Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis

NCT03851588 | Completed Phase 2 Results DMC

• 1 other identifier: CIDRI003
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections; Tuberculosis

Keywords

Antiretroviral therapy; Dolutegravir; Rifampicin; Tuberculosis; Drug-drug interaction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Virological Suppression at 12 Weeks (Modified ITT)

  12 weeks

• Virological Suppression at 24 Weeks (Per Protocol)

  24 weeks

• Virological Suppression at 48 Weeks (Modified ITT)

  48 weeks

• Virological Suppression at 48 Weeks (Per Protocol)

  48 weeks

• CD4 Change at 24 Weeks

  24 weeks

Study Arms (2)

Supplementary dose

ACTIVE COMPARATOR

Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later.

Drug: Dolutegravir 50 mg

Placebo dose

PLACEBO COMPARATOR

Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later.

Other: Placebo

Interventions

Placebo OTHER

Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.

Placebo dose

Dolutegravir 50 mg DRUG

Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.

Also known as: Tivicay 50 mg

Supplementary dose

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cape Town: lead
• Wellcome Trust: collaborator
• Medecins Sans Frontieres, Netherlands: collaborator

Study Sites (1)

Khayelitsha Site B/Ubuntu Clinic

Cape Town, Western Cape, 8001, South Africa

Location

Related Publications (2)

• Griesel R, Zhao Y, Simmons B, Omar Z, Wiesner L, Keene CM, Hill AM, Meintjes G, Maartens G. Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB): a phase 2, non-comparative, randomised controlled trial. Lancet HIV. 2023 Jul;10(7):e433-e441. doi: 10.1016/S2352-3018(23)00081-4. Epub 2023 May 22.

  PMID: 37230101 DERIVED

• Griesel R, Hill A, Meintjes G, Maartens G. Standard versus double dose dolutegravir in patients with HIV-associated tuberculosis: a phase 2 non-comparative randomised controlled (RADIANT-TB) trial. Wellcome Open Res. 2021 Jan 11;6:1. doi: 10.12688/wellcomeopenres.16473.1. eCollection 2021.

  PMID: 33954265 DERIVED

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Results Point of Contact

• Title: Prof Gary Maartens
• Organization: University of Cape Town

gary.maartens@uct.ac.za

214066008

Study Officials

• Gary Maartens, MMed

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Division of Clinical Pharmacology

Model Details: Parallel assignment of randomised groups with stratification by ART-naïve versus first-line interrupter status

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 22, 2019
• Study Start: December 19, 2019
• Primary Completion: January 20, 2022
• Study Completion: June 28, 2022
• Last Updated: July 18, 2024
• Results First Posted: September 18, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From the time the final results are published
• Access Criteria: Data will be shared with other organizations or individuals for further research upon a reasonable request to the University of Cape Town PI, provided that certain conditions are met (including but not limited to the ethical standards upheld by HREC that approved the initial study.

Locations

ZA (1)