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.

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

525 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1998-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections Tuberculosis

Keywords

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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

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Cycloserine

Intervention Type DRUG

Ethionamide

Intervention Type DRUG

Capreomycin sulfate

Intervention Type DRUG

Aminosalicylic acid

Intervention Type DRUG

Streptomycin sulfate

Intervention Type DRUG

Ethambutol hydrochloride

Intervention Type DRUG

Amikacin sulfate

Intervention Type DRUG

Isoniazid

Intervention Type DRUG

Pyrazinamide

Intervention Type DRUG

Pyridoxine hydrochloride

Intervention Type DRUG

Levofloxacin

Intervention Type DRUG

Rifampin

Intervention Type DRUG

Clofazimine

Intervention Type DRUG

Eligibility Criteria

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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.)

Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Telzak E

Role: STUDY_CHAIR

Benson C

Role: STUDY_CHAIR

Chirgwin K

Role: STUDY_CHAIR

Sepkowitz K

Role: STUDY_CHAIR

Locations

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Cook County Hosp

Chicago, Illinois, United States

Site Status

Henry Ford Hosp

Detroit, Michigan, United States

Site Status

Interfaith Med Ctr

Brooklyn, New York, United States

Site Status

SUNY / Health Sciences Ctr at Brooklyn

Brooklyn, New York, United States

Site Status

Beth Israel Med Ctr

New York, New York, United States

Site Status

Clinical Directors Network of Region II

New York, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Saint Clare's Hosp and Health Ctr

New York, New York, United States

Site Status

Cornell Univ Med Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr

New York, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status