Clinical trial NCT00000951: A Study to Compare the Use of Fluconazole as Continuous Therapy Versus Periodic Therapy in HIV-Positive Patients With Recurrent Thrush
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Candidiasis, Oral
HIV Infections
Keywords: AIDS-Related Opportunistic Infections
Fluconazole
Antifungal Agents
Candidiasis, Oral
Drug Administration Schedule
Pharyngeal Diseases
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Washington University School of Medicine
First posted: 2001-08-31
Enrollment: 948
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Washington
country: United States
facility: Howard Univ
state: District of Columbia
city: Washington
country: United States
facility: Institute for Clinical Research
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory Univ
state: Georgia
city: Atlanta
country: United States
facility: Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
state: Georgia
city: Honolulu
country: United States
facility: Queens Med Ctr
state: Hawaii
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: Louis A Weiss Memorial Hosp
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Division of Inf Diseases/ Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Iowa City
country: United States
facility: Univ of Iowa Hosp and Clinic
state: Iowa
city: Baltimore
country: United States
facility: State of MD Div of Corrections / Johns Hopkins Univ Hosp
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Boston
country: United States
facility: Boston Med Ctr
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Med Clinic
state: Minnesota
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: St Paul Ramsey Med Ctr
state: Minnesota
city: Saint Louis
country: United States
facility: St Louis Regional Hosp / St Louis Regional Med Ctr
state: Missouri
city: Omaha
country: United States
facility: Univ of Nebraska Med Ctr
state: Nebraska
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Saint Clare's Hosp and Health Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mem Sloan - Kettering Cancer Ctr
state: New York
city: New York
country: United States
facility: St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Rochester
country: United States
facility: St Mary's Hosp (Univ of Rochester/Infectious Diseases)
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Univ of Kentucky Lexington
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia Veterans Administration Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Knoxville
country: United States
facility: Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
state: Tennessee
city: Galveston
country: United States
facility: Univ of Texas Galveston
state: Texas
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
name: Mitchell Goldman
role: STUDY_CHAIR
name: Scott G. Filler
role: STUDY_CHAIR
References:
citation: Swindells S, Evans S, Zackin R, Goldman M, Haubrich R, Filler SG, Balfour HH Jr; AIDS Clinical Trial Group 722 Study Team. Predictive value of HIV-1 viral load on risk for opportunistic infection. J Acquir Immune Defic Syndr. 2002 Jun 1;30(2):154-8. doi: 10.1097/00042560-200206010-00003.