Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial



Jarvis, Joseph N, Leeme, Tshepo B, Molefi, Mooketsi, Chofle, Awilly A, Bidwell, Gabriella, Tsholo, Katlego, Tlhako, Nametso, Mawoko, Norah, Patel, Raju KK, Tenforde, Mark W
et al (show 9 more authors) (2019) Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial. CLINICAL INFECTIOUS DISEASES, 68 (3). pp. 393-401.

[img] Text
e00885-18.full.pdf - Published version

Download (1MB)

Abstract

<h4>Background</h4>We 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.<h4>Methods</h4>Human 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.<h4>Results</h4>Eighty 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.<h4>Conclusions</h4>Single-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.<h4>Clinical trials registration</h4>ISRCTN 10248064.

Item Type: Article
Uncontrolled Keywords: cryptococcal meningitis, HIV, AmBisome, amphotericin, randomized clinical trial
Depositing User: Symplectic Admin
Date Deposited: 11 Sep 2018 06:41
Last Modified: 19 Jan 2023 01:18
DOI: 10.1093/cid/ciy515
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3026072