Amphotericin B for Non-HIV Cryptococcal Meningitis Patients
Status:
Enrolling by invitation
Trial end date:
2026-08-31
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 4
Details
Lead Sponsor:
Huashan Hospital
Treatments:
Amphotericin B Flucytosine Liposomal amphotericin B