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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

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ClinicalTrials.gov Identifier: NCT00000778
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : August 8, 2008
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 2, 1999
First Posted Date  ICMJE August 31, 2001
Last Update Posted Date August 8, 2008
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary

To evaluate the methodology for rapidly determining the early bactericidal activity (EBA), tolerance, and pharmacokinetics of isoniazid and levofloxacin in the treatment of pulmonary tuberculosis (TB).

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • HIV Infections
  • Tuberculosis
Intervention  ICMJE
  • Drug: Isoniazid
  • Drug: Pyridoxine hydrochloride
  • Drug: Levofloxacin
Study Arms  ICMJE Not Provided
Publications * El-Sadr WM, Perlman DC, Matts JP, Nelson E, Cohn D, Telzak E, Chirgwin K, Salomon N, Olibrice M, Hafner R. Outcome of an induction regimen for the treatment of HIV-related tuberculosis (TB): evaluation of the addition of a quinolone. Int Conf AIDS. 1996 Jul 7-12;11(1):327 (abstract no TuB2358)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
44
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria

Concurrent Medication:

Allowed in all patients:

  • Antacids if administered more than 2 hours before or after study drug.

Allowed in isoniazid patients:

  • Anticonvulsant therapy if blood levels are monitored.

Allowed in levofloxacin patients:

  • 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.

Patients must have:

  • Presumptive active pulmonary TB.
  • No clinical evidence of central nervous system or miliary tuberculosis.

NOTE:

  • Both HIV-positive and HIV-negative patients are eligible.

NOTE:

  • Pregnant women may be enrolled in the isoniazid cohort only.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • 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).

Concurrent Medication:

Excluded:

  • All standard TB therapies.
  • Clofazimine.
  • Rifabutin.
  • Quinolones.
  • Aminoglycosides.
  • Corticosteroids.
  • Pentoxifylline.
  • Colony-stimulating factors.
  • Interferons.
  • Interleukins.
  • Disulfiram (patients receiving isoniazid).

Patients with the following prior conditions are excluded:

  • 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).

Prior Medication:

Excluded:

  • 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.

Known risk factors for multi-drug resistant (MDR) TB, including:

  • 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 nosocomial transmission of MDR TB is known to have occurred.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00000778
Other Study ID Numbers  ICMJE DATRI 008
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Hafner R
Study Chair: Cohn J
Study Chair: Egorin M
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date June 1995

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP