A5349

Phase 3

• Conditions: Tuberculosis

• Registration Number: PACTR202005623677468
• Lead Sponsor: AIDS Clinical Trials Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-19
• Last Update Posted: 29 May 2023

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Suspected pulmonary tuberculosis plus one or both of the following: a) at least one
sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least
one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with
semi quantitative result of ‘medium’ or ‘high’ and rifamycin resistance not detected.
2) Age twelve (12) years or older
3) A verifiable address or residence location that is readily accessible for visiting, and
willingness to inform the study team of any change of address during the treatment
and follow-up period.
4) Women of child-bearing potential who are not surgically sterilized must agree to
practice a barrier method of contraception or abstain from heterosexual intercourse
during study drug treatment.
5) Documentation of HIV infection status.
6) For HIV-positive individuals, CD4 T cell count greater than or equal to 100
cells/mm3 based on testing performed at or within 30 days prior to study entry.
HIV-positive individuals will be enrolled in a staged approach as described
below:
a. Group 1 (EFV1”): receipt of efavirenz-based antiretroviral therapy
(ART) for a minimum of 30 days at the time of enrollment AND a
documented HIV viral load less than 200 copies/mL at or within 30 days
prior to study entry, OR
b. Group 2 (EFV2”): for HIV-positive individuals not on ART at
enrollment, planned initiation of efavirenz-based ART before or at study
week 8
7) Laboratory parameters done at or within 14 days prior to screening:
10
? Serum or plasma alanine aminotransferase (ALT) less than or equal to 3
times the upper limit of normal
? Serum or plasma total bilirubin less than or equal to 2.5 times the upper
limit of normal
? Serum or plasma creatinine level less than or equal to 2 times the upper
limit of normal
? Serum or plasma potassium level greater than or equal to 3.5 meq/L
? Hemoglobin level of 7.0 g/dL or greater
? Platelet count of 100,000/mm3 or greater
8) For all women who are not surgically sterilized or who do not meet the study
definition of post-menopausal, a negative pregnancy test at or within seven (7)
days prior to screening
9) Karnofsky score greater than or equal to 60
10)Written informed consent
The study will provide study participants with counselling on the importance of contraception.
Participants will be provided for with condoms and those who need other forms of barrier
contraception will be referred to the appropriate care givers prior to starting study treatment.

Exclusion Criteria

1)Pregnant or breast-feeding
2) Unable to take oral medications
3) Previously enrolled in this study
4) Received any investigational drug in the past 3 months
5) More than five (5) days of treatment directed against active tuberculosis within 6
months preceding initiation of study drugs
6) More than five (5) days of systemic treatment with any one or more of the following
drugs within 30 days preceding initiation of study drugs: isoniazid, rifampin,
rifabutin, rifapentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin,
capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other
fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, paraaminosalicylic
acid, linezolid, clofazimine, delamanid or bedaquiline
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7) Known history of prolonged QT syndrome. Site clinicians will assess participants and
if there are signs and symptoms of heart disease or suggesting arrhythmias, then the
clinician will request for an ECG to rule out prolonged QT syndrome.
8) Suspected or documented tuberculosis involving the central nervous system and/or
bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis
9) Current or planned use within six months following enrollment of one or more of the
following medications: HIV protease inhibitors, HIV integrase inhibitors, HIV entry
and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors other than
efavirenz, quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone,
or terfenadine. Individuals who are currently taking efavirenz-based antiretroviral
treatment or for whom initiation of efavirenz-based antiretroviral treatment is planned
within 17 weeks following enrollment may participate, as per Section 8.3.10.
10) Weight less than 40.0 kg
11) Known allergy or intolerance to any of the study medications
12) Individuals will be excluded from enrollment if, at the time of enrollment, their M.
tuberculosis isolate is already known to be re

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
TB disease-free survival at twelve months after study treatment assignment

Secondary Outcome Measures

Name	Time	Method
Discontinuation of assigned treatment for a reason other than microbiological ineligibility