TBTC Study 28: Moxifloxacin Versus Isoniazid for TB Treatment
TBTC Study 28: Evaluation of a Moxifloxacin-based, Isoniazid-sparing Regimen for Tuberculosis Treatment
1 other identifier
interventional
433
6 countries
26
Brief Summary
This double-blind, randomized controlled trial evaluates moxifloxacin versus isoniazid in daily treatment during the first two months of treatment with rifampin, pyrazinamide and ethambutol for sputum smear-positive pulmonary tuberculosis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2006
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 1, 2005
CompletedFirst Posted
Study publicly available on registry
September 5, 2005
CompletedStudy Start
First participant enrolled
February 1, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2007
CompletedAugust 3, 2011
June 1, 2011
1.3 years
September 1, 2005
August 2, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
• To compare the culture-conversion rate at the end of the intensive phase of therapy of the moxifloxacin regimen vs. that of the isoniazid regimen
8 weeks
Secondary Outcomes (6)
To compare the safety and tolerability of the moxifloxacin regimen to that of the isoniazid regimen
8 weeks
To determine the time to culture-conversion of the moxifloxacin regimen and the isoniazid regimen using data from 2-, 4-, 6-, and 8-week cultures
8 weeks
To compare the proportion of patients with any Grade 3 or 4 adverse reactions
8 weeks
To compare adverse events and 2-month culture conversion rates among HIV-infected patients vs. HIV-uninfected patients
8 weeks
To compare the rates of treatment failure of the moxifloxacin regimen and the isoniazid regimen
6 months
- +1 more secondary outcomes
Study Arms (2)
HRZE
ACTIVE COMPARATORisoniazid, rifampin, pyrazinamide, ethambutol, moxifloxacin-placebo
MRZE
EXPERIMENTALmoxifloxacin, rifampin, pyrazinamide, ethambutol, isoniazid-placebo
Interventions
Eligibility Criteria
You may qualify if:
- Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated or induced sputum. Patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to (one or more) isoniazid, rifampin, fluoroquinolones, 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. Sputum must be expectorated or induced; smear results from respiratory secretions obtained by bronchoalveolar lavage or bronchial wash may not be used for assessment of study eligibility.
- 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. HIV testing does not need to be repeated if there is written documentation of a positive test (positive ELISA and Western Blot or a plasma HIV-RNA level greater than 5000 copies/ml) at any time in the past.
- (seven) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding enrollment.
- (seven) or fewer days of fluoroquinolone therapy in the 3 months preceding enrollment.
- Age \> 18 years
- Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix B).
- Signed informed consent
- Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
- Laboratory parameters done at, or \<14 days prior to, screening:
- Serum amino aspartate transferase (AST) activity ≤ 3 times the upper limit of normal
- Serum total bilirubin level ≤ 2.5 times the upper limit of normal
- Serum creatinine level ≤ 2 times the upper limit of normal
- Complete blood count with hemoglobin level of at least 7.0 g/dL
- Complete blood count with platelet count of at least 50,000/mm3
- Serum potassium \> 3.5 meq/L
- +1 more criteria
You may not qualify if:
- Breast-feeding
- Known intolerance to any of the study drugs
- Known allergy to any fluoroquinolone antibiotic
- Concomitant disorders or conditions for which moxifloxacin (MXF), isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
- Current or planned therapy during the intensive phase of therapy using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy).
- Current or planned antiretroviral therapy during the intensive phase of therapy.
- History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine during the intensive phase of therapy.
- Pulmonary silicosis
- Central nervous system TB
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Centers for Disease Control and Preventionlead
- Global Alliance for TB Drug Developmentcollaborator
- Bayercollaborator
Study Sites (26)
Veterans Administration Medical Center of Arkansas
Little Rock, Arkansas, 72205, United States
University of Southern California Medical Center
Los Angeles, California, 90033, United States
University of California at San Diego
San Diego, California, 92103, United States
University of California, San Francincisco
San Francisco, California, 94110, United States
Denver Public Health Department
Denver, Colorado, 80204, United States
Washington DC Veterans Administration Medical Center
Washington D.C., District of Columbia, 20422, United States
Emory University School of Medicine
Atlanta, Georgia, 30303, United States
Northwestern University
Chicago, Illinois, 60611, United States
Hines Veterans Administration Medical Center
Hines, Illinois, 60141, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21231, United States
Boston University Medical Center
Boston, Massachusetts, 02118, United States
New Jersey School of Medicine
Newark, New Jersey, 07103, United States
Columbia University
New York, New York, 10032, United States
Harlem Hospital, Columbia University
New York, New York, 10037, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Veterans Administration Tennessee Valley Health Care System
Nashville, Tennessee, 37232, United States
University of North Texas Health Science Center
Fort Worth, Texas, 76104, United States
Houston Veterans Administration Medical Center
Houston, Texas, 77030, United States
Audie L Murphy Memorial Veterans Administration Medical Center
San Antonio, Texas, 78284, United States
Seattle-King County Health Department
Seattle, Washington, 98104, United States
Hopital Universitario Clementino Fraga Filho
Rio de Janeiro, Rio de Janeiro, 2194.590, Brazil
University of Manitoba
Winnepeg, Manitoba, R3A 1R8, Canada
Montreal Chest Institute
Montreal, Quebec, H2X 2P4, Canada
Nelson R. Mandela School of Medicine
Durban, KwaZulu-Natal, South Africa
Agencia de Salut Publica
Barcelona, 08023, Spain
Makerere University Medical School
Kampala, Uganda
Related Publications (3)
Dorman SE, Johnson JL, Goldberg S, Muzanye G, Padayatchi N, Bozeman L, Heilig CM, Bernardo J, Choudhri S, Grosset JH, Guy E, Guyadeen P, Leus MC, Maltas G, Menzies D, Nuermberger EL, Villarino M, Vernon A, Chaisson RE; Tuberculosis Trials Consortium. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. Am J Respir Crit Care Med. 2009 Aug 1;180(3):273-80. doi: 10.1164/rccm.200901-0078OC. Epub 2009 Apr 30.
PMID: 19406981RESULTZhang 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.
PMID: 33542052DERIVEDMac Kenzie WR, Heilig CM, Bozeman L, Johnson JL, Muzanye G, Dunbar D, Jost KC Jr, Diem L, Metchock B, Eisenach K, Dorman S, Goldberg S. Geographic differences in time to culture conversion in liquid media: Tuberculosis Trials Consortium study 28. Culture conversion is delayed in Africa. PLoS One. 2011 Apr 11;6(4):e18358. doi: 10.1371/journal.pone.0018358.
PMID: 21494548DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Richard E Chaisson, MD
Johns Hopkins University
- PRINCIPAL INVESTIGATOR
Susan E Dorman, MD
Johns Hopkins University
- PRINCIPAL INVESTIGATOR
John L Johnson, MD
Case Western Reserve University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
Study Record Dates
First Submitted
September 1, 2005
First Posted
September 5, 2005
Study Start
February 1, 2006
Primary Completion
June 1, 2007
Study Completion
December 1, 2007
Last Updated
August 3, 2011
Record last verified: 2011-06