CandidiasisPhase 3NCT00000676
Randomized Comparative Study of Fluconazole Versus Clotrimazole Troches in the Prevention of Serious Fungal Infection in Patients With AIDS or Advanced AIDS-Related Complex. (A Nested Study of ACTG 081)
A Phase 3 study testing Clotrimazole and Fluconazole in people with Candidiasis and Mycoses, run by National Institute of Allergy and Infectious Diseases (NIAID) at 26 sites in 2 countries.
Trial summary
To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Candidiasis, Mycoses, HIV Infections
- What is being tested?
- Clotrimazole and Fluconazole
- How many people
- 500 participants
- Where
- 26 sitesin 2 countries
- Study dates
- Start not givento Nov 1993
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Required:
- Zidovudine (AZT).
- Antipneumocystis prophylaxis.
- Allowed:
- Topical suppressive antifungal agents.
Show all 18Show fewer
- Eligibility requirements are:
- Participation in NIAID ACTG 081.
- No history of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis.
- Willingness to sign an informed consent.
- Transaminases < 5 x upper limit of normal.
- Noncompliance will not be a reason for withdrawal of a patient from the study, unless patient refuses further treatment.
- Allowed:
- A history of oropharyngeal, vaginal or cutaneous candidiasis.
- Dermatophyte infections (i.e., tinea pedis) at entry but not active candida infection. Sites of suspected dermatophyte involvement other than the feet should have candida excluded by culture.
- Prior Medication:
- Allowed:
- Topical suppressive antifungal agents.
Who cannot join
- Co-existing Condition:
- Patients with the following conditions or diseases are excluded:
- History of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis.
- Active systemic fungal infection at time of enrollment.
- Active superficial fungal infection at time of entry. (Such patients may be treated with topical antifungal agents and may be randomized if they are in clinical remission 14 days after completion of such therapy.)
- Concurrent Medication:
Show all 17Show fewer
- Excluded:
- Amphotericin B.
- Fluconazole.
- Itraconazole.
- SCH 39304.
- Other systemic antifungals.
- Patients with the following are excluded:
- Previous or currently active systemic fungal infection.
- History of allergy or intolerance to imidazole or azoles.
- Positive serum cryptococcal antigen titer at any dilution.
- Requiring multi-agent therapy for tuberculosis or for symptomatic Mycobacterium avium infection.
Trial locations and contacts
26 sites in 2 countries.
26 sites in 2 countries
United States25 sites
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287
Bmc Actg Crs
Boston, Massachusetts, 02118
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, 02215
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215
Unc Aids Crs
Chapel Hill, North Carolina
Northwestern University CRS
Chicago, Illinois
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois
Univ. of Cincinnati CRS
Cincinnati, Ohio
Case CRS
Cleveland, Ohio, 44106
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 43210
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202
Univ. of Miami AIDS CRS
Miami, Florida, 33136
University of Minnesota, ACTU
Minneapolis, Minnesota, 55455
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York
Stanford CRS
Palo Alto, California
Pitt CRS
Pittsburgh, Pennsylvania, 15213
Univ. of Rochester ACTG CRS
Rochester, New York
Ucsd, Avrc Crs
San Diego, California, 92093
Ucsf Aids Crs
San Francisco, California
University of Washington AIDS CRS
Seattle, Washington, 98122
Washington U CRS
St Louis, Missouri
About this study
To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Primarily, to compare the rates of invasive infections by C. neoformans, endemic mycoses, and Candida. To compare the mortality rates due to fungal infections between two antifungal prophylactic treatments. Secondarily, to assess the effect of prophylaxis on the incidence of severe fungal infections, defined as invasive infections and esophageal candidiasis and less severe mucocutaneous infection.
Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
Read the detailed description
Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
AMENDED: 11/01/90 Sufficient numbers of patients will be enrolled from all centers starting at week 8 of participation in the parent study to achieve a total of 240 evaluable patients who will remain in the nested study for a maximum duration of 45 months. Enrollment will continue until all eligible and interested 081 patients are enrolled. Fungal prophylaxis will begin at the time of enrollment into the nested study and will continue until an efficacy or safety end point is reached, until withdrawal from the nested study, or until death.
Original design: Patients included are those already enrolled in ACTG 081. Patients are enrolled from all centers at either week 8, 12, 16, 20, 24, 28, or 32 of participation in the parent study. They are randomized to receive either oral fluconazole or clotrimazole troches. Prophylaxis continues until a serious fungal infection develops, the end of the parent study is reached (which is expected to be December 1991), the patient withdraws from either the nested or parent study, or the patient dies. Clinical examination is performed at 2 weeks and then monthly (or more if clinically indicated) for the duration of antifungal prophylaxis; the schedule of evaluation is the same as for the parent study. There is a 1-month postprophylaxis follow-up after discontinuation of prophylaxis for any reason.
- Conditions
- Candidiasis, Mycoses, HIV Infections
- Being tested
- Clotrimazole, Fluconazole
- Keywords
- Mycoses, Fluconazole, Clotrimazole, Antifungal Agents, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
- Medical subject headings
- Candidiasis, Mycoses, HIV Infections, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClotrimazoleDrug
FluconazoleDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionNov 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for CandidiasisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Enrolment
- 500 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Bozzettee S, Study chairPowderly WG, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000676
- Sponsor's protocol ID
- ACTG 981
- Other IDs
- 11504
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 2 Nov 2021
- Results posted
- No
Publications
Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring:8-9.
PubMed 11362451Hanna L. Treatment for HIV-related fungal infections. BETA. 1995 Jun:10-7.
PubMed 11362539Powderly WG. Fungal infections. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:274
Powderly WG. Prophylaxis of fungal infection in HIV infection. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:270
Powderly WG, Finkelstein D, Feinberg J, Frame P, He W, van der Horst C, Koletar SL, Eyster ME, Carey J, Waskin H, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995 Mar 16;332(11):700-5. doi: 10.1056/NEJM199503163321102.
PubMed 7854376
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Comparative Study of Fluconazole Versus Clotrimazole Troches in the Prevention of Serious Fungal Infection in Patients With AIDS or Advanced AIDS-Related Complex. (A Nested Study of ACTG 081)
- ClinicalTrials.gov ID
- NCT00000676
- Acronym / sponsor ID
- ACTG 981
- Conditions
- Candidiasis, Mycoses, HIV Infections
- Keywords
- Mycoses, Fluconazole, Clotrimazole, Antifungal Agents, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Pfizer
- Study completion
- Nov 1993 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Primarily, to compare the rates of invasive infections by C. neoformans, endemic mycoses, and Candida. To compare the mortality rates due to fungal infections between two antifungal prophylactic treatments. Secondarily, to assess the effect of prophylaxis on the incidence of severe fungal infections, defined as invasive infections and esophageal candidiasis and less severe mucocutaneous infection.
Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
Detailed description
Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
AMENDED: 11/01/90 Sufficient numbers of patients will be enrolled from all centers starting at week 8 of participation in the parent study to achieve a total of 240 evaluable patients who will remain in the nested study for a maximum duration of 45 months. Enrollment will continue until all eligible and interested 081 patients are enrolled. Fungal prophylaxis will begin at the time of enrollment into the nested study and will continue until an efficacy or safety end point is reached, until withdrawal from the nested study, or until death.
Original design: Patients included are those already enrolled in ACTG 081. Patients are enrolled from all centers at either week 8, 12, 16, 20, 24, 28, or 32 of participation in the parent study. They are randomized to receive either oral fluconazole or clotrimazole troches. Prophylaxis continues until a serious fungal infection develops, the end of the parent study is reached (which is expected to be December 1991), the patient withdraws from either the nested or parent study, or the patient dies. Clinical examination is performed at 2 weeks and then monthly (or more if clinically indicated) for the duration of antifungal prophylaxis; the schedule of evaluation is the same as for the parent study. There is a 1-month postprophylaxis follow-up after discontinuation of prophylaxis for any reason.
Study design
- Primary purpose
- Prevention
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Zidovudine (AZT).
- Antipneumocystis prophylaxis.
- Topical suppressive antifungal agents.
- Participation in NIAID ACTG 081.
- No history of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis.
Key exclusion criteria (17 listed)
- History of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis.
- Active systemic fungal infection at time of enrollment.
- Active superficial fungal infection at time of entry. (Such patients may be treated with topical antifungal agents and may be randomized if they are in clinical remission 14 days after completion of such therapy.)
- Amphotericin B.
- Fluconazole.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clotrimazole | Drug | – |
| Fluconazole | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Background: PubMed 11362451Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring:8-9.
- Background: PubMed 11362539Hanna L. Treatment for HIV-related fungal infections. BETA. 1995 Jun:10-7.
- BackgroundPowderly WG. Fungal infections. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:274
- BackgroundPowderly WG. Prophylaxis of fungal infection in HIV infection. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:270
- Background: PubMed 7854376Powderly WG, Finkelstein D, Feinberg J, Frame P, He W, van der Horst C, Koletar SL, Eyster ME, Carey J, Waskin H, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995 Mar 16;332(11):700-5. doi: 10.1056/NEJM199503163321102.
Related trials for Candidiasis
RecruitingPhase 2
Evaluate the Efficacy and Safety of Ruxolitinib on Hair Regrowth in Patients With Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)-Associated Alopecia Areata
Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (Apeced), Alopecia Areata
RecruitingObservational study
Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
Chronic Mucocutaneous Candidiasis, Invasive Aspergillosis
RecruitingObservational study
Middle East Study of Infections in Patients With Hematological Malignancies
Hematological Malignancy, Hematopoetic Stem Cell Transplantation
Recruiting
Comparison of Uncomplicated Candidemia Therapy Duration in Children and Adults
Invasive Candidiasis
RecruitingPhase 3
A Phase 3 Efficacy and Safety Study of Fosmanogepix for the Treatment of Adult Participants With Candidemia and/or Invasive Candidiasis.
Candidemia, Candidiasis, Invasive
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bozzettee S study chair
Powderly WG study chair
26 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Clotrimazole and Fluconazole in people with Candidiasis and Mycoses, run by National Institute of Allergy and Infectious Diseases (NIAID) at 26 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000676, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.