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.

HIV Infections Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000796
• Other study ID #: ACTG 238
• Secondary ID: CPCRA 02611215
• Status: Completed
• Phase: N/A
• Est. completion date: October 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 525
• Est. completion date: October 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• Cycloserine

• Ethionamide

• Capreomycin sulfate

• Aminosalicylic acid

• Streptomycin sulfate

• Ethambutol hydrochloride

• Amikacin sulfate

• Isoniazid

• Pyrazinamide

• Pyridoxine hydrochloride

• Levofloxacin

• Rifampin

• Clofazimine

Locations

Country	Name	City	State
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Comprehensive Health Care Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Drug Treatment Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York
United States	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Samaritan Village Inc / Bronx Municipal Hosp	Bronx	New York
United States	Interfaith Med Ctr	Brooklyn	New York
United States	SUNY / Health Sciences Ctr at Brooklyn	Brooklyn	New York
United States	Cook County Hosp	Chicago	Illinois
United States	Henry Ford Hosp	Detroit	Michigan
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Clinical Directors Network of Region II	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Saint Clare's Hosp and Health Ctr	New York	New York

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

References & Publications (1)

Telzak EE, Chirgwin KD, Nelson ET, Matts JP, Sepkowitz KA, Benson CA, Perlman DC, El-Sadr WM. Predictors for multidrug-resistant tuberculosis among HIV-infected patients and response to specific drug regimens. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG), National Institutes for Health. Int J Tuberc Lung Dis. 1999 Apr;3(4):337-43. — View Citation