Clinical trial NCT00140309: TBTC Study 27: Moxifloxacin vs Ethambutol for TB Treatment
Official title: TBTC Study 27: An Evaluation of the Activity and Tolerability of Moxifloxacin During the First Two Months of Treatment for Pulmonary Tuberculosis--A Double-Blind, Randomized, Multicenter Study by the Tuberculosis Trials Consortium
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis, Pulmonary
Keywords: TB
Pulmonary Tuberculosis
Tuberculosis
Pulmonary TB
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
First posted: 2005-09-01
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This study is a placebo-controlled factorial study, randomized to study drug (moxifloxacin vs. ethambutol) and treatment frequency (daily vs. thrice weekly after an initial two weeks of daily therapy) during the first two months of standard treatment (with isoniazid, rifampin, and pyrazinamide) for sputum smear-positive pulmonary tuberculosis.

Detailed description: The primary objective of this Phase II clinical trial is to compare the safety and microbiological activity of a moxifloxacin-containing regimen (isoniazid, rifampin, pyrazinamide, moxifloxacin \[HRZMoxi\]) to a control regimen (isoniazid, rifampin, pyrazinamide, ethambutol \[HRZE\]) in the first two months of treatment of sputum smear-positive pulmonary tuberculosis. In addition, the study will evaluate whether intermittent administration (thrice-weekly after the first 2 weeks) of these regimens affects their tolerability and microbiological activity. The assessment of microbiological activity will be sputum culture-conversion. Improved sputum culture conversion after 2 months of treatment with a moxifloxacin-containing regimen would support phase 3 clinical trials of moxifloxacin in treatment regimens of less than the current 6 month standard regimens.

Eligibility criteria: Inclusion Criteria:

1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained sputum smear - patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to rifampin will be discontinued from the study, but followed for 14 days to detect late toxicities from study therapy. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment.
2. Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 6 months prior to enrollment
3. 7 or fewer days of tuberculosis therapy in the 6 months preceding enrollment
4. Age \> 18 years
5. Karnofsky score of at least 60
6. Signed informed consent
7. Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual sex.
8. Laboratory parameters within 14 days of enrollment:

   * Serum amino aspartate transferase (AST) activity less than 3 times the upper limit of normal
   * Serum total bilirubin level less than 2.5 times upper limit of normal
   * Serum creatinine level less than 2 times upper limit of normal
   * Hemoglobin level of at least 7.0 g/dL
   * Platelet count of at least 50,000/mm3
   * Serum potassium \> 3.0 meq/L
   * Negative pregnancy test (for women of childbearing potential)

Exclusion Criteria:

1. Breast-feeding
2. Known intolerance to any of the study drugs
3. Known allergy to any fluoroquinolone antibiotic
4. Current or planned therapy during the first 2 months of tuberculosis treatment using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy)
5. Current or planned antiretroviral therapy during the first 2 months of tuberculosis treatment
6. History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the first 2 months of tuberculosis treatment.
7. Pulmonary silicosis

Primary outcomes:
measure: Two-month culture conversion
measure: Serious Adverse Event
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Medical Center
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Denver Public Health Department
state: Colorado
city: Washington DC
country: United States
facility: Washington DC Veterans Administration Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Hines
country: United States
facility: Hines Vetrans Administration Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Newark
country: United States
facility: New Jersey School of Medicine
state: New Jersey
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Harlem Hospital Center
state: New York
city: Nashville
country: United States
facility: Veterans Administration Tennessee Valley Health Care System
state: Tennessee
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: Houston
country: United States
facility: Houston Veterans Administration Medical Center
state: Texas
city: San Antonio
country: United States
facility: Audie L Murphy Memorial Veterans Administration Medical Center
state: Texas
city: Seattle
country: United States
facility: Seattle-King County Health Department
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Montreal
country: Canada
facility: Montreal Chest Institute
state: Quebec
city: Durban
country: South Africa
facility: Nelson R Mandela School of Medicine
state: KwaZulu Natal
city: Kampala
country: Uganda
facility: Makerere University Medical School
Study officials:
affiliation: Denver Public Health Department
name: William Burman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Richard E Chaisson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burman WJ, Goldberg S, Johnson JL, Muzanye G, Engle M, Mosher AW, Choudhri S, Daley CL, Munsiff SS, Zhao Z, Vernon A, Chaisson RE. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med. 2006 Aug 1;174(3):331-8. doi: 10.1164/rccm.200603-360OC. Epub 2006 May 4.
citation: Zhang N, Savic RM, Boeree MJ, Peloquin CA, Weiner M, Heinrich N, Bliven-Sizemore E, Phillips PPJ, Hoelscher M, Whitworth W, Morlock G, Posey J, Stout JE, Mac Kenzie W, Aarnoutse R, Dooley KE; Tuberculosis Trials Consortium (TBTC) and Pan African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA) Networks. Optimising pyrazinamide for the treatment of tuberculosis. Eur Respir J. 2021 Jul 20;58(1):2002013. doi: 10.1183/13993003.02013-2020. Print 2021 Jul.