Comparison of Oral Fluconazole and Itraconazole for Progressive, Nonmeningeal Coccidioidomycosis

A Randomized, Double-Blind Trial

7 November 2000 | Volume 133 Issue 9 | Pages 676-686

Background: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis.

Objective: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: 7 treatment centers in California, Arizona, and Texas.

Patients: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections.

Intervention: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily.

Measurements: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline.

Results: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, –2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated.

Conclusions: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.

Author and Article Information

for the National Institute of Allergy and Infectious Diseases–Mycoses Study Group
From the Valley Fever Center for Excellence, Southern Arizona Veterans Affairs Health Care System, and University of Arizona, Tucson, Arizona; University of California, San Diego, San Diego, California; University of Alabama at Birmingham, Birmingham, Alabama; Kern Medical Center, Bakersfield, California; University of California, Los Angeles, and University of Southern California, Los Angeles, California; Santa Clara Valley Medical Center and Stanford University, San Jose, California; Visalia Medical Clinic, Visalia, California; University of Texas at San Antonio, San Antonio, Texas; and Maricopa Medical Center, Phoenix, Arizona.

Grant Support: In part by the National Institute of Allergy and Infectious Diseases (NO1-AI-15082, NO1-AI-65296), the University of California at San Diego General Clinical Research Center (MO1-RR00827), Pfizer Pharmaceutical Co., Janssen Research Foundation, U.S. Department of Veterans Affairs, and the Bank of Stockton (Stockton, California).

Requests for Single Reprints: John N. Galgiani, MD, Valley Fever Center for Excellence, 3601 South Sixth Avenue, Tucson, AZ 85723; e-mail, spherule{at}u.arizona.edu.

Current Author Addresses: Dr. Galgiani and Ms. Delgado: Valley Fever Center for Excellence, 3601 South Sixth Avenue, Tucson, AZ 85723.

Dr. Catanzaro: University of California at San Diego Medical Center, 200 West Arbor Drive, Suite 8374, San Diego, CA 92103.

Ms. Cloud and Ms. Flanigan: Comprehensive Cancer Unit, University of Alabama at Birmingham, 2001 Third Avenue South, Suite 1078, Birmingham, AL 35233.

Dr. Johnson: Division of Infectious Diseases, Kern Medical Center, 1830 Flower Street, Bakersfield, CA 93305.

Dr. Williams: Visalia Medical Clinic, 5400 West Hillsdale, Visalia, CA 93291-5114.

Drs. Mirels and Stevens: Division of Infectious Diseases, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128.

Dr. Nassar: Western Galilee Hospital, Nahariya, Israel 22100.

Dr. Lutz: 7335 North First Street, 103, Fresno, CA 93720-2926.

Dr. Sharkey: Division of Infectious Diseases, University of Texas Health Sciences Center, San Antonio, TX 78284.

Dr. Singh: Veterans Affairs Medical Center, South East Valley Extension, 6950 East Williams Field Road, Phoenix, AZ 85212-6033.

Dr. Larsen: Infectious Diseases, Pediatric Pavilion, 1129 North State Street, Los Angeles, CA 90033.

Dr. Rinaldi: Department of Pathology, University of Texas at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7750.

Author Contributions: Conception and design: J.N. Galgiani, A. Catanzaro; G.A. Cloud, D.A. Stevens, V.R. Singh, R.A. Larsen.

Analysis and interpretation of the data: J.N. Galgiani, G.A. Cloud, L.F. Mirels, D.A. Stevens, C. Flanigan, M.G. Rinaldi.

Drafting of the article: J.N. Galgiani, A. Catanzaro; G.A. Cloud, L.F. Mirels, D.A. Stevens, V.R. Singh, R.A. Larsen.

Critical revision of the article for important intellectual content: J.N. Galgiani, G.A. Cloud, P.L. Williams, L.F. Mirels, D.A. Stevens, V.R. Singh, R.A. Larsen.

Final approval of the article: J.N. Galgiani, A. Catanzaro, G.A. Cloud, L.F. Mirels, J.E. Lutz, D.A. Stevens, V.R. Singh, R.A. Larsen, C. Flanigan.

Provision of study materials or patients: J.N. Galgiani, A. Catanzaro, R.H. Johnson, P.L. Williams, L.F. Mirels, J.E. Lutz, D.A. Stevens, P.K. Sharkey, V.R. Singh, R.A. Larsen.

Statistical expertise: G.A. Cloud.

Obtaining of funding: J.N. Galgiani, D.A. Stevens.

Administrative, technical, or logistic support: J.N. Galgiani, L.F. Mirels, F. Nassar, D.A. Stevens, K.L. Delgado.

Collection and assembly of data: J.N. Galgiani, G.A. Cloud, L.F. Mirels, F. Nassar, J.E. Lutz, D.A. Stevens, V.R. Singh, R.A. Larsen, K.L. Delgado, M.G. Rinaldi.