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.”

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.

Study Type: Interventional

Study Design: Treatment, Safety Study

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.

Intervention(s) in this Clinical Trial

• 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

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.)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 13 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Telzak E Study Chair   

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00000796

Study ID Number: ACTG 238

ClinicalTrials.gov Identifier: NCT00000796

Health Authority: United States: Federal Government

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