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Nucleosides And Darunavir/Dolutegravir In Africa (NADIA)

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ClinicalTrials.gov Identifier: NCT03988452
Recruitment Status : Not yet recruiting
First Posted : June 17, 2019
Last Update Posted : June 17, 2019
Sponsor:
Collaborator:
Infectious Diseases Institute, Uganda
Information provided by (Responsible Party):
Makerere University

Brief Summary:

This trial evaluates options for second-line antiretroviral therapy in patients failing on a non-nucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF)-based first-line regimen in the setting of the public health approach in sub-Saharan Africa (with assumed substantial nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance). The trial tests two hypotheses. Firstly that a regimen of dolutegravir (DTG) with two NRTIs is non-inferior to a regimen of ritonavir-boosted darunavir (DRV/r) with two NRTIs. Secondly that continuing an NRTI regimen of TDF and lamivudine (3TC) is non-inferior to switching to zidovudine (ZDV) and 3TC.

The trial is a parallel group, open-label, multi-centre, factorial (2X2) randomised, controlled trial. Patients will be randomised to either DTG or DRV/r with a second randomisation to ZDV and 3TC or TDF and 3TC. Treatment efficacy will be monitored by testing viral load (VL). Analyses will compare DRV/r with DTG; and ZDV/3TC with TDF/3TC by intention to treat analysis on the primary outcome parameter of plasma VL below 400 copies/ml at 48 weeks. Trial follow-up will continue to 96 weeks.


Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: Darunavir Drug: Ritonavir Drug: Dolutegravir Drug: Zidovudine Drug: Tenofovir Drug: Lamivudine Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nucleosides And Darunavir/Dolutegravir In Africa (NADIA): a Randomised Controlled Trial of Darunavir Versus Dolutegravir and Tenofovir Versus Zidovudine in Second-line Antiretroviral Therapy Regimens for the Public Health Approach in Sub-Saharan Africa
Estimated Study Start Date : June 20, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Darunavir/r Zidovudine Lamivudine
Darunavir 800mg once daily Ritonavir 100mg once daily Zidovudine 300mg twice daily Lamivudine 150mg twice daily Combination given for 96 weeks
Drug: Darunavir
Antiretroviral therapy

Drug: Ritonavir
Antiretroviral therapy

Drug: Zidovudine
Antiretroviral therapy

Drug: Lamivudine
Antiretroviral therapy

Experimental: Darunavir/r Tenofovir Lamivudine
Darunavir 800mg once daily Ritonavir 100mg once daily Tenofovir 300mg once daily Lamivudine 300mg once daily Combination given for 96 weeks
Drug: Darunavir
Antiretroviral therapy

Drug: Ritonavir
Antiretroviral therapy

Drug: Tenofovir
Antiretroviral therapy

Drug: Lamivudine
Antiretroviral therapy

Experimental: Dolutegravir Zidovudine Lamivudine
Dolutegravir 50mg once daily Zidovudine 300mg twice daily Lamivudine 150mg twice daily Combination given for 96 weeks
Drug: Dolutegravir
Antiretroviral therapy

Drug: Zidovudine
Antiretroviral therapy

Drug: Lamivudine
Antiretroviral therapy

Experimental: Dolutegravir Tenofovir Lamivudine
Dolutegravir 50mg once daily Tenofovir 300mg once daily Lamivudine 300mg once daily Combination given for 96 weeks
Drug: Dolutegravir
Antiretroviral therapy

Drug: Tenofovir
Antiretroviral therapy

Drug: Lamivudine
Antiretroviral therapy




Primary Outcome Measures :
  1. Plasma viral load < 400 copies/ml at 48 weeks [ Time Frame: 48 weeks ]

Secondary Outcome Measures :
  1. Plasma viral load < 1000 copies/ml [ Time Frame: 48 and 96 weeks ]
  2. Plasma viral load < 400 copies/ml at 96 weeks [ Time Frame: 96 weeks ]
  3. Plasma viral load < 50 copies/ml [ Time Frame: 48 and 96 weeks ]
  4. Plasma viral load rebound (≥ 1000 copies/ml, confirmed) [ Time Frame: 48 and 96 weeks ]
  5. Plasma viral load rebound (≥ 400 copies/ml, confirmed) [ Time Frame: 48 and 96 weeks ]
  6. Plasma viral load rebound (≥ 50 copies/ml, confirmed) [ Time Frame: 48 and 96 weeks ]
  7. Viral load rebound (≥ 1000 copies/ml, confirmed) with ≥ 1 major resistance mutation (IAS list) to DRV or DTG [ Time Frame: 48 and 96 weeks ]
  8. Viral load rebound (≥ 1000 copies/ml, confirmed) with intermediate or high-level resistance (Stanford algorithm) to DRV or DTG [ Time Frame: 48 and 96 weeks ]
  9. Viral load rebound (≥ 1000 copies/ml, confirmed) with intermediate or high-level resistance (Stanford algorithm) to both zidovudine and tenofovir [ Time Frame: 48 and 96 weeks ]
  10. CD4+ cell count change from baseline [ Time Frame: 48 and 96 weeks ]
  11. Incident (new or recurrent) WHO stage 4 event [ Time Frame: 48 and 96 weeks ]
  12. Incident serious non-AIDS event [ Time Frame: 48 and 96 weeks ]
  13. Death [ Time Frame: 48 and 96 weeks ]
  14. Time to new or recurrent WHO Stage 4 event, serious non-AIDS event, or death [ Time Frame: 96 weeks ]
  15. Grade 3 or 4 clinical adverse events [ Time Frame: 48 and 96 weeks ]
  16. Grade 3 or 4 clinical adverse events (possibly, probably or definitely related to ART) [ Time Frame: 48 and 96 weeks ]
  17. Serious Adverse Events [ Time Frame: 48 and 96 weeks ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, age 12 years and above
  2. Body weight at least 40kg
  3. Taking a tenofovir plus lamivudine/emtricitabine plus NNRTI-based regimen continuously for a total period of at least 6 months
  4. Good adherence to ART, defined as missing medication on no more than 3 days in the one month prior to screening. [Patients who do not have good adherence should be given adherence counselling and re-assessed after an interval of not less than 4 weeks].
  5. HIV treatment failure defined by virological criteria (modified from WHO 2016 criteria); Viral load ≥ 1000 copies/ml at screening AND EITHER Viral load ≥ 1000 copies/ml on the previous test, taken after at least 6 months on ART, and at no more than 6 months prior to screening and at no less than 4 weeks prior to screening, with adherence counselling given after the previous test OR Viral load ≥ 1000 copies/ml on a confirmatory test taken no less than 4 weeks after screening with adherence counselling given after the screening test
  6. If a woman of childbearing potential, must be willing to use effective contraception. [Childbearing potential is defined as being not premenarchal; not post-menopausal (> 12 months of spontaneous amenorrhea and ≥45 years of age); and not permanently sterilised].
  7. Willing and able to provide written informed consent
  8. Able to attend regular study follow-up visits

Exclusion Criteria:

  1. Prior use of protease inhibitor or integrase inhibitor therapy
  2. Requirement for concomitant medication with known major interactions with study drugs for which drug substitutions or dose alterations are not available or acceptable (if the patient requires rifamycin-based TB treatment, rifabutin must be available at the site).
  3. Women who are currently pregnant or breastfeeding.
  4. Severe hepatic impairment (with ascites and/or encephalopathy)
  5. ALT > 5 times upper limit of normal
  6. Estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73m2 at screening calculated using the CKD-EPI equation
  7. Current participation in another clinical trial or research protocol (may be permitted in some circumstances; but must first be discussed with the NADIA Chief Investigator)
  8. Life expectancy of less than one month in the opinion of the treating physician

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): NCT03988452


Contacts
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Contact: Nicholas Paton, MD +65 6772 4380 nick_paton@nuhs.edu.sg
Contact: Anchilla Banegura, MPH +256 312 307 000 ext 219 abanegura@idi.co.ug

Sponsors and Collaborators
Makerere University
Infectious Diseases Institute, Uganda
Investigators
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Study Director: Nicholas Paton, MD National University, Singapore

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Responsible Party: Makerere University
ClinicalTrials.gov Identifier: NCT03988452     History of Changes
Other Study ID Numbers: JC3218
First Posted: June 17, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Ritonavir
Darunavir
Tenofovir
Lamivudine
Zidovudine
Dolutegravir
Lamivudine, zidovudine drug combination
Anti-Retroviral Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors