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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000951

Collaborator

Washington University School of Medicine (Other)

948

Enrollment

Locations

17.6

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Candidiasis, Oral HIV Infections	Drug: Fluconazole	Phase 4

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.

Study Design

Study Type:

Interventional

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

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

Actual Study Completion Date :

May 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
2	UCLA CARE Ctr	Los Angeles	California	United States	90095
3	Univ of California / San Diego Treatment Ctr	San Diego	California	United States	921036325
4	San Francisco Gen Hosp	San Francisco	California	United States	941102859
5	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
6	Howard Univ	Washington	District of Columbia	United States	20059
7	Institute for Clinical Research	Washington	District of Columbia	United States	20422
8	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
9	Emory Univ	Atlanta	Georgia	United States	30308
10	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia	United States	303652225
11	Queens Med Ctr	Honolulu	Hawaii	United States	96816
12	Univ of Hawaii	Honolulu	Hawaii	United States	96816
13	Northwestern Univ Med School	Chicago	Illinois	United States	60611
14	Cook County Hosp	Chicago	Illinois	United States	60612
15	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
16	Louis A Weiss Memorial Hosp	Chicago	Illinois	United States	60640
17	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
18	Division of Inf Diseases/ Indiana Univ Hosp	Indianapolis	Indiana	United States	46202
19	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana	United States	46202
20	Univ of Iowa Hosp and Clinic	Iowa City	Iowa	United States	52242
21	State of MD Div of Corrections / Johns Hopkins Univ Hosp	Baltimore	Maryland	United States	212052196
22	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
23	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts	United States	02114
24	Boston Med Ctr	Boston	Massachusetts	United States	02118
25	Hennepin County Med Clinic	Minneapolis	Minnesota	United States	55415
26	Univ of Minnesota	Minneapolis	Minnesota	United States	55455
27	St Paul Ramsey Med Ctr	Saint Paul	Minnesota	United States	55101
28	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri	United States	63112
29	Univ of Nebraska Med Ctr	Omaha	Nebraska	United States	681985130
30	Albert Einstein College of Medicine	Bronx	New York	United States	10461
31	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
32	Beth Israel Med Ctr	New York	New York	United States	10003
33	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
34	Saint Clare's Hosp and Health Ctr	New York	New York	United States	10019
35	Cornell Univ Med Ctr	New York	New York	United States	10021
36	Mem Sloan - Kettering Cancer Ctr	New York	New York	United States	10021
37	St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr	New York	New York	United States	10021
38	Mount Sinai Med Ctr	New York	New York	United States	10029
39	St Mary's Hosp (Univ of Rochester/Infectious Diseases)	Rochester	New York	United States	14642
40	Univ of Rochester Medical Center	Rochester	New York	United States	14642
41	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
42	Duke Univ Med Ctr	Durham	North Carolina	United States	27710
43	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
44	Univ of Kentucky Lexington	Cincinnati	Ohio	United States	45267
45	Case Western Reserve Univ	Cleveland	Ohio	United States	44106
46	MetroHealth Med Ctr	Cleveland	Ohio	United States	441091998
47	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
48	Philadelphia Veterans Administration Med Ctr	Philadelphia	Pennsylvania	United States	19104
49	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania	United States	19104
50	Julio Arroyo	West Columbia	South Carolina	United States	29169
51	Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr	Knoxville	Tennessee	United States	37920
52	Univ of Texas Galveston	Galveston	Texas	United States	775550435
53	Univ of Washington	Seattle	Washington	United States	98104
54	Univ of Puerto Rico	San Juan		Puerto Rico	009365067