Pilot Randomized Study of Paromomycin (Aminosidine) vs Streptomycin for Uncomplicated Pulmonary Tuberculosis

FDA Office of Orphan Products Development

Status: Completed

Conditions: Tuberculosis, Pulmonary

Treatments: Drug: paromomycin; Drug: streptomycin

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT00004444

199/13445

UIC-FDR001167

Details and patient eligibility

About

OBJECTIVES: I. Compare the pharmacokinetics and early bactericidal activity of paromomycin (aminosidine) vs streptomycin for the treatment of uncomplicated pulmonary tuberculosis.

II. Compare the tolerability of these two drugs in these patients. III. Establish the relationships between achieved serum concentration, minimal inhibitory concentration, and early bactericidal activity of paromomycin and streptomycin.

Full description

PROTOCOL OUTLINE: This is a randomized study. Patients are randomized to one of three treatment arms. Patients in arms I and II receive one of two doses of paromomycin intramuscularly once a day for 3 days. Patients in arm III receive streptomycin intramuscularly once a day for 3 days. All patients then begin a course of standard therapy for tuberculosis.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Microbiologically proven uncomplicated pulmonary tuberculosis Positive direct sputum smear for acid-fast bacilli OR Presumptive diagnosis based on clinical and radiological findings
• No known risk factors for multidrug resistant tuberculosis (MDR TB) including: Domicile, shelter, or prison exposure to MDR TB within 6 months Residence in a specific domicile, shelter, or prison cell block within 6 months of a known outbreak of MDR TB Hospitalization, within 6 months, on a medical service or unit in which nosocomial transmission of MDR TB is known to have occurred
• No clinical evidence of CNS or miliary tuberculosis
• HIV seronegative

--Prior/Concurrent Therapy--

• Biologic therapy: At least 12 weeks since immune modulators (including colony-stimulating factors, interferons, or interleukins)
• Chemotherapy: No concurrent chemotherapy
• Endocrine therapy: At least 12 weeks since corticosteroids
• Other: At least 2 years since treatment or prophylaxis for tuberculosis At least 12 weeks since treatment with any drug with activity against tuberculosis, including: All standard drugs used for tuberculosis Clofazimine Rifabutin Quinolones Aminoglycosides At least 12 weeks since pentoxifylline

--Patient Characteristics--

• Hematopoietic: Absolute neutrophil count at least 1,000/mm3
• Renal: Creatinine clearance greater than 60 mL/min
• Pulmonary: No chronic obstructive pulmonary disease
• Other: Not pregnant Fertile patients must use effective contraception No history of intolerance or known hypersensitivity to aminoglycosides No known or suspected Mycobacterium avium complex infection No other serious, acute infection No diabetes No major organ dysfunction No malignancy requiring chemotherapy