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Safety Study of Fluconazole in Combination With Flucytosine for the Treatment of Early Cryptococcal Infection (SToP-Crypto)
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| First Received Date ICMJE | March 21, 2012 | |||||||||
| Last Updated Date | July 31, 2015 | |||||||||
| Start Date ICMJE | September 2013 | |||||||||
| Primary Completion Date | July 2014 (Final data collection date for primary outcome measure) | |||||||||
| Current Primary Outcome Measures ICMJE |
Survival at 12 Weeks [ Time Frame: 12 weeks ] | |||||||||
| Original Primary Outcome Measures ICMJE | Same as current | |||||||||
| Change History | Complete list of historical versions of study NCT01562132 on ClinicalTrials.gov Archive Site | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Outcome Measures ICMJE | Not Provided | |||||||||
| Original Other Outcome Measures ICMJE | Not Provided | |||||||||
| Descriptive Information | ||||||||||
| Brief Title ICMJE | Safety Study of Fluconazole in Combination With Flucytosine for the Treatment of Early Cryptococcal Infection | |||||||||
| Official Title ICMJE | An Open Label Randomized Controlled Phase IIb Trial to Determine the Safety of Oral Fluconazole in Combination With Flucytosine as Compared to Fluconazole Alone | |||||||||
| Brief Summary | The purpose of this study is to determine if treatment with two medicines in combination (fluconazole and flucytosine) is safe as compared with one medicine alone (fluconazole) for the treatment of an early infection with a fungus called cryptococcus. | |||||||||
| Detailed Description | Currently there is wide variation in practice and little evidence to guide the treatment of early cryptococcal infection in HIV-infected individuals with advanced immunosuppression. However, epidemiologic studies suggest that this may be a promising novel approach to decrease the mortality due to cryptococcal meningitis (CM), the second leading cause of death among HIV-infected individuals in many resource-limited settings. Screening asymptomatic HIV-infected individuals with advanced immunosuppression for serum cryptococcal antigen (CrAg) clearly identifies a population at high risk of CM and death and is a feasible screening method for resource-limited settings. However, screening with serum CrAg alone without additional diagnostic studies identifies a heterogeneous clinical population with early cryptococcal infection, many of whom already have sub-clinical meningeal infection or fungemia. The mainstay of anti-cryptococcal therapy in resource-limited settings is oral fluconazole though preliminary evidence suggests this is not an effective treatment. Thus, there is a critical need for potent therapies that (1) can be safely administered in resource-limited settings and (2) are effective in a heterogeneous population of HIV-infected individuals with advanced immunosuppression and early cryptococcal infection who are initiating anti-retroviral therapy (ART). This single center, open-label, randomized Phase IIb study is being conducted to assess the safety and estimate the efficacy of oral fluconazole in combination with flucytosine for the treatment of early cryptococcal infection. The study will be based at two sites supported by Family AIDS Care and Education Services (FACES) in Western Kenya. A consecutive sample of 100 HIV-infected adults with CD4 cell count ≤100 cells/µl and serum CrAg titer ≥1:2 who have no signs or symptoms of severe, systemic cryptococcal infection will be enrolled. At enrollment, specimens from participants will be cultured for evidence of Cryptococcus neoformans. Individuals who meet inclusion and exclusion criteria and consent to participate in the study will be randomized to combination therapy with oral fluconazole (1200mg/day) plus flucytosine (100mg/kg/day) or fluconazole alone for the fourteen days of therapy. Subsequently both groups will receive anti-retroviral therapy as well as fluconazole 800mg/day for 8 weeks followed by 200mg/day. The primary safety endpoint will be the incidence of treatment-related adverse events and serious adverse events. The primary efficacy endpoint will be survival at 12 weeks. In addition, we will offer additional diagnostic testing and aim for 50% participation, approximately 25 individuals from each arm. We will perform a battery of diagnostic tests including chest radiography, fungal cultures in blood, sputum, urine, stool and cerebrospinal fluid (CSF), cryptococcal antigen testing in the CSF, and gram stain, Ziehls-Nielsen stain and India Ink staining of CSF sediment. Anti-fungal susceptibility testing via broth microdilution and polymerase chain reaction serotyping and mating type analysis will be performed on clinical isolates. |
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| Study Type ICMJE | Interventional | |||||||||
| Study Phase | Phase 2 | |||||||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
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| Condition ICMJE | Cryptococcal Infection Disseminated | |||||||||
| Intervention ICMJE |
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| Publications * | Not Provided | |||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | ||||||||||
| Recruitment Status ICMJE | Terminated | |||||||||
| Enrollment ICMJE | 6 | |||||||||
| Completion Date | July 2014 | |||||||||
| Primary Completion Date | July 2014 (Final data collection date for primary outcome measure) | |||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Ages | 18 Years and older (Adult, Senior) | |||||||||
| Accepts Healthy Volunteers | No | |||||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||||||||
| Listed Location Countries ICMJE | Kenya | |||||||||
| Removed Location Countries | ||||||||||
| Administrative Information | ||||||||||
| NCT Number ICMJE | NCT01562132 | |||||||||
| Other Study ID Numbers ICMJE | R21NS077858-01( U.S. NIH Grant/Contract ) R21NS077858-01 ( U.S. NIH Grant/Contract ) |
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| Has Data Monitoring Committee | Yes | |||||||||
| U.S. FDA-regulated Product | Not Provided | |||||||||
| IPD Sharing Statement | Not Provided | |||||||||
| Responsible Party | Ana-Claire Meyer, Yale University | |||||||||
| Study Sponsor ICMJE | Yale University | |||||||||
| Collaborators ICMJE |
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| Investigators ICMJE |
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| PRS Account | Yale University | |||||||||
| Verification Date | July 2015 | |||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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