This double-blind, randomized controlled trial evaluates moxifloxacin vs isoniazid in daily treatment during the first two months of treatment with rifampin, pyrazinamide and ethambutol for sputum smear-positive pulmonary tuberculosis.

Condition	Intervention	Phase
Tuberculosis	Drug: Moxifloxacin (with rifampin, pyrazinamide, and ethambutol)	Phase II

Further Study Details: 

Primary Outcomes: • 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
Secondary Outcomes: • To compare the safety and tolerability of the moxifloxacin regimen to that of the isoniazid regimen; • 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; • To compare the proportion of patients with any Grade 3 or 4 adverse reactions; • To compare adverse events and 2-month culture conversion rates among HIV-infected patients vs. HIV-uninfected patients; • To compare the rates of treatment failure of the moxifloxacin regimen and the isoniazid regimen; • To determine whether there is delayed toxicity attributable to moxifloxacin (toxicity that becomes evident after the 8 weeks of moxifloxacin therapy)
Expected Total Enrollment:  410

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• 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 isoniazid, rifampin, fluoroquinolones, or any 2 study drugs 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.
• 14 or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding enrollment.
• 10 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 > 3.0 meq/L
• Negative pregnancy test (women of childbearing potential)

Exclusion Criteria:

• 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00144417

Stefan Goldberg, MD      404-639-5339    ssg3@cdc.gov

Arkansas
      Veterans Administration Medical Center of Arkansas, Little Rock,  Arkansas,  72205,  United States
California
      University of California at San Diego, San Diego,  California,  92103,  United States
      University of Southern California Medical Center, Los Angeles,  California,  90033,  United States
      University of California, San Francincisco, San Francisco,  California,  94110,  United States
Colorado
      Denver Public Health Department, Denver,  Colorado,  80204,  United States
District of Columbia
      Washington DC Veterans Administration Medical Center, Washington, DC,  District of Columbia,  20422,  United States
Georgia
      Emory University School of Medicine, Atlanta,  Georgia,  30303,  United States
Illinois
      Hines Veterans Administration Medical Center, Hines,  Illinois,  60141,  United States
      Northwestern University, Chicago,  Illinois,  60611,  United States
Maryland
      Johns Hopkins University School of Medicine, Baltimore,  Maryland,  21231,  United States
Massachusetts
      Boston University Medical Center, Boston,  Massachusetts,  02118,  United States
New Jersey
      New Jersey School of Medicine, Newark,  New Jersey,  07103,  United States
New York
      Columbia University, New York,  New York,  10032,  United States
      Harlem Hospital, Columbia University, New York,  New York,  10037,  United States
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States
Tennessee
      Veterans Administration Tennessee Valley Health Care System, Nashville,  Tennessee,  37232,  United States
Texas
      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
Washington
      Seattle-King County Health Department, Seattle,  Washington,  98104,  United States
Brazil
      Hopital Universitario Clementino Fraga Filho, Rio de Janeiro,  2194.590,  Brazil
Canada, British Columbia
      University of British Columbia, Vancouver,  British Columbia,  V5Z 4R4,  Canada
Canada, Manitoba
      University of Manitoba, Winnepeg,  Manitoba,  R3A 1R8,  Canada
Canada, Quebec
      Montreal Chest Institute, Montreal,  Quebec,  H2X 2P4,  Canada
South Africa, KwaZulu Natal
      Nelson R. Mandela School of Medicine, Durban,  KwaZulu Natal,  South Africa
Spain
      Agencia de Salut Publica, Barcelona,  08023,  Spain
Uganda
      Makerere University Medical School, Kampala,  Uganda

Study chairs or principal investigators

Richard E Chaisson, MD,  Study Chair,  Johns Hopkins University   
Susan E Dorman, MD,  Principal Investigator,  Johns Hopkins University   
John L Johnson, MD,  Principal Investigator,  Case Western Reserve University   

Study ID Numbers:  CDC-NCHSTP-4448
Last Updated:  September 2, 2005
Record first received:  September 1, 2005
ClinicalTrials.gov Identifier:  NCT00144417
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-06