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Human Immunodeficiency VirusPhase 3NADIANCT03988452

Nucleosides And Darunavir/Dolutegravir In Africa

A Phase 3 study testing Darunavir, Ritonavir and Dolutegravir in people with Human Immunodeficiency Virus, run by Makerere University at 1 site in Uganda.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Human Immunodeficiency Virus
What is being tested?
Darunavir, Ritonavir and Dolutegravir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
465 participants
Where
1 siteUganda
Study dates
30 Jul 2019to 30 Sep 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or female, age 12 years and above
  • Body weight at least 40kg
  • Taking a tenofovir plus lamivudine/emtricitabine plus NNRTI-based regimen continuously for a total period of at least 6 months
  • 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].
  • 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
  • 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].
  • Willing and able to provide written informed consent
  • Able to attend regular study follow-up visits

Who cannot join

  • Prior use of protease inhibitor or integrase inhibitor therapy
  • 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).
  • Women who are currently pregnant or breastfeeding.
  • Severe hepatic impairment (with ascites and/or encephalopathy)
  • ALT > 5 times upper limit of normal
  • Estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73m2 at screening calculated using the CKD-EPI equation
  • 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)
  • Life expectancy of less than one month in the opinion of the treating physician

Trial locations and contacts

1 site in 1 country.

Uganda1 site

  • Infectious Diseases Institute

    Kampala

Other trials in Uganda

About this study

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

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.

Being tested
Darunavir, Ritonavir, Dolutegravir, Zidovudine, Tenofovir
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarunavirDrug

    Antiretroviral therapy

  • RitonavirDrug

    Antiretroviral therapy

  • DolutegravirDrug

    Antiretroviral therapy

  • ZidovudineDrug

    Antiretroviral therapy

  • TenofovirDrug

    Antiretroviral therapy

  • LamivudineDrug

    Antiretroviral therapy

Study groups in NCT03988452
Study groupRoleWhat they receive
Darunavir/r Zidovudine LamivudineActive comparatorDarunavir 800mg once daily Ritonavir 100mg once daily Zidovudine 300mg twice daily Lamivudine 150mg twice daily Combination given for 96 weeks
Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Zidovudine; Drug: Lamivudine
Darunavir/r Tenofovir LamivudineExperimentalDarunavir 800mg once daily Ritonavir 100mg once daily Tenofovir 300mg once daily Lamivudine 300mg once daily Combination given for 96 weeks
Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Tenofovir; Drug: Lamivudine
Dolutegravir Zidovudine LamivudineExperimentalDolutegravir 50mg once daily Zidovudine 300mg twice daily Lamivudine 150mg twice daily Combination given for 96 weeks
Receives: Drug: Dolutegravir; Drug: Zidovudine; Drug: Lamivudine
Dolutegravir Tenofovir LamivudineExperimentalDolutegravir 50mg once daily Tenofovir 300mg once daily Lamivudine 300mg once daily Combination given for 96 weeks
Receives: Drug: Dolutegravir; Drug: Tenofovir; Drug: Lamivudine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma viral load < 400 copies/ml at 48 weeks

    Measured: 48 weeks

Secondary outcomes (17)

  1. Plasma viral load < 1000 copies/ml

    Measured: 48 and 96 weeks

  2. Plasma viral load < 400 copies/ml at 96 weeks

    Measured: 96 weeks

  3. Plasma viral load < 50 copies/ml

    Measured: 48 and 96 weeks

  4. Plasma viral load rebound (≥ 1000 copies/ml, confirmed)

    Measured: 48 and 96 weeks

  5. Plasma viral load rebound (≥ 400 copies/ml, confirmed)

    Measured: 48 and 96 weeks

  6. Plasma viral load rebound (≥ 50 copies/ml, confirmed)

    Measured: 48 and 96 weeks

  7. Viral load rebound (≥ 1000 copies/ml, confirmed) with ≥ 1 major resistance mutation (IAS list) to DRV or DTG

    Measured: 48 and 96 weeks

  8. Viral load rebound (≥ 1000 copies/ml, confirmed) with intermediate or high-level resistance (Stanford algorithm) to DRV or DTG

    Measured: 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

    Measured: 48 and 96 weeks

  10. CD4+ cell count change from baseline

    Measured: 48 and 96 weeks

  11. Incident (new or recurrent) WHO stage 4 event

    Measured: 48 and 96 weeks

  12. Incident serious non-AIDS event

    Measured: 48 and 96 weeks

  13. Death

    Measured: 48 and 96 weeks

  14. Time to new or recurrent WHO Stage 4 event, serious non-AIDS event, or death

    Measured: 96 weeks

  15. Grade 3 or 4 clinical adverse events

    Measured: 48 and 96 weeks

  16. Grade 3 or 4 clinical adverse events (possibly, probably or definitely related to ART)

    Measured: 48 and 96 weeks

  17. Serious Adverse Events

    Measured: 48 and 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2019
  2. Study start30 Jul 2019
  3. Primary completion30 Sep 2020 (estimated)
  4. Study completion30 Sep 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
465 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03988452
Sponsor's protocol ID
JC3218
Acronym
NADIA
Status last verified
Jul 2020
First submitted
13 Jun 2019
Last updated
30 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, Asienzo J, Kaimal A, Mirembe G, Lugemwa A, Ategeka G, Borok M, Mugerwa H, Siika A, Odongpiny ELA, Castelnuovo B, Kiragga A, Kambugu A; NADIA Trial Team. Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. Lancet HIV. 2022 Jun;9(6):e381-e393. doi: 10.1016/S2352-3018(22)00092-3. Epub 2022 Apr 20.

    PubMed 35460601

  • Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, Kaimal A, Mirembe G, Tukamushabe P, Ategeka G, Hakim J, Mugerwa H, Siika A, Asienzo J, Castelnuovo B, Kiragga A, Kambugu A; NADIA Trial Team. Dolutegravir or Darunavir in Combination with Zidovudine or Tenofovir to Treat HIV. N Engl J Med. 2021 Jul 22;385(4):330-341. doi: 10.1056/NEJMoa2101609.

    PubMed 34289276

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Darunavir, Ritonavir and Dolutegravir in people with Human Immunodeficiency Virus, run by Makerere University at 1 site in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma viral load < 400 copies/ml at 48 weeks (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03988452, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2020.

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