Treatment With Tamoxifen in Cryptococcal Meningitis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03112031
• Date of registration: 29/03/2017
• Prospective Registration: Yes
• Primary sponsor: Oxford University Clinical Research Unit, Vietnam
• Public title: Treatment With Tamoxifen in Cryptococcal Meningitis
• Scientific title: A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis
• Date of first enrolment: October 10, 2017
• Target sample size: 50
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03112031
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United Kingdom, United States, Vietnam

Contacts

• Name: Jeremy Day, MD
• Affiliation: Oxford University Clinical Research Unit

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age = 18 years

- Cryptococcal meningitis (CM) defined as a syndrome consistent with CM and one or more
of:

- positive CSF India ink (budding encapsulated yeasts),

- C. neoformans cultured from CSF or blood,

- positive cryptococcal antigen Lateral Flow Antigen Test (LFA) in CSF

- Informed consent to participate given by patient or acceptable representative

- Known HIV infection status, or patient agrees to HIV testing on this admission

Exclusion Criteria:

- Pregnancy or breast-feeding

- History of thromboembolic disease such as pulmonary embolism or deep venous thrombosis

- On anti-coagulant medication

- On medication known to prolong the QT interval other than fluconazole, such as
fluoroquinolones or antidepressants.

- Known cardiac conduction defect including long QT syndromes

- QTc at baseline > 500ms

- Currently receiving treatment for cryptococcal meningitis and having received > 4 days
of anti-cryptococcal meningitis therapy

- Known allergy to Tamoxifen

- Currently or history of receiving treatment with Tamoxifen for breast cancer or other
indication

- Current or history of uterine cancer including endometrial cancer and uterine sarcoma

- Renal failure (defined as creatinine >3*ULN (upper limit of normal), despite adequate
hydration)

- Failure to consent - the patient, or if they are incapacitated, their responsible
relative, declines to enter the study

- Allergy to amphotericin B or fluconazole



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Meningitis Streptococcal

Hiv

Meningitis

Meningoencephalitis

Intervention(s)

Drug: Tamoxifen

Drug: Amphotericin B

Drug: Fluconazole

Primary Outcome(s)

Early Fungicidal Activity (EFA), i.e. the rate of clearance of yeast from cerebrospinal fluid [Time Frame: over the first 2 weeks following randomisation]

Secondary Outcome(s)

Longitudinal measurements of intracranial pressure during the first 2 weeks [Time Frame: during the first 2 weeks]

Time to new neurological event or death until 10 weeks [Time Frame: until 10 weeks]

Blood and CSF concentrations of amphotericin, Tamoxifen and fluconazole [Time Frame: During hospital stay, an average of 10 weeks]

Adverse events [Time Frame: During hospital stay, an average of 10 weeks]

CD4 count at 10 weeks [Time Frame: at 10 weeks]

QT prolongation [Time Frame: During hospital stay, an average of 10 weeks]

Survival until 10 weeks after randomization [Time Frame: 10 weeks after randomisation]

Disability at 10 weeks [Time Frame: at 10 weeks]

Rate of IRIS until 10 weeks (in HIV infected patients only) [Time Frame: until 10 weeks]

Rate of Cryptococcal meningitis relapse [Time Frame: until 10 weeks]

Visual deficit at 10 weeks [Time Frame: at 10 weeks]

Secondary ID(s)

28CN

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Liverpool School of Tropical Medicine

University of Liverpool

Cho Ray Hospital

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

University of Rochester