TBTC Study 27: Moxifloxacin vs Ethambutol for TB Treatment

Tuberculosis, Pulmonary Clinical Trial

Official title:

TBTC Study 27: An Evaluation of the Activity and Tolerability of Moxifloxacin During the First Two Months of Treatment for Pulmonary Tuberculosis--A Double-Blind, Randomized, Multicenter Study by the Tuberculosis Trials Consortium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140309
• Other study ID #: CDC-NCHSTP-3716
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2005
• Last updated: March 16, 2007
• Start date: July 2003
• Est. completion date: December 2005

Study information

• Verified date: March 2007
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is a placebo-controlled factorial study, randomized to study drug (moxifloxacin vs. ethambutol) and treatment frequency (daily vs. thrice weekly after an initial two weeks of daily therapy) during the first two months of standard treatment (with isoniazid, rifampin, and pyrazinamide) for sputum smear-positive pulmonary tuberculosis.

Description:

The primary objective of this Phase II clinical trial is to compare the safety and microbiological activity of a moxifloxacin-containing regimen (isoniazid, rifampin, pyrazinamide, moxifloxacin [HRZMoxi]) to a control regimen (isoniazid, rifampin, pyrazinamide, ethambutol [HRZE]) in the first two months of treatment of sputum smear-positive pulmonary tuberculosis. In addition, the study will evaluate whether intermittent administration (thrice-weekly after the first 2 weeks) of these regimens affects their tolerability and microbiological activity. The assessment of microbiological activity will be sputum culture-conversion. Improved sputum culture conversion after 2 months of treatment with a moxifloxacin-containing regimen would support phase 3 clinical trials of moxifloxacin in treatment regimens of less than the current 6 month standard regimens.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained sputum smear – patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to rifampin will be discontinued from the study, but followed for 14 days to detect late toxicities from study therapy. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment.

2. Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 6 months prior to enrollment

3. 7 or fewer days of tuberculosis therapy in the 6 months preceding enrollment

4. Age > 18 years

5. Karnofsky score of at least 60

6. Signed informed consent

7. Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual sex.

8. Laboratory parameters within 14 days of enrollment:

• Serum amino aspartate transferase (AST) activity less than 3 times the upper limit of normal

• Serum total bilirubin level less than 2.5 times upper limit of normal

• Serum creatinine level less than 2 times upper limit of normal

• Hemoglobin level of at least 7.0 g/dL

• Platelet count of at least 50,000/mm3

• Serum potassium > 3.0 meq/L

• Negative pregnancy test (for women of childbearing potential)

Exclusion Criteria:

1. Breast-feeding

2. Known intolerance to any of the study drugs

3. Known allergy to any fluoroquinolone antibiotic

4. Current or planned therapy during the first 2 months of tuberculosis treatment using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy)

5. Current or planned antiretroviral therapy during the first 2 months of tuberculosis treatment

6. History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the first 2 months of tuberculosis treatment.

7. Pulmonary silicosis

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• moxifloxacin (with isoniazid, rifampin, pyrazinamide)

Locations

Country	Name	City	State
Canada	Montreal Chest Institute	Montreal	Quebec
Canada	University of British Columbia	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg	Manitoba
South Africa	Nelson R Mandela School of Medicine	Durban	KwaZulu Natal
Uganda	Makerere University Medical School	Kampala
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Boston University Medical Center	Boston	Massachusetts
United States	Denver Public Health Department	Denver	Colorado
United States	University of North Texas Health Science Center	Fort Worth	Texas
United States	Hines Vetrans Administration Medical Center	Hines	Illinois
United States	Houston Veterans Administration Medical Center	Houston	Texas
United States	University of Southern California Medical Center	Los Angeles	California
United States	Veterans Administration Tennessee Valley Health Care System	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Harlem Hospital Center	New York	New York
United States	New York University School of Medicine	New York	New York
United States	New Jersey School of Medicine	Newark	New Jersey
United States	Audie L Murphy Memorial Veterans Administration Medical Center	San Antonio	Texas
United States	University of California at San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Seattle-King County Health Department	Seattle	Washington
United States	Washington DC Veterans Administration Medical Center	Washington DC	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention

Countries where clinical trial is conducted

United States,  Canada,  South Africa,  Uganda, 

References & Publications (1)

Burman WJ, Goldberg S, Johnson JL, Muzanye G, Engle M, Mosher AW, Choudhri S, Daley CL, Munsiff SS, Zhao Z, Vernon A, Chaisson RE. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med. 200 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Two-month culture conversion
Primary	Serious Adverse Event

External Links

•   Tuberculosis Trials Consortium (TBTC) web page