Linezolid to Treat Extensively-Drug Resistant Tuberculosis

This is an interventional treatment trial for Pulmonary Tuberculosis focused on measuring XDR-TB, Linezolid, Drug Resistance, Computed Tomography, Pharmacokinetics, Tuberculosis, Drug Resistance Tuberculosis, MDR-TB Read More

• INCLUSION CRITERIA:

Males and females age 20 and above

Documented pulmonary tuberculosis at screening

Radiographic evidence of tuberculous disease of the lung(s)

History of chronic, AFB positive sputum smears and culture positive TB

Mycobacterium species identification as Mycobacterium tuberculosis

Confirmed resistance to INH, RIF, kanamycin, ofloxacin, and moxifloxacin by genotypic or phenotypic testing OR subjects with documented failure to respond to treatment despite DST susceptibility

Failure to respond (after at least 6 months) to a anti-TB drug regimen including any known active agents

Willingness to be an inpatient until 2 consecutive AFB-negative sputum smears

When an outpatient, willing to come back for weekly tests and scheduled follow-up visits

Willingness to have samples stored

Ability and willingness to give written or oral informed consent

EXCLUSION CRITERIA:

Subjects below 20 years of age

Subjects who have previously been on LZD

Women of childbearing potential, who are pregnant, breast feeding, or unwilling to avoid pregnancy (i.e., the use of appropriate contraception including oral and subcutaneous implantable hormonal contraceptives, condoms, diaphragm, intrauterine device (IUD), or abstinence from sexual intercourse). [Note: Prospective female participants of childbearing potential must have negative pregnancy test (urine) within 48 hours prior to study entry.]

Men who are unwilling to use contraceptives or practice abstinence

People with any of the following in their current medical assessments:

Absolute neutrophil count less than 1000 cells/mL

White blood cell count (WBC) less than 3.0 X 10(3)/microL

Hemoglobin less than 7.0 g/dL

Platelet count less than 75,000 cells/mm(3)

Serum creatinine greater than 2.0 mg/dL

Aspartate aminotransferase (AST or SGOT) greater than 100 IU/L

Alanine aminotransferase (ALT or SGPT) greater than 100 IU/L

Total bilirubin greater than 2.0 mg/dL

Moderate or severe peripheral or optical neuropathy (or a history of)

HIV-1 or HIV-2 infection

Systemic lupus erythematosus, rheumatoid arthritis, or other connective tissue disease

Patients who, in the investigator's judgment, are too ill to participate in the study

History of allergy or serious adverse reaction to the LZD formulation used in this study

Patients with anticipated surgical intervention

The use of any of the following drugs within 30 days prior to study or anticipated use of these drugs within the next 60 days: (Please not, bronchodilators and cough syrup (or similar cough medicines) are allowed before and during the study if blood pressure is monitored regularly, per Contraindications, p.12, of the Zyvox Package Insert.)

Selective serotonin reuptake inhibitors (SSRIs)

Monoamine oxidase inhibitors (MAOIs)

Systemic cancer chemotherapy

Systemic corticosteroids

Systemic investigational agents

Antiretroviral medications

Growth factors

HIV vaccines

Immune globulin

Interleukins

Interferons

The need for ongoing therapy with antidepressants (SSRI, MAOI), hydroxyzine, dopaminergic agents (such as Sinemet, dopamine, and dobutamine), lithium, cyclosporine, tacrolimus, sirolimus, and levodopa (such as sinemet) while on study drug

Any other serious systemic illness requiring treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy for at least 14 days prior to study entry

Patients who the physician has reason to believe may have been non-compliant in the previous 12 months of treatment

SUBSTUDY ELIGIBILITY CRITERIA

INCLUSION CRITERIA:

Subjects who meet the inclusion criteria for main study are eligible for the substudy.

EXCLUSION CRITERIA:

Exclusion criteria for main study apply to the substudy with the exception that subjects with uncontrolled diabetes mellitus will be excluded from the substudy. The study physician may decide that a patient is healthy enough to participate in the main study but not the sub-study.