| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.68929 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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