View clinical trials related to Cryptococcal Meningitis.
Filter by:Cryptococcal meningitis (CM) is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in Africa where the ongoing HIV/AIDS pandemic leads to higher prevalence of cryptococcosis. Combination of amphotericin and flucytosine (5-FC) is the mainstay of therapy for the initial management of CM. Indeed, it has even been shown that effective delivery of these therapies in Africa can lower mortality rates by 90%. This is a prospective open-label trial to compare the efficacy and safety of lower doses of 5FC during induction therapy to historical controls with standard 5FC dosing. Participants in the trial will receive 60mg/kg/day of 5-FC in 3 divided doses for 10 days. Single-dose liposomal amphotericin (10mg/kg) is preferred, if available. Amphotericin B 0.7-1.0 mg/kg/day may be used if needed. Historical controls drawn from the AMBITION trial will be used as a comparison group, selected weighted by inclusion/exclusion criteria, baseline characteristics and therapies received. Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mg/kg/day and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazole/day for 7 days. The intervention group received single- dose liposomal amphotericin plus 5-FC and fluconazole 1200 mg/day. All participants will receive fluconazole 1200mg/day during consolidation therapy from day 1 to 14 then 800mg/day from day 15 to 10 weeks, and 200mg/day after 10 weeks. All participants will receive lumbar punctures at diagnosis, day 3, day 5-7, day 10-14, and additionally as required for control of intracranial pressure and documentation of CSF sterilization. Controls from Ambition will be matched for the same LP windows. Therapeutic LPs conducted during the first week have a ~70% relative survival benefit.
Cryptococcus neoformans and C. gatti are important causes of central nervous system (CNS) infections with significant mortality, remaining a great public health challenge worldwide. Commonly seen as an opportunistic infection in adults with HIV/AIDS, cryptococcal meningitis (CM) accounts for 15% of HIV-related mortality globally [1]. In addition, a growing number of non-HIV CM patients have been observed in recent years with fatality approaching 30% in some areas [2,3]. It occurs in both those with natural or iatrogenic immunosuppression, as well as the apparently immunocompetent individuals. Approximately 65-70% of non-HIV CM patients were without any predisposing factors, particularly in the East Asia [4,5]. With the increasing number of hematopoietic stem cell transplantation, solid organ transplantation recipients and administration of immunosuppressive and corticosteroids agents, this illness will assume even greater public health significance. Current Infectious Disease Society of America (IDSA) guideline suggest the use of combination antifungal therapy: normal dose amphotericin (0.7-1mg/kg/day) combined with flucytosine for a minimum of 4 weeks, followed by fluconazole (600-800 mg/day) for a minimum of 10 weeks in total for HIV patients [6]. However, for non-HIV and immunocompetent patients, the treatment remains controversial. IDSA guideline recommended that the treatment of non-HIV patients could refer to the treatment of HIV patients. That is, amphotericin B combined with flucytosine is still administered in the induction period. However, as amphotericin B have nonspecific effect on ergosterol, it has strong side effects (hepatorenal toxicity, electrolyte disorder, anemia, ventricular fibrillation, etc.). Therefore, the dose of amphotericin B may not be appropriate for Asian patients due to the different drug metabolism and pharmacokinetic. In the prospective studies of Bennett[7] and Dismuke[8], low dose amphotericin B (0.3 mg/kg/d) combined with flucytosine achieved response rates of 66% and 85% at 6 weeks, respectively. A similar conclusion was also extracted from a large multicenter retrospective study that low dose amphotericin B (<0.7 mg/kg/d) combined with flucytosine for a minimum of 2 weeks, followed by fluconazole could achieve a response rate of 84%, indicating that the efficacy of low dose amphotericin B (< 0.7 mg/kg/d) may be equivalent with normal dose in non-HIV patients. Therefore, we plan to conduct a prospective, multicenter, open-label randomized controlled study to compare the efficacy and safety of normal dose amphotericin B (0.7 mg/kg/ d) and low dose amphotericin B (0.5 mg/kg/d) in the initial antifungal treatment for non-HIV cryptococcal meningitis patients.
In Mexico City, the main cause of mortality among people living with HIV (PLHIV) continues to be opportunistic infections (OIs). Early detection of OIs allows their timely treatment and improves their prognosis. The use of rapid diagnostic tests (RDT) based on antigens of the most frequent causative agents of OIs allows adequate screening of these patients and facilitates decision making at the point of care. Unfortunately, these studies are not widely available in the different PLHIV care centers in the CDMX. We will conduct an open-label, non-inferiority uncontrolled clinical trial to investigate the diagnostic performance of urinary lipoarabinomannan, urinary Histoplasma antigen and serum Cryptococcus antigen in patients presenting for care with advanced HIV in CDMX, supported by rapid cluster of differentiation 4 (CD4) testing with lateral flow technology. Four referral hospitals will participate over 12 months. All patients with diagnosed HIV disease and suspected advanced disease presenting for care at participating centers will be included in the study. An inventory of approximately 1000 RDT will be obtained and distributed among the participating sites. A study coordinator will be hired and will visit each site once a week to collect the study variables and follow up on the included patients. The primary outcome of the study will be the percentage of patients with advanced disease who present with diagnoses made by RDT compared to historical controls of patients diagnosed with OI in 2022 at participating centers by conventional methods. Secondary outcomes will be time to initiation of antiretroviral therapy (ART), time to initiation of OI treatment, and 30-day mortality after HIV diagnosis.
This pivotal, confirmatory trial seeks to independently verify the results observed in the EnACT Phase II Stage 2 trial (MB-70007).
To evaluate the efficacy and safety of ABCD in the treatment of cryptococcal meningitis in non-HIV patients at week 4, the end of induction therapy, week 10 and the end of consolidation therapy.
To study the clinical effectiveness and safety of amphotericin B with flucytosine-fluconazole therapy for cryptococcal meningitis in patients with HIV infection.
There has been no previous qualitative study conducted in a low-income setting which has aimed to explore the experience of individuals who enrol into a clinical trial for the management of a life-threatening illness. The investigators plan to collect data from trial participants, their next-of-kin, and researchers working on a multi-site randomised controlled trial for the treatment of HIV-associated cryptococcal meningitis.
Cryptococcal meningitis (CM) is one of the leading opportunistic infections and one of the most common causes of death in AIDS patients. Amphotericin B (AmB) is the corner stone in CM treatment. The effect of AmB was dose-dependent. Recent retrospective study indicated that longer duration rather than higher dose of AmB is necessary to reduce the mortality of CM. We aimed to explore the efficacy and safety of small dose but longer duration of AmB for the treatment of HIV-associated CM.
Three induction treatment strategies [ voriconazole +5FC vs. amphotericin deoxycholate (0.4-0.5 mg/kg/d)+5FC vs. amphotericin deoxycholate (0.7-1.0 mg/kg/d)+5FC ] for HIV-infected patients with cryptococcal meningitis were compared.
This study is designed as two sequential trials. The first is a phase I open label trial to evaluate the safety and tolerability of MAT2203. The maximal tolerated and non-toxic daily dose,will then be moved forward into a multi-day safety trial. The Phase II trial will investigate toxicity and early fungicidal activity (EFA) of MAT2203 with flucytosine.