A Study to Compare the Use of Fluconazole as Continuous Therapy Versus Periodic Therapy in HIV-Positive Patients With Recurrent Thrush

Condition(s) targeted: Candidiasis, Oral; HIV Infections

Intervention: Fluconazole (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Mitchell Goldman, Study Chair
Scott G. Filler, Study Chair

The purpose of this study is to determine whether it is better to treat patients with fluconazole on a continuous basis to prevent thrush (yeast infection in the mouth) from coming back or to wait and treat each episode of thrush.

Fluconazole is one of the most commonly prescribed drugs to treat thrush and other yeast infections. However, the number of patients with fluconazole-resistant thrush is increasing, and it is not known whether continuous or intermittent use of fluconazole leads to greater resistance. Therefore, it is important to determine the most effective treatment strategy.

Official title: A Phase IV Randomized Study of the Use of Fluconazole as Chronic Suppressive Therapy Versus Episodic Therapy in HIV Positive Subjects With Recurrent Oropharyngeal Candidiasis

Study design: Treatment, Parallel Assignment, Efficacy Study

Detailed description: This study will evaluate two different management strategies for patients with advanced HIV infection who are at risk for recurrent and fluconazole-refractory oropharyngeal candidiasis. The treatment duration will be at least 24 months in order to evaluate the long-term effects of the treatment strategies on the development of fluconazole-refractory thrush. In addition to investigating antifungal treatment as it relates to fluconazole-refractory infections, the study will evaluate host factors and organism-related factors in order to increase our understanding of the pathogenesis of oropharyngeal candidiasis and fluconazole-refractory infections.

Prior to randomization to a long-term management strategy using fluconazole, patients are stratified into one of three groups according to their baseline CD4+ count (cells/mm3): 0-49, 50-100, and 101-150. Patients without oropharyngeal candidiasis (no thrush present) at enrollment and those patients who respond (no thrush present) to the initial acute therapy for an active infection are randomized 1: 1 to one of two management strategies for fluconazole: Arm A (episodic therapy) or Arm B (chronic suppressive therapy with continuous fluconazole). Patients are then followed for a duration of 24 months after enrollment of the last subject. Patients with active oropharyngeal candidiasis at time of enrollment will be treated with fluconazole for up to 2 weeks and patients who respond (no thrush present) are then randomized to a long-term management strategy. Those who do not respond (refractory disease) to the acute treatment are permanently discontinued from the study. Women in both groups will have the option of being treated for vulvovaginal candidiasis either through or outside the study.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

You may be eligible for this study if you:

- Are HIV-positive.

- Have a CD4+ cell count less than 150 cells/mm3.

- Had at least one episode of thrush in the 24 months before study entry.

- Have a life expectancy of at least 12 months.

- Weigh at least 88 pounds.

- Are 13 years of age or older (consent of parent or guardian required if under 18).

- Agree to practice abstinence or use effective methods of birth control during the

study.

Exclusion Criteria

You will not be eligible for this study if you:

- Have an allergy to azoles.

- Have had 3 episodes or more of thrush within 12 weeks of study entry.

- Have a history of esophageal candidiasis.

- Have a history of fluconazole-resistant infection.

- Have an active opportunistic infection requiring treatment within 14 days before study

entry.

- Have a fungal infection requiring certain medications.

- Have a severe liver disease (e. g., cirrhosis).

- Are unable to tolerate oral medications.

- Take certain medications.

- Are pregnant or breast-feeding.

Univ of Puerto Rico, San Juan 009365067, Puerto Rico

Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States

San Francisco Gen Hosp, San Francisco, California 941102859, United States

UCLA CARE Ctr, Los Angeles, California 90095, United States

Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Institute for Clinical Research, Washington, District of Columbia 20422, United States

Howard Univ, Washington, District of Columbia 20059, United States

Univ of Miami School of Medicine, Miami, Florida 331361013, United States

Emory Univ, Atlanta, Georgia 30308, United States

Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta, Georgia 303652225, United States

Queens Med Ctr, Honolulu, Hawaii 96816, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Northwestern Univ Med School, Chicago, Illinois 60611, United States

Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Louis A Weiss Memorial Hosp, Chicago, Illinois 60640, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States

Division of Inf Diseases/ Indiana Univ Hosp, Indianapolis, Indiana 46202, United States

Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States

Johns Hopkins Hosp, Baltimore, Maryland 21287, United States

State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States

Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States

Boston Med Ctr, Boston, Massachusetts 02118, United States

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States

Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States

St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States

Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr, New York, New York 10021, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Mount Sinai Med Ctr, New York, New York 10029, United States

Cornell Univ Med Ctr, New York, New York 10021, United States

Albert Einstein College of Medicine, Bronx, New York 10461, United States

SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States

Beth Israel Med Ctr, New York, New York 10003, United States

Saint Clare's Hosp and Health Ctr, New York, New York 10019, United States

St Mary's Hosp (Univ of Rochester/Infectious Diseases), Rochester, New York 14642, United States

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

Duke Univ Med Ctr, Durham, North Carolina 27710, United States

Case Western Reserve Univ, Cleveland, Ohio 44106, United States

Univ of Cincinnati, Cincinnati, Ohio 452670405, United States

Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States

MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States

Univ of Kentucky Lexington, Cincinnati, Ohio 45267, United States

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Philadelphia Veterans Administration Med Ctr, Philadelphia, Pennsylvania 19104, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville, Tennessee 37920, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Univ of Washington, Seattle, Washington 98104, United States

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Related publications:

Swindells S, Evans S, Zackin R, Goldman M, Haubrich R, Filler SG, Balfour HH Jr. Predictive value of HIV-1 viral load on risk for opportunistic infection. J Acquir Immune Defic Syndr. 2002 Jun 1;30(2):154-8.

Last updated: October 7, 2005