Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.
Journal article
Authors/Editors
Research Areas
No matching items found.
Publication Details
Author list: Jarvis JN, Leeme TB, Molefi M, Chofle AA, Bidwell G, Tsholo K, Tlhako N, Mawoko N, Patel RKK, Tenforde MW, Muthoga C, Bisson GP, Kidola J, Changalucha J, Lawrence D, Jaffar S, Hope W, Molloy SLF, Harrison TS
Publication year: 2019
Journal acronym: Clin Infect Dis
Volume number: 68
Issue number: 3
Start page: 393
End page: 401
Number of pages: 9
ISSN: 1058-4838
eISSN: 1537-6591
Languages: English-Great Britain (EN-GB)
Abstract
Background\nMethods\nResults\nConclusions\nClinical Trials Registration\nWe performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana.\nHuman immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day.\nEighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated.\nSingle-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial.\nISRCTN 10248064.
Keywords
No matching items found.
Documents
No matching items found.
