Ignite Creation Date:
2024-05-05 @ 5:09 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00396084
Status:
COMPLETED
Last Update Posted:
2018-11-08
First Post:
2006-11-03
Brief Title:
Early Bactericidal Activity of Linezolid Gatifloxacin Levofloxacin Isoniazid INH and Moxifloxacin in HIV Negative Adults With Initial Episodes of Sputum Smear-Positive Pulmonary Tuberculosis
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official 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 Tuberculosis
Status:
COMPLETED
Status Verified Date:
2010-03-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the ability of 4 antibiotics to kill the bacteria that cause tuberculosis TB The antibiotics to be studied are linezolid gatifloxacin levofloxacin and moxifloxacin All are approved by the Brazilian health authorities to treat infections caused by germs other than TB Seventy human immunodeficiency virus HIV-negative adults aged 18-65 years who have been newly diagnosed with pulmonary lung TB will participate in this study Study volunteers will be given one of the 4 study drugs or a comparison antibiotic Isoniazid which has been used around the world as a standard of care treatment for TB Volunteers will stay in the hospital for 10 days and be given a study antibiotic 7 of those days Blood and saliva samples will be taken Six weeks later volunteers will return for a final health check All volunteers will receive 6 months of standard tuberculosis treatment
Detailed Description:
Multi-drug resistant tuberculosis now affects all regions of the world and is a significant concern for national tuberculosis TB control programs The development and testing of new drugs and new classes of drugs and immunotherapeutic agents are vital elements in the global response to this challenge The fluoroquinolones and oxazolidinones represent two promising classes of drugs that show activity against Mycobacterium tuberculosis MTB This study is a randomized open label multiple dose phase I clinical trial to evaluate the early bactericidal activity EBA of gatifloxacin levofloxacin moxifloxacin and linezolid compared with an isoniazid INH control arm in patients with newly-diagnosed sputum smear-positive pulmonary tuberculosis TB Secondary study objectives are to compare results of sputum MTB messenger ribonucleic acid mRNA clearance with results of a standard EBA study change in sputum viable counts colony forming units CFU compare the rate of clearance of sputum cytokine proteins with results of a standard EBA assay CFU determine the pharmacokinetics PK of the study drugs in patients with smear-positive pulmonary TB and demonstrate that lack of EBA activity is not due to low serum drug concentrations Seventy human immunodeficiency virus HIV negative adults aged 18-65 years who have been newly diagnosed with pulmonary TB will be enrolled and admitted to the Centro de Pesquisa Clinical Research Ward at the Hospital Universitario Cassiano Antonio de Moraes of the Universidade Federal do Espírito Santo in Vitória The subjects will be randomized to receive gatifloxacin levofloxacin moxifloxacin or INH 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 INH control During the inpatient stay study drugs will be given for 7 days following a 2-day drug-free period when baseline sputum bacillary counts will be measured The 7-day duration of the study drug phase will allow measurement of sputum bactericidal activity both during the first 2 days of study drug administration and between days 2 and 7 of study drug administration to gain additional information on the possible sterilizing activity of the drugs The extended nature of these EBA studies will allow assessment of this possibility in the study drugs that would be missed if a shorter EBA study was performed Sputum specimens will be collected for 2 days prior to initiation of study drug in order to establish a baseline quantitative culture result and then specimens will be collected daily thereafter Sputum specimens will be processed to evaluate changes in mycobacterial mRNAproteins and cytokine proteins PK studies will be performed after 5 days of study drug administration Day 5 Safety evaluations including clinical examination complete blood counts and serum total bilirubin aspartate aminotransferase AST creatinine and urinalysis will be followed to monitor for drug toxicity Drug susceptibility testing will be performed on an initial sputum isolate and will be repeated after completion of 7 days of study drugs and on isolates from patients with positive sputum cultures at the day 42 study visit to assess for the development of acquired drug resistance Isolates will be tested against INH rifampicin pyrazinamide ethambutol and the subjects assigned study drug Patients who are found to be resistant to their assigned study drug at baseline will not be analyzable After the initial treatment all subjects will receive 6 months of standard TB treatment outside of the hospital
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None