NCT00396084.

Trial name or title	Randomized, open label, multiple dose Phase I study of the early bactericidal activity of linezolid, gatifloxacin, levofloxacin, and moxifloxacin in HIV‐non‐infected adults with Initial episodes of sputum smear‐positive pulmonary TB (DMID 01‐553)
Methods	—
Participants	Inclusion criteria: adults, male or female, aged 18 to 65 years; women with child‐bearing potential (not surgically sterilized or postmenopausal for < 1 year) must be using or agree to use an adequate method of birth control (condom: intravaginal spermicide (foams, jellies, sponge) and diaphragm: cervical cap or intrauterine device) during study drug treatment; newly diagnosed sputum smear‐positive pulmonary TB as confirmed by sputum AFB smear and chest x‐ray findings consistent with pulmonary TB; willing and able to provide informed consent; reasonably normal haemoglobin (≥ 8 gm/dL), renal function (serum creatinine < 2 mg/dL), hepatic function (serum AST < 1.5 times the upper limit of normal for the testing laboratory and total bilirubin < 1.3 mg/dL), and random blood glucose < 150 mg/dL. Exclusion criteria: HIV infection; weight < 75% of ideal body weight; presence of significant haemoptysis; patients who cough up frank blood (more than blood streaked sputum); pregnant or breastfeeding women and those who are not practicing birth control; significant respiratory impairment (respiratory rate > 35/min); clinical suspicion of disseminated TB or TB meningitis; presence of serious underlying medical illness (e.g. such as liver failure, renal failure, diabetes mellitus, chronic alcoholism, decompensated heart failure, haematologic malignancy) or patients receiving myelosuppressive chemotherapy; patients receiving any of monoamine oxidase inhibitors (phenelzine, tranylcypromine), adrenergic/serotonergic agonists such as pseudoephedrine and phenylpropanolamine (frequently found in cold and cough remedies), tricyclic antidepressants (amitriptyline, nortriptyline, protriptyline, doxepin, amoxapine, etc), antipsychotics (e.g. chlorpromazine and buspirone), serotonin re‐uptake inhibitors (fluoxetine, paroxetine, sertraline, etc), bupropion, agents known to prolong the QTc interval [erythromycin, clarithromycin, astemizole, type Ia (quinidine, procainamide, disopyramide) and III (amiodarone, sotalol) anti‐arrhythmics, carbamazepine, insulin, sulphonylureas, and meperidine; presence of QTc prolongation (> 450 msec) on baseline EKG; allergy or contraindication to use of study drugs; treatment with antituberculous medications or other antibiotics with known activity against M. tuberculosis during the preceding 6 months; inability to provide informed consent; total white blood cell count < 3000/mm3; platelet count < 150,000/mm3; patients with suspected drug‐resistant TB (e.g. contact to source patient with drug‐resistant TB, patients who have relapsed after previous treatment for TB); patients likely, in the opinion of the local investigator, to be unable to comply with the requirements of the study protocol.
Interventions	Participants will be randomized to receive gatifloxacin, levofloxacin, moxifloxacin, or isoniazid (control), and after these arms are enrolled, they will be randomized to receive either linezolid (600 mg once daily) or linezolid (600 mg twice daily) or isoniazid (control). After the initial treatment, all participants will receive 6 months of standard antituberculous treatment outside of the hospital.
Outcomes	1. Early bactericidal activity. 2. Extended early bactericidal activity. 3. Safety evaluations including clinical examination, complete blood counts, and serum total bilirubin, aspartate aminotransferase, and creatinine, and urinalysis will be followed to monitor for drug toxicity.
Starting date	February 2004
Contact information	John Johnson (jlj@po.cwru.edu)
Notes	Location: University of Espírito Santo, Vitória, Brazil Registration number: NCT00396084 Sponsors: National Institute of Allergy and Infectious Diseases (NIAID)