ClinicalTrials.gov
 Home    Search    Study Topics    Glossary  
 

  Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
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

This study has been completed.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000778
  Purpose

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.


Condition Intervention Phase
HIV Infections
Tuberculosis
Drug: Isoniazid
Drug: Pyridoxine hydrochloride
Drug: Levofloxacin
Phase I

MedlinePlus related topics:   AIDS    Tuberculosis   

Drug Information available for:   Vitamin B 6    5-Hydroxy-6-methyl-3,4-pyridinedimethanol hydrochloride    Pyridoxine    Levofloxacin    Ofloxacin    Ofloxacin hydrochloride    Isoniazid    Ftivazide   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Pharmacokinetics Study
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):

Estimated Enrollment:   44

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.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

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.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000778

Locations
United States, Alabama
Univ of Alabama at Birmingham    
      Birmingham, Alabama, United States, 352336505
United States, California
Harbor - UCLA Med Ctr    
      Torrance, California, United States, 90502
UCLA Med Ctr    
      Los Angeles, California, United States, 900951793
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 Collaborators

Investigators
Study Chair:     Hafner R    
Study Chair:     Cohn J    
Study Chair:     Egorin M    
  More Information


Click here for more information about Isoniazid  This link exits the ClinicalTrials.gov site
 

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)
 

Study ID Numbers:   DATRI 008
First Received:   November 2, 1999
Last Updated:   August 6, 2008
ClinicalTrials.gov Identifier:   NCT00000778
Health Authority:   United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Isoniazid  
Tuberculosis, Pulmonary  
Pyridoxine  
Ofloxacin  
AIDS-Related Opportunistic Infections  
Drug Evaluation
Acquired Immunodeficiency Syndrome
Sputum
Colony Count, Microbial

Study placed in the following topic categories:
Bacterial Infections
Opportunistic Infections
Sexually Transmitted Diseases, Viral
Ofloxacin
Acquired Immunodeficiency Syndrome
Vitamin B 6
Immunologic Deficiency Syndromes
Virus Diseases
Gram-Positive Bacterial Infections
Respiratory Tract Infections
Respiratory Tract Diseases
HIV Infections
Tuberculosis, pulmonary
Lung Diseases
Tuberculosis, Pulmonary
AIDS-Related Opportunistic Infections
Sexually Transmitted Diseases
Mycobacterium Infections
Pyridoxine
Tuberculosis
Retroviridae Infections
Isoniazid

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Vitamin B Complex
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Growth Substances
Antilipemic Agents
Physiological Effects of Drugs
Anti-Infective Agents, Urinary
Enzyme Inhibitors
Renal Agents
Infection
Actinomycetales Infections
Pharmacologic Actions
Anti-Bacterial Agents
Vitamins
Therapeutic Uses
Lentivirus Infections
Micronutrients
Antitubercular Agents
Nucleic Acid Synthesis Inhibitors
Fatty Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 03, 2008




Links to all studies - primarily for crawlers