{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T03:01:42Z","timestamp":1775790102730,"version":"3.50.1"},"reference-count":38,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Wellcome Trust Asia Programme Vietnam Core Grant 106680"],"award-info":[{"award-number":["Wellcome Trust Asia Programme Vietnam Core Grant 106680"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Intermediate Fellowship WT097147MA"],"award-info":[{"award-number":["Intermediate Fellowship WT097147MA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Open label randomized controlled trial. Participants received standard care \u2013 amphotericin combined with fluconazole for the first 2 weeks \u2013 or standard care plus tamoxifen 300 mg\/day. The primary end point was Early Fungicidal Activity (EFA) \u2013 the rate of yeast clearance from cerebrospinal fluid (CSF). Trial registration\n                      <jats:ext-link ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03112031\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03112031<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Fifty patients were enrolled (median age 34 years, 35 male). Tamoxifen had no effect on EFA (\u22120.48log10 colony-forming units\/mL\/CSF control arm versus \u22120.49 tamoxifen arm, difference \u22120.005log10CFU\/ml\/day, 95% CI: \u22120.16, 0.15, p=0.95). Tamoxifen caused QTc prolongation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      High-dose tamoxifen does not increase the clearance rate of\n                      <jats:italic>Cryptococcus<\/jats:italic>\n                      from CSF. Novel, affordable therapies are needed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.68929","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T08:01:51Z","timestamp":1632816111000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68929","source":"Crossref","is-referenced-by-count":33,"title":["An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis"],"prefix":"10.7554","volume":"10","author":[{"given":"Nguyen Thi Thuy","family":"Ngan","sequence":"first","affiliation":[{"name":"Department of Tropical 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for Tropical Diseases, Ho Chi Minh City, Viet Nam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G","family":"Lalloo","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Infectious Disease Research, Institute of Translational Medicine, Liverpool University, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Beardsley","sequence":"additional","affiliation":[{"name":"The University of Sydney, Marie Bashir Institute, NSW, Camperdown, Australia"},{"name":"Westmead Institute for Medical Research, Westmead, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-1978","authenticated-orcid":true,"given":"Nicholas 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