A Pilot Study of Methodology to Rapidly Evaluate Drugs for Bactericidal Activity, Tolerance, and Pharmacokinetics in the Treatment of Pulmonary Tuberculosis Using Isoniazid and Levofloxacin
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
First received: November 2, 1999
Last updated: August 6, 2008
Last Verified: June 1995
History of Changes
To evaluate the methodology for rapidly determining the early bactericidal activity (EBA),
tolerance, and pharmacokinetics of isoniazid and levofloxacin in the treatment of pulmonary
Traditionally, in trials for treatment of TB, a new drug is administered in combination with two or more other antituberculous agents of known effectiveness over a long period of time. In this setting, it is difficult to determine the effect of any single drug or dose level. Development of new agents for the treatment of TB may be accelerated by a methodology in which a new agent could be evaluated for activity by administering it as a single agent over a short time period. This study utilizes a method to measure the amount of bacteria present each day in the lungs.
Drug : Isoniazid
Drug : Pyridoxine hydrochloride
Drug : Levofloxacin
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Methodology to Rapidly Evaluate Drugs for Bactericidal Activity, Tolerance, and Pharmacokinetics in the Treatment of Pulmonary Tuberculosis Using Isoniazid and Levofloxacin|
Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):
Traditionally, in trials for treatment of TB, a new drug is administered in combination with
two or more other antituberculous agents of known effectiveness over a long period of time.
In this setting, it is difficult to determine the effect of any single drug or dose level.
Development of new agents for the treatment of TB may be accelerated by a methodology in
which a new agent could be evaluated for activity by administering it as a single agent over
a short time period. This study utilizes a method to measure the amount of bacteria present
each day in the lungs.
An initial cohort of patients receive isoniazid (with pyridoxine) daily for 5 days. Sputum samples are collected daily for determination of the EBA (decline in colony-forming units/ml sputum). If the methodology is validated, additional patients are randomized to receive one of two doses of levofloxacin daily for 5 days, with determination of EBA. All patients are hospitalized for 2 days of baseline evaluation and 5 days of treatment.
|Ages Eligible for Study:||18 Years and older|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Allowed in all patients:
- Antacids if administered more than 2 hours before or after study drug.
- Anticonvulsant therapy if blood levels are monitored.
- Acceptable medications other than antacids if administered at least 2 hours before or 1 hour after study drug.
- Anticonvulsant therapy, theophylline, or warfarin if doses are monitored.
- Presumptive active pulmonary TB.
- No clinical evidence of central nervous system or miliary tuberculosis.
- Both HIV-positive and HIV-negative patients are eligible.
- Pregnant women may be enrolled in the isoniazid cohort only.
- Active or suspected MAI infection.
- Active or suspected hepatitis.
- Any other serious acute infection, diabetes, chronic obstructive pulmonary disease, malignancy requiring chemotherapy, or major organ dysfunction.
- Extreme illness or toxic appearance.
- Pregnancy (if entering the levofloxacin portion of the study).
- All standard TB therapies.
- Colony-stimulating factors.
- Disulfiram (patients receiving isoniazid).
- History of treatment-limiting intolerance or known hypersensitivity to isoniazid (in patients receiving isoniazid) or to quinolones (in patients receiving levofloxacin).
- Vomiting or diarrhea >= grade 2 at screening or within 2 days prior to screening.
- History of drug-resistant TB (in patients receiving isoniazid).
- Any prior treatment or prophylaxis for TB if enrolling on the isoniazid cohort.
- Any anti-TB drug within the past 12 weeks, including standard drugs against TB as well as clofazimine, rifabutin, and all quinolones and aminoglycosides.
- Corticosteroids, pentoxifylline, colony-stimulating factors, interferons, or interleukins within the past 12 weeks.
- Domicile, shelter, or prison exposure to a known case of MDR TB within the past 6 months.
- Residence in a specific domicile, shelter, or prison cell block within 6 months of a known outbreak of MDR TB.
- Hospitalization, within the past 6 months, on a medical service or unit in which
Allowed in isoniazid patients:
Allowed in levofloxacin patients:
Patients must have:
Patients with the following symptoms or conditions are excluded:
Patients with the following prior conditions are excluded:
Known risk factors for multi-drug resistant (MDR) TB, including:
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000778
Locations Show More
|United States, Alabama|
|Univ of Alabama at Birmingham|
|Birmingham, Alabama, United States, 352336505|
|United States, California|
|UCLA Med Ctr|
|Los Angeles, California, United States, 900951793|
|Harbor - UCLA Med Ctr|
|Torrance, California, United States, 90502|
|United States, Florida|
|Broward Gen Med Ctr|
|Fort Lauderdale, Florida, United States, 33316|
|Univ of Miami / Jackson Memorial Hosp|
|Miami, Florida, United States, 33136|
|United States, Illinois|
|Univ of Illinois|
|Chicago, Illinois, United States, 60622|
|United States, Louisiana|
|Tulane Univ Med School|
|New Orleans, Louisiana, United States, 701122699|
|United States, Texas|
|Univ of Texas Southwestern Med Ctr of Dallas|
|Dallas, Texas, United States, 75235|
|Univ TX Galveston|
|Galveston, Texas, United States, 77550|
|Baylor College of Medicine / Houston Veterans Adm Med Ctr|
|Houston, Texas, United States, 77030|
Sponsors and CollaboratorsNational Institute of Allergy and Infectious Diseases (NIAID)
|Study Chair:||Hafner R|
|Study Chair:||Cohn J|
|Study Chair:||Egorin M|
|Responsible Party:||National Institute of Allergy and Infectious Diseases (NIAID)|
|ClinicalTrials.gov Identifier:||NCT00000778 History of Changes|
|Other Study ID Numbers:||DATRI 008|
|Study First Received:||November 2, 1999|
|Last Updated:||August 6, 2008|
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):Isoniazid
AIDS-Related Opportunistic Infections
Acquired Immunodeficiency Syndrome
Colony Count, Microbial
Additional relevant MeSH terms:
Vitamin B 6
ClinicalTrials.gov processed this data on March 20, 2018
This information is provided by ClinicalTrials.gov.