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	Treatment or 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

Further Study Details: 

Expected Total Enrollment:  525

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

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.)

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

Study chairs or principal investigators

Telzak E,  Study Chair
Benson C,  Study Chair
Chirgwin K,  Study Chair
Sepkowitz K,  Study Chair

Study ID Numbers:  ACTG 238; CPCRA 026
Record last reviewed:  November 1998
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000796
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08