AMBITION-CM
Trial question
Is single dose liposomal amphotericin B noninferior to WHO recommended treatment for cryptococcal meningitis?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
40.0% female
60.0% male
N = 814
814 patients (323 female, 491 male)
Inclusion criteria: HIV-positive adult patients with cryptococcal meningitis
Key exclusion criteria: receipt of > 2 doses of either amphotericin or fluconazole before screening; pregnancy or breastfeeding; receipt of contraindicated concomitant drugs; previous adverse reaction to a trial drug
Interventions
N=407 liposomal amphotericin B (a single high dose of liposomal amphotericin B at 10 mg/kg of body weight on day 1 plus 14 days of flucytosine at 100 mg/kg/day and fluconazole at 1200 mg/day)
N=407 WHO recommended treatment (amphotericin B deoxycholate at a dose of 1 mg/kg/day plus flucytosine at 100 mg/kg/day for 7 days, followed by fluconazole at 1200 mg/day for 7 days)
Primary outcome
Death from any cause at 10 weeks
24.8
28.7
28.7 %
21.5 %
14.3 %
7.2 %
0.0 %
Liposomal amphotericin B
World Health Organization recommended treatment
Difference not exceeding
nonferiority margin ✓
Difference not exceeding nonferiority margin in death from any cause at 10 weeks (24.8% vs. 28.7%; ARD -4.05, 95% CI -10.2 to 2.1)
Secondary outcomes
No significant difference in fungal clearance from CSF at day 14 (-0.4 log CFU/ml/day vs. -0.42 log CFU/ml/day; AD 0.017 log CFU/ml/day, 95% CI 0 to 0.04)
No significant difference in death from any cause at 4 weeks (17.2% vs. 18.7%; HR 0.92, 95% CI 0.66 to 1.27)
No significant difference in death from any cause at 16 weeks (28.3% vs. 29.2%; HR 0.95, 95% CI 0.73 to 1.22)
Safety outcomes
No significant differences in neutropenia, thrombocytopenia.
Significant difference in grade 3 or 4 adverse events (50.0% vs. 62.3%).
Conclusion
In HIV-positive adult patients with cryptococcal meningitis, liposomal amphotericin B was noninferior to WHO recommended treatment with respect to death from any cause at 10 weeks.
Reference
Joseph N Jarvis, David S Lawrence, David B Meya et al. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. N Engl J Med. 2022 Mar 24;386(12):1109-1120.
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