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

HIV Infections Clinical Trial

Official title:

Efficacy and Safety of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients Receiving Rifampicin Based Anti-TB Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04513379
• Other study ID #: EDOSE
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 1, 2020
• Est. completion date: January 31, 2023

Study information

• Verified date: August 2020
• Source: Shanghai Public Health Clinical Center
• Contact: Jun Chen, M.D
• Phone: +86-21-37990333
• Email: qtchenjun[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: January 31, 2023
• Est. primary completion date: October 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• Efavirenz 600mg
EFV 600 mg per day given orally
• Efavirenz 400mg
2 tablets of EFV 200 mg per day given orally

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Public Health Clinical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week24 Using the US Food and Drug Administration (FDA) Snapshot Algorithm	The percentage of participants who were responders was assessed at the study Week 24 for participants randomized to receive at least one dose of study medication. Response was assessed using a modified FDA Snapshot algorithm	Week 24
Secondary	Percentage of Participants Without Confirmed Virologic Withdrawal and Without Discontinuation Due to Treatment-related Reasons at Week 24 and Week 48	Percentage of participants not meeting confirmed virologic withdrawal criteria nor discontinued due to treatment related reasons at the time of analysis at Week 24 (through Day 210) and Week 48 (through Day 350) is presented by treatment group.	Week 24 and Week 48
Secondary	Number of Participants With Tuberculosis (TB) Associated Immune Reconstitution Inflammatory Syndrome (IRIS)	Participants were monitored for signs and symptoms of TB-IRIS. Participants with IRIS symptoms in any adverse events or HIV associated. conditions were classified by the study investigators in the following categories as met criteria for TB-IRIS, possibly met criteria for TB-IRIS and suspected TB-IRIS but not possible to adjudicate.	Week 12