinical adverse event

  9. Incidence of first grade 3 or 4 laboratory adverse event

    Time frame: week 48, week 96, week 144, week 192

    Incidence of first grade 3 or 4 laboratory adverse event

  10. AE and SAE

    Time frame: week 48, week 96, week 144, week 192

    Incidence of adverse events (AE) and serious adverse event (SAE)

  11. Time to treatment discontinuation

    Time frame: week 48, week 96, week 144, week 192

    Time to treatment discontinuation

  12. Hemoglobine changes from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in hemoglobin Time to virologic failure from baseline to endpoints week-48, -96, -144, -192

  13. Changes in creatinine from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in creatinine from baseline to endpoints week-48, -96, -144, -192

  14. Changes in estimated glomerular filtration rate from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in estimated glomerular filtration rate from baseline to endpoints week-48, -96, -144, -192

  15. Changes in Aspartate Aminotransferase (AST) ffrom baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in Aspartate Aminotransferase (AST) from baseline to endpoints week-48, -96, -144, -192

  16. Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in Alanine Aminotransferase (ALT) from baseline to endpoints week-48, -96, -144, -192

  17. Changes in level of fasting glucose from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in level of fasting glucose from baseline to endpoints week-48, -96, -144, -192

  18. Changes in level of total cholesterol from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in level of total cholesterol from baseline to endpoints week-48, -96, -144, -192

  19. Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in level of triglycerides from baseline to endpoints week-48, -96, -144, -192

  20. Changes in level of HDL from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Changes in level of HDL from baseline to endpoints week-48, -96, -144, -192

  21. Proportion of patients defaulting clinic schedule

    Time frame: week 48, week 96, week 144, week 192

    Proportion of patients defaulting clinic schedule

  22. Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192

    Time frame: week 48, week 96, week 144, week 192

    Mean medication adherence level from baseline to endpoints week-48, -96, -144, -192

  23. Mean change in Depression Anxiety Stress Scale from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Mean change in Depression Anxiety Stress Scale from baseline to endpoints week-48, -96, -144, -192

    • Depression Normal 0-9, Mild 10-13, Moderate 14-20, Severe 21-27, Extremely Severe +28
    • Anxiety Normal 0-7, Mild 8-9, Moderate 10-14, Severe 15-19, Extremely Severe +20
    • Stress Normal 0-14, Mild 15-18, Moderate 19-25, Severe 26-33, Extremely Severe +34

  24. Mean change in Quality of life score assessed by the Short Form health survey from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Mean change in Quality of life score assessed by the Short Form health survey from baseline to endpoints week-48, -96, -144, -192 (Score varies according to the items, in order to test the vigilance of the patient. Reading the results provides a semantic appreciation)

  25. Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192

    Time frame: Baseline, week 48, week 96

    Mean change in EFV-related symptoms questionnaire score from baseline to endpoints week-48, -96, -144, -192

  26. Tobacco status consumtion

    Time frame: week 192

    The status of tobacco smoker / non-smoker will be requested.

  27. HbA1c

    Time frame: week 192

    Levels of glycated hemoglobin

  28. hsPCR

    Time frame: week 192

    Levels of high sensitivity protein C reactive

  29. Lipodistrophia

    Time frame: week 192

    Qualitative and quantitative measurements of soft tissue composition = Lipodistrophia

  30. CIMT

    Time frame: week 192

    Mesures of Carotid Intima-Media Thickness

  31. PWV

    Time frame: week 192

    Mesures of Pulse Wave Velocity

  32. Levels of adiponectin

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Levels of adiponectin

  33. Levels of leptin

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Levels of leptin

  34. Levels of ghrelin

    Time frame: Baseline, week 48, week 96, week 144, week 192

    Levels of ghrelin

Sponsors and collaborators

Lead sponsor

ANRS, Emerging Infectious Diseases

Other Gov

Collaborators

  • Institut de Recherche pour le Developpement
  • UNITAID

Registry information

Official study 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

Acronym: NAMSAL

Important dates

Study start
2016
Primary completion
2018
Study completion
2021
First posted
May 19, 2016
Registry last updated
Aug 31, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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