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

Wellcome Open Research
Nguyen Thi Thuy NganJeremy N Day

Abstract

Background: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival. Tamoxifen, a selective estrogen receptor modulator used to treat breast cancer, has anti-cryptococcal activity, appearing synergistic when combined in vitro with amphotericin, and fungicidal when combined with fluconazole. It is concentrated in the brain and macrophages, off-patent, cheap and widely available. We designed a randomized trial to deliver initial efficacy and safety data for tamoxifen combined with amphotericin and fluconazole. Method: A phase II, open-label, randomized (1:1) controlled trial of tamoxifen (300mg/day) combined with amphoter...Continue Reading

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Citations

Apr 26, 2020·Current Opinion in Infectious Diseases·Kiran T Thakur
Feb 10, 2021·Nature Reviews. Microbiology·Kali R IyerLeah E Cowen

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Methods Mentioned

BETA
pregnancy test
contraception
RNAseq
nucleic acid amplification
blood drawn
blood draws
X-ray
biopsy

Clinical Trials Mentioned

NCT03112031

Software Mentioned

RNAseq
R
CliRes

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