Journal article
An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis
eLife, Vol.10, e68929
09/28/2021
DOI: 10.7554/eLife.68929
PMCID: PMC8547950
PMID: 34581270
Abstract
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.
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.
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.
High-dose tamoxifen does not increase the clearance rate of
from CSF. Novel, affordable therapies are needed.
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.
Details
- Title: Subtitle
- An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis
- Creators
- Nguyen Thi Thuy Ngan - Cho Ray HospitalNhat Thanh Hoang Le - Oxford University Clinical Research UnitNguyen Ngo Vi Vi - Oxford University Clinical Research UnitNinh Thi Thanh Van - Oxford University Clinical Research UnitNguyen Thi Hoang Mai - Oxford University Clinical Research UnitDuong Van Anh - Oxford University Clinical Research UnitPhan Hai Trieu - Oxford University Clinical Research UnitNguyen Phu Huong Lan - Hospital for Tropical DiseasesNguyen Hoan Phu - Oxford University Clinical Research UnitNguyen Van Vinh Chau - The Hospital for Tropical Diseases, Ho Chi Minh City, Viet NamDavid G Lalloo - Liverpool School of Tropical MedicineWilliam Hope - University of LiverpoolJustin Beardsley - The University of SydneyNicholas J White - Mahidol Oxford Tropical Medicine Research UnitRonald Geskus - Oxford University Clinical Research UnitGuy E Thwaites - Oxford University Clinical Research UnitDamian Krysan - University of IowaLuong Thi Hue Tai - Hospital for Tropical DiseasesEvelyne Kestelyn - Oxford University Clinical Research UnitTran Quang Binh - Cho Ray HospitalLe Quoc Hung - Cho Ray HospitalNguyen Le Nhu Tung - The Hospital for Tropical Diseases, Ho Chi Minh City, Viet NamJeremy N Day - Oxford University Clinical Research Unit
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.10, e68929
- DOI
- 10.7554/eLife.68929
- PMID
- 34581270
- PMCID
- PMC8547950
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Grant note
- 106680 / Wellcome Trust WT097147MA / Wellcome Trust Wellcome Trust
- Language
- English
- Date published
- 09/28/2021
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984297436402771
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