An interventional study of Fluconazole and Fixed dose - Stavudine, lamivudine and Nevirapine in Cryptococcal Meningitis and HIV Infections, sponsored by University of Zimbabwe. Completed at 1 site in Zimbabwe. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-07-18.
Sponsored by University of Zimbabwe · Not applicable, Interventional, and Treatment
Cryptococcal Meningitis continues to be one of the most devastating AIDS defining illness in sub-Saharan Africa. Despite the availability of azoles such as fluconazole for treatment, mortality remains high with some studies showing 100% mortality. The investigators designed a study to determine if timing of the initiation of antiretroviral therapy (ART) in patients with cryptococcal meningitis and HIV would improve survival. The investigators hypothesis was that early initiation of ART result in improved mortality for patients with HIV and cryptococcal meningitis.
Cryptococcosis is an invasive fungal infection caused by an encapsulated yeast. Cryptococcosis in humans is almost always caused by Cryptococcus neoformans. The advent of the HIV epidemic has lead to a profound increase in the number of reported cases of cryptococcal meningoencephalitis throughout the world, particularly in sub-Saharan Africa. In Zimbabwe an analysis of the case reports at one of the major tertiary care hospitals showed an increase in the admission rate from meningitis between 1985-1995 from 78 to 523 cases per 100000 admissions with an increase in the number of those cases due to cryptococcosis from 5% to 46.2%.
Cryptococcosis typically develops at a CD4 count of less than 50 cells/ mm3, and is the initial AIDS defining illness in up to 50-60% of patients.
Prior to the introduction of amphotericin B, flucytosine and azoles, mortality from C neoformans meningoencephalitis was close to 100%. The introduction of amphotericin B led to a significant decrease in mortality with 60-70% of patients being successfully treated. The introduction of fluconazole prophylaxis in the 1990s lead to a significant decrease in the incidence of cryptococcosis. The use of antiretroviral therapy has also caused a significant decrease in the incidence of cryptococcal meningitis.
Due to the prohibitive cost of amphotericin B and flucytosine, in many developing countries such as Zimbabwe, the mainstay of the treatment of CM is fluconazole. The current standard treatment is with fluconazole 400mg/day for 8-10 weeks, may be too low to result in adequate CNS concentration of the drug to achieve adequate killing of C. neoformans. Clinically some physicians in Zimbabwe have noted that patients are not responding adequately to this regimen and have started to treat patients with higher doses of fluconazole. Previous studies have shown that higher doses of fluconazole can be used for the treatment of CM and are well tolerated. In our proposed study, patients will be treated with high dose oral fluconazole at 800mg/day for a total 10 week period.
The advent of the increased access to ART in sub-Saharan Africa provides an additional opportunity to improve morbidity and mortality in all AIDS patients. There are as yet no definitive studies to indicate if there is an advantage to immediate ART therapy in the setting of acute CM compared to deferring therapy after the first 10 weeks of intensive CM therapy. This study is designed to address this question and provide physicians in sub-Saharan Africa with evidence based guidelines for the appropriate management of HIV positive patients with acute presentation of CM.
54 studies on the registry are indexed under Meningitis, Cryptococcal; 6 are open to participants now.
This study's enrollment of 54 is below the median of 143 across 35 interventional studies indexed under Meningitis, Cryptococcal.
Browse Meningitis, Cryptococcal studies →University of Zimbabwe is the lead sponsor of 18 studies on the registry; 2 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Early initiation of antiretroviral therapy. Patients in this treatment group were started on Fluconazole 800mg by mouth every day for Cryptococcal Meningitis, and within 72hrs of diagnosis were started on First line antiretroviral therapy per Zimbabwe treatment guidelines which is Stavudine, Lamivudine and Nevirapine.
Drug: Fluconazole · Drug: Fixed dose - Stavudine, lamivudine and Nevirapine
Delayed initiation of antiretroviral therapy. Patients in this treatment group were started on Fluconazole 800mg by mouth every day for Cryptococcal Meningitis, and after completion of high dose fluconazole for 10 weeks, the patients in this group were started on First line antiretroviral therapy per Zimbabwe treatment guidelines which is Stavudine, Lamivudine and Nevirapine.
Drug: Fluconazole · Drug: Fixed dose - Stavudine, Lamivudine, Nevirapine
Fluconazole 800mg po qday
Initiation within 72 hours of diagnosis of Cryptococcal meningitis.
Delayed initiation of ART defined as 10 weeks after initiation of high dose fluconazole therapy.
Mortality
Time frame: 2 years
The record gives a start of Oct 2006, a primary completion of Oct 2008 and a completion of Oct 2009. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.
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University of Zimbabwe