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An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis

Nguyen, Thi Thuy Ngan, Nhat, Thanh Hoang Le, Nguyen, Ngo Vi VI, Ninh, Thi Thanh Van, Thi Hoang, Mai, Duong, Van Anh, Phan, Hai Trieu, Nguyen, Phu Huong Lan, Nguyen, Hoan Phu, Nguyen, Van Vinh Chau, Lalloo, David ORCID:, Hope, William, Beardsley, Justin, White, Nicholas J, Geskus, Ronald, Thwaites, Guy E, Krysan, Damian, Thi Hue Tai, Luong, Kestelyn, Evelyne, Quang Binh, Tran, Hung, Le Quoc, Nguyen, Le Nhu Tung and Day, Jeremy N (2021) 'An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis'. eLife, Vol 2021, Issue 10, e68929.

elife-68929-v1 (1).pdf - Accepted Version
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Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anti-cancer 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 two weeks - or standard care plus tamoxifen 300mg/day. The primary end point was Early Fungicidal Activity (EFA) - the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration .

Results: 50 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.

Conclusion: 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.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 252 Antifungal agents. Antifungal antibiotics
WC Communicable Diseases > Mycoses > WC 475 Cryptococcosis. Sporotrichosis
WL Nervous System > WL 200 Meninges. Blood-brain barrier
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Debbie Jenkins
Date Deposited: 15 Oct 2021 08:48
Last Modified: 15 Oct 2021 08:48


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