Efficacy of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients

Shanghai Public Health Clinical Center

Status and phase: Unknown; Phase 3

Conditions: Tuberculosis; HIV Infections

Treatments: Drug: Efavirenz 600mg; Drug: Efavirenz 400mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04513379

EDOSE

Details and patient eligibility

About

TB is the most common cause of death in patients with HIV worldwide. Rifampicin [RIF] is the cornerstone of anti-TB therapy. Current guideline recommend efavirenz (EFV) 600mg per day as the first of choice for HIV/TB co-infection. Co-administration of EFV with RIF decrease the plasma concentration of EFV. Because of better safety profiles, EFV 400mg has replaced the EFV 600mg as the first-line antiretroviral therapy in people living with HIV. However, the efficacy of EFV 400mg when co-administrated with RIF in HIV/TB co-infection is unclear. This study is designed to evaluate the efficacy and safety of EFV 400mg versus EFV 600mg in HIV/TB co-infected patients receiving RIF based anti-TB therapy.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject or the subject's legal representative is willing and able to understand and provide signed and dated written informed consent prior to Screening
• Adult subject (at least 18 years of age)
• Naive to antiretroviral therapy (<=14 days of prior therapy with any antiretroviral drug following a diagnosis of HIV-1 infection)
• CD4+ cell count is >= 50 cells/ cubic millimetre (mm^3) at Screening
• A female subject may be eligible to enter and participate in the study if she: is of non-childbearing potential defined as either postmenopausal (12 months of spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming pregnant or does not want to pregnancy
• New diagnosis of TB (microbiology or molecular methods or clinical diagnosis) and started rifampicin based regimen for less no longer than 8 weeks at screening

Exclusion criteria

• Evidence of RIF resistance of Mycobacterium tuberculosis either by culture or validated nucleic acid amplification test
• Concomitant disorders or conditions for which isoniazid, RIF, pyrazinamide, or ethambutol are contraindicated
• Central nervous system TB
• Women who are pregnant or breastfeeding
• Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification unstable liver disease
• Anticipated need for hepatitis C virus (HCV) therapy during the study period
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class
• Subjects who, in the investigator's judgment, pose a significant suicidality risk.
• Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune response
• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigate drug
• Any evidence of primary viral resistance to Nucleoside reverse transcriptase inhibitor (NRTIs), Non-nucleoside reverse transcriptase inhibitor (NNRTIs) based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result.
• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the subject's participation in the study of an investigational compound.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Trial

Experimental group

Description:

EFV 400mg

Treatment:

Drug: Efavirenz 400mg

Control

Active Comparator group

Description:

EFV 600mg

Treatment:

Drug: Efavirenz 600mg