Efficacy of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients
Primary Purpose
HIV Infections, Tuberculosis
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Efavirenz 600mg
Efavirenz 400mg
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Trial
Control
Arm Description
EFV 400mg
EFV 600mg
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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.
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.
Full Information
NCT ID
NCT04513379
First Posted
August 12, 2020
Last Updated
August 12, 2020
Sponsor
Shanghai Public Health Clinical Center
1. Study Identification
Unique Protocol Identification Number
NCT04513379
Brief Title
Efficacy of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2020 (Anticipated)
Primary Completion Date
October 30, 2022 (Anticipated)
Study Completion Date
January 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Public Health Clinical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Tuberculosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Trial
Arm Type
Experimental
Arm Description
EFV 400mg
Arm Title
Control
Arm Type
Active Comparator
Arm Description
EFV 600mg
Intervention Type
Drug
Intervention Name(s)
Efavirenz 600mg
Intervention Description
EFV 600 mg per day given orally
Intervention Type
Drug
Intervention Name(s)
Efavirenz 400mg
Intervention Description
2 tablets of EFV 200 mg per day given orally
Primary Outcome Measure Information:
Title
Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week 48 Using the US Food and Drug Administration (FDA) Snapshot Algorithm
Description
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
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week24 Using the US Food and Drug Administration (FDA) Snapshot Algorithm
Description
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
Time Frame
Week 24
Title
Percentage of Participants Without Confirmed Virologic Withdrawal and Without Discontinuation Due to Treatment-related Reasons at Week 24 and Week 48
Description
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.
Time Frame
Week 24 and Week 48
Title
Number of Participants With Tuberculosis (TB) Associated Immune Reconstitution Inflammatory Syndrome (IRIS)
Description
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.
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Chen, M.D
Phone
+86-21-37990333
Ext
3222
Email
qtchenjun@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Chen, M.D
Organizational Affiliation
Shanghai Public Health Clinical Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Efficacy of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients
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