HIV Infections Clinical Trial
— RADIANT-TBOfficial title:
Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis: a Phase 2 Non-comparative Randomised Controlled Trial
Verified date | November 2022 |
Source | University of Cape Town |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The investigators propose to conduct a phase 2 randomised (1:1) double-blind placebo-controlled trial of the dolutegravir-lamivudine-tenofovir fixed dose combination tablet daily with an additional 50 mg dose of dolutegravir/matching placebo taken 12 hours later in ART-naïve or fisrt-line interrupted HIV-infected patients on rifampicin-based anti-tuberculosis therapy. The hypothesis is that virologic outcomes with standard dose dolutegravir-based ART will be acceptable in patients on rifampicin-based anti-tuberculosis therapy.
Status | Completed |
Enrollment | 108 |
Est. completion date | June 28, 2022 |
Est. primary completion date | January 20, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 110 Years |
Eligibility | Inclusion Criteria: - HIV-1 infection as documented by screening plasma HIV-1 RNA >1000 c/mL - ART-naïve (short-term antiretroviral use for prevention of mother-to-child transmission will be allowed) or - ART treatment interrupters on ART <6 months prior to interruption or virologically suppressed (<50 copies/mL or LDL) <6 months prior to interruption - On rifampicin-based therapy for tuberculosis for <3 months - CD4 counts >100 cells/µL - Women of child-bearing potential willing to use adequate contraception (defined as either an intrauterine contraceptive device or hormonal contraception as per national guidelines) Exclusion Criteria: - Pregnant/breastfeeding - Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease (MDRD) study) - Alanine aminotransferase >3 times upper limit of normal (ULN) - Allergy or intolerance to one of the drugs in regimen - Concomitant medication known to significantly reduce or increase dolutegravir exposure (except rifampicin) - Active psychiatric disease or substance abuse - On treatment for active AIDS-defining condition other than tuberculosis (participants on maintenance therapy may be enrolled) - Malignancy - Any other clinical condition that in the opinion of an investigator puts the patient at increased risk of participating in the study. |
Country | Name | City | State |
---|---|---|---|
South Africa | Khayelitsha Site B/Ubuntu Clinic | Cape Town | Western Cape |
Lead Sponsor | Collaborator |
---|---|
University of Cape Town | Medecins Sans Frontieres, Netherlands, Wellcome Trust |
South Africa,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Virological Suppression at 24 Weeks | Proportion with HIV viral load <50 copies/mL at 24 weeks analysed by modified intention to treat (ITT), which includes all participants who received at least one dose of dolutegravir, and according to the FDA snapshot algorithm. | 24 weeks | |
Secondary | Virological Suppression at 12 Weeks (Modified ITT) | Proportion with HIV viral load <50 copies/mL at 12 weeks analyzed modified ITT. | 12 weeks | |
Secondary | Virological Suppression at 24 Weeks (Per Protocol) | Proportion with HIV viral load <50 copies/mL at 24 weeks analyzed per protocol. | 24 weeks | |
Secondary | Virological Suppression at 48 Weeks (Modified ITT) | Proportion with HIV viral load <50 copies/mL at 48 weeks analyzed modified ITT. | 48 weeks | |
Secondary | Virological Suppression at 48 Weeks (Per Protocol) | Proportion with HIV viral load <50 copies/mL at 48 weeks analyzed per protocol. | 48 weeks | |
Secondary | CD4 Change at 24 and 48 Weeks | Change in CD4 count from screening at week 24 and week 48. | 24 and 48 weeks | |
Secondary | Dolutegravir Trough Concentrations | Proportion with dolutegravir trough concentrations above the PA IC90 at weeks 4, 8, 12, 24, and 48. | 4, 8, 12, 24, and 48 weeks | |
Secondary | Grade 3 or 4 Adverse Events | Grade 3 or 4 drug-related adverse events will be accessed throughout the trial. | 48 weeks | |
Secondary | Change in Sleep Assessment From Baseline | Insomnia severity scale - measures sleep patterns and how this influences daily functioning and quality of life (assessed at weeks 4, 8, 12, 16, 20, 24, and 48). Please rate the current (i.e. last 2 weeks) severity of your insomnia problem(s): None, Mild, Moderate, Severe, Very Severe How satisfied/dissatisfied are you with your current sleep pattern? 0 - 5 (Very Satisfied - Very Dissatisfied) To what extent do you consider your sleep problem to interfere with your daily functioning? 0 - 4 (Not interfering at all, A little, Somewhat, Much, Interfering very much) How noticeable to others do you think your sleeping problem is in terms of impairing the quality of your life? 0 - 4 (Not noticeable at all, Barely, Somewhat, Much, Very much noticeable) How worried/distressed are you about your current sleep problem? 0 - 4 (Not noticeable at all, A little, Somewhat, Much, Very much) |
4, 8, 12, 16, 20, 24, and 48 weeks | |
Secondary | Change in Mental Health Assessment From Baseline | Mental health will be assessed by a questionnaire given at baseline, 12 weeks, 24 weeks, and 48 weeks. The questionnaire is standardized and has been based on the mini international neuropsychiatric interview (version 7.0.0). All questions in the questionnaire require a yes/no answer. | 12, 24, and 48 weeks | |
Secondary | Serious Adverse Events | Document any serious adverse events that occur throughout the trial. | 48 weeks | |
Secondary | Adverse Events Requiring Discontinuation of an ART Drug | Any adverse event that requires discontinuation of any drug in the ART regimen throughout the trial. | 48 weeks | |
Secondary | Antiretroviral Resistance Mutations Testing by Genotypic Resistance Assay in Participants With Virologic Failure | If a viral load is >1000 copies/mL at week 24 or at week 48, or if the viral load was suppressed and then rebounded to >1000 copies/mL, a sample will be taken for resistance testing. Antiretroviral resistance mutations in participants with virologic failure will be assessed by genotypic resistance assay and compared to stored plasma at baseline to distinguish emergent from pre-treatment resistance. | 24 and 48 weeks | |
Secondary | Primary Outcome Differences Among ART-naïve Versus First-line Interruption Status | The primary outcome measure (proportion with HIV viral load <50 copies/mL at 24 weeks analysed by modified intention to treat (ITT), which includes all participants who received at least one dose of dolutegravir, and according to the FDA snapshot algorithm) will be stratified by ART-naïve versus first-line interruption status. | 24 weeks | |
Secondary | Secondary Outcome Differences Among ART-naïve Versus First-line Interruption Status by Modified ITT Analysis | Virological suppression at 12 and 48 weeks by modified ITT analysis will be stratified by ART-naïve versus first-line interruption status. | 12 and 48 weeks | |
Secondary | Secondary Outcome Differences Among ART-naïve Versus First-line Interruption Status by Per Protocol Analysis | Virological suppression at 12, 24, and 48 weeks by per protocol analysis will be stratified by ART-naïve versus first-line interruption status. | 12, 24, and 48 weeks |
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