6/28/23, 12:08 AM AMBITION-CM Pathway Feedback Search Clinical Topics Home Studies AMBITION CM AMBITION CM Disease Disease Cryptococcal meningitis Human immunodeficiency virus i 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 N = 814 60.0% male 814 patients (323 female, 491 male) Inclusion criteria: human immunodeficiency virus positive adults with cryptococcal meningitis Key exclusion criteria: receipt of > 2 doses of either amphotericin or fluconazole before screening; pregnancy or breast-feeding; 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) https://web.pathway.md/studies/rec3hh7085z7GqpRj 1/2 6/28/23, 12:08 AM AMBITION-CM Pathway 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 28.7 % 28.7 24.8 21.5 % 14.3 % Difference not exceeding nonferiority margin 7.2 % 0.0 % Liposomal amphotericin B World Health Organization recommended treatment 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 human immunodeficiency virus positive adults 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. Open reference URL https://web.pathway.md/studies/rec3hh7085z7GqpRj 2/2