Nguyen, Thi Thuy Ngan, Nhat, Thanh Hoang Le, Nguyen, Ngo Vi Vi, Ninh, Thi Thanh Van, Nguyen, Thi Hoang Mai, Duong, Van Anh, Phan, Hai Trieu, Nguyen, Phu Huong Lan, Nguyen, Hoan Phu, Nguyen, Van Vinh Chau et al (show 13 more authors)
(2021)
An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis.
ELIFE, 10.
e68929-.
Abstract
<h4>Background</h4>Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro. It is off-patent, cheap, and widely available. We performed a trial to determine its therapeutic potential.<h4>Methods</h4>Open label randomized controlled trial. Participants received standard care - amphotericin combined with fluconazole for the first 2 weeks - or standard care plus tamoxifen 300 mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration https://clinicaltrials.gov/ct2/show/NCT03112031.<h4>Results</h4>Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (-0.48log10 colony-forming units/mL/CSF control arm versus -0.49 tamoxifen arm, difference -0.005log10CFU/ml/day, 95% CI: -0.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation.<h4>Conclusions</h4>High-dose tamoxifen does not increase the clearance rate of <i>Cryptococcus</i> from CSF. Novel, affordable therapies are needed.<h4>Funding</h4>The trial was funded through the Wellcome Trust Asia Programme Vietnam Core Grant 106680 and a Wellcome Trust Intermediate Fellowship to JND grant number WT097147MA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Cryptococcus neoformans, Meningitis, Cryptococcal, Long QT Syndrome, Tamoxifen, Amphotericin B, Fluconazole, Antifungal Agents, Drug Therapy, Combination, Adult, Female, Male |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 Jan 2022 10:11 |
| Last Modified: | 30 Jan 2024 11:08 |
| DOI: | 10.7554/eLife.68929 |
| Open Access URL: | https://elifesciences.org/articles/68929 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147527 |
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