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

NCT04513379 | Unknown Phase 3 DMC

• 1 other identifier: EDOSE
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

HIV Infections; Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week 48 Using the US Food and Drug Administration (FDA) Snapshot Algorithm

  The percentage of participants who were responders was assessed at the study Week 48 for participants randomized to receive at least one dose of study medication. Response was assessed using a modified FDA Snapshot algorithm

  Week 48

Secondary Outcomes (3)

• Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week24 Using the US Food and Drug Administration (FDA) Snapshot Algorithm

  Week 24

• Percentage of Participants Without Confirmed Virologic Withdrawal and Without Discontinuation Due to Treatment-related Reasons at Week 24 and Week 48

  Week 24 and Week 48

• Number of Participants With Tuberculosis (TB) Associated Immune Reconstitution Inflammatory Syndrome (IRIS)

  Week 12

Study Arms (2)

Trial

EXPERIMENTAL

EFV 400mg

Drug: Efavirenz 400mg

Control

ACTIVE COMPARATOR

EFV 600mg

Drug: Efavirenz 600mg

Interventions

Efavirenz 600mg DRUG

EFV 600 mg per day given orally

Control

Efavirenz 400mg DRUG

2 tablets of EFV 200 mg per day given orally

Trial

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Public Health Clinical Center: lead

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

efavirenz

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

Study Officials

• Jun Chen, M.D

  Shanghai Public Health Clinical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Chen, M.D

CONTACT

+86-21-37990333; qtchenjun@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shanghai Public Health Clinical Center

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 14, 2020
• Study Start: November 1, 2020
• Primary Completion: October 30, 2022
• Study Completion: January 31, 2023
• Last Updated: August 14, 2020

Record last verified: 2020-08