학술논문
An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis
Document Type
article
Author
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; David G Lalloo; William Hope; Justin Beardsley; Nicholas J White; Ronald Geskus; Guy E Thwaites; Damian Krysan; Luong Thi Hue Tai; Evelyne Kestelyn; Tran Quang Binh; Le Quoc Hung; Nguyen Le Nhu Tung; Jeremy N Day
Source
eLife, Vol 10 (2021)
Subject
Language
English
ISSN
2050-084X
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: High-dose tamoxifen does not increase the clearance rate of Cryptococcus from CSF. Novel, affordable therapies are needed. Funding: 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.