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.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000778
First received: November 2, 1999
Last updated: August 6, 2008
Last verified: June 1995
  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 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
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

Resource links provided by NLM:


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

Additional Information:
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)

ClinicalTrials.gov Identifier: NCT00000778     History of Changes
Other Study ID Numbers: DATRI 008
Study First Received: November 2, 1999
Last Updated: August 6, 2008
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Tuberculosis, Pulmonary
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Isoniazid
Levofloxacin
Ofloxacin
Pyridoxine
Vitamin B 6
Pyridoxal
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014