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.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000796

Collaborator

(none)

525

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
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	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

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.

Actual Study Completion Date :

Oct 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Cook County Hosp	Chicago	Illinois	United States	60612
2	Henry Ford Hosp	Detroit	Michigan	United States	48202
3	Bronx Lebanon Hosp Ctr	Bronx	New York	United States	10456
4	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York	United States	10461
5	Comprehensive Health Care Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
6	Montefiore Drug Treatment Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
7	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
8	Samaritan Village Inc / Bronx Municipal Hosp	Bronx	New York	United States	10461
9	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10465
10	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10467
11	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10467
12	Interfaith Med Ctr	Brooklyn	New York	United States	112032098
13	SUNY / Health Sciences Ctr at Brooklyn	Brooklyn	New York	United States	112032098
14	Beth Israel Med Ctr	New York	New York	United States	10003
15	Clinical Directors Network of Region II	New York	New York	United States	10011
16	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
17	Saint Clare's Hosp and Health Ctr	New York	New York	United States	10019
18	Cornell Univ Med Ctr	New York	New York	United States	10021
19	Mount Sinai Med Ctr	New York	New York	United States	10029
20	Columbia Presbyterian Med Ctr	New York	New York	United States	100323784
21	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York	United States	10037