A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDRTB) in HIV-Infected Patients.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000796
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain.

Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.


Condition Intervention
HIV Infections
Tuberculosis
Drug: Cycloserine
Drug: Ethionamide
Drug: Capreomycin sulfate
Drug: Aminosalicylic acid
Drug: Streptomycin sulfate
Drug: Ethambutol hydrochloride
Drug: Amikacin sulfate
Drug: Isoniazid
Drug: Pyrazinamide
Drug: Pyridoxine hydrochloride
Drug: Levofloxacin
Drug: Rifampin
Drug: Clofazimine

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDRTB) in HIV-Infected Patients.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 525
Study Completion Date: October 1998
Detailed Description:

Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.

Patients are asked a series of questions to determine epidemiologic factors that may be predictive of MDRTB. Patients who are determined to be at low risk for MDRTB will be referred to another TB treatment protocol (ACTG 222), if appropriate. Patients suspected of having primary or acquired MDRTB or those with confirmed MDRTB will be offered a regimen of anti-TB therapy from a hierarchically ordered list of drugs, based on the patient's resistance status (suspect primary MDRTB, suspect acquired MDRTB, or confirmed MDRTB). The hierarchical list is as follows: isoniazid, rifampin, ethambutol, streptomycin, levofloxacin, ethionamide, cycloserine, capreomycin, aminosalicylic acid, and clofazimine. Treatment will be administered daily for at least 6 months, then on an intermittent schedule at the clinician's discretion. Patients with confirmed MDRTB (defined as known resistance to at least isoniazid and rifampin within 6 months prior to study entry) will receive a minimum of 18 months of treatment following sputum culture conversion. Follow-up is performed every 4 weeks for 8 weeks, and then every 8 weeks.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients must have:

  • Working diagnosis of HIV infection.
  • Working diagnosis of pulmonary TB.

Per 08/02/94 amendment, patients with confirmed MDRTB or known susceptibilities for the current episode at baseline are not eligible for the epidemiologic study only.

FOR TREATMENT PILOT:

  • Positive sputum AFB smear (or a positive sputum culture for TB within 6 months prior to study entry).
  • Assessment of suspect primary, suspect acquired, AND/OR confirmed MDRTB.
  • Life expectancy of at least 2 weeks.
  • Age >= 18 years for suspect MDRTB. Age >= 13 years for confirmed MDRTB.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Known hypersensitivity or resistance to quinolones.
  • Other disorders or conditions for which the study drugs are contraindicated.

Prior Medication:

Excluded:

  • More than 6 weeks total therapy within 3 months prior to study entry using three or more drugs effective against the isolates. (Per 08/02/94 amendment, patients from protocol ACTG 222/CPCRA 019 who have MDRTB are eligible for rollover to this study regardless of treatment duration on ACTG 222/CPCRA 019.)
  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: NCT00000796

Locations
United States, Illinois
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, Michigan
Henry Ford Hosp
Detroit, Michigan, United States, 48202
United States, New York
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Comprehensive Health Care Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10456
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
Interfaith Med Ctr
Brooklyn, New York, United States, 112032098
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Beth Israel Med Ctr
New York, New York, United States, 10003
Cornell Univ Med Ctr
New York, New York, United States, 10021
Clinical Directors Network of Region II
New York, New York, United States, 10011
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
Mount Sinai Med Ctr
New York, New York, United States, 10029
Columbia Presbyterian Med Ctr
New York, New York, United States, 100323784
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
Sponsors and Collaborators
Investigators
Study Chair: Telzak E
Study Chair: Benson C
Study Chair: Chirgwin K
Study Chair: Sepkowitz K
  More Information

Additional Information:
Publications:
Telzak EE, Chirgwin K, Nelson E, Matts J, Benson C, Sepkowitz K, Perlman D, El-Sadr W. Predictors for multidrug-resistant tuberculosis (MDRTB) among HIV-infected patients and response to specific MDRTB drug regimens. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:184 (abstract no 647)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000796     History of Changes
Other Study ID Numbers: ACTG 238, CPCRA 026, 11215
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Isoniazid
Tuberculosis, Pulmonary
Pyrazinamide
Pyridoxine
Ofloxacin
Rifampin
AIDS-Related Opportunistic Infections
Drug Therapy, Combination
Ethambutol
Clofazimine
Acquired Immunodeficiency Syndrome
Amikacin
Drug Resistance, Microbial
Cycloserine
Capreomycin Sulfate
Ethionamide
Aminosalicylic Acids
Streptomycin
p-Aminosalicylic Acid

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
Aminosalicylic Acid
Capreomycin
Cycloserine
Ethambutol
Ethionamide
Isoniazid
Pyrazinamide
Rifampin
Amikacin
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on September 14, 2014