Back to Search
Start Over
Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.
- Source :
-
The New England journal of medicine [N Engl J Med] 2022 Mar 24; Vol. 386 (12), pp. 1109-1120. - Publication Year :
- 2022
-
Abstract
- Background: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known.<br />Methods: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin.<br />Results: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log <subscript>10</subscript> colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log <subscript>10</subscript> CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%).<br />Conclusions: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).<br /> (Copyright © 2022 Massachusetts Medical Society.)
- Subjects :
- AIDS-Related Opportunistic Infections mortality
Administration, Oral
Africa South of the Sahara
Amphotericin B adverse effects
Antifungal Agents adverse effects
Drug Administration Schedule
Drug Therapy, Combination
Fluconazole adverse effects
Flucytosine adverse effects
HIV Infections complications
Meningitis, Cryptococcal mortality
AIDS-Related Opportunistic Infections drug therapy
Amphotericin B administration & dosage
Antifungal Agents administration & dosage
Fluconazole administration & dosage
Flucytosine administration & dosage
Meningitis, Cryptococcal drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 386
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 35320642
- Full Text :
- https://doi.org/10.1056/NEJMoa2111904