Nguyen Thi Thuy NganNhat Thanh Hoang LeNguyen Ngo Vi ViNinh Thi Thanh VanNguyen Thi Hoang MaiDuong Van AnhPhan Hai TrieuNguyen Phu Huong LanNguyen Hoan PhuNguyen van Vinh ChauDavid G. LallooWilliam HopeJustin BeardsleyNicholas J. WhiteRonald GeskusGuy E. ThwaitesDamian KrysanLuong Thi Hue TaiEvelyne KestelynTran Quang BinhLe Quoc HungNguyen Le Nhu TungJeremy N. DayFaculty of Tropical Medicine, Mahidol UniversityOxford University Clinical Research UnitCho Ray HospitalUniversity College London Hospitals NHS Foundation TrustLiverpool School of Tropical MedicineUniversity of LiverpoolFaculty of Medicine and HealthUniversity of Iowa Carver College of MedicineNuffield Department of MedicineThe Westmead Institute for Medical Research2022-08-042022-08-042021-09-01eLife. Vol.10, (2021)2050084X2-s2.0-85116894834https://repository.li.mahidol.ac.th/handle/123456789/76034Background: 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 https://clinicaltrials.gov/ct2/show/NCT03112031. 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyNeuroscienceArticleSCOPUS10.7554/eLife.68929