Treatment With Tamoxifen in Cryptococcal Meningitis

• Status: Completed
• Trial end date: 2018-07-17
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to develop initial efficacy, feasibility, and safety data regarding the use of Tamoxifen in combination with amphotericin B and fluconazole in the treatment of cryptococcal meningitis. The results of the study will inform the design and feasibility of a larger study powered to a survival endpoint. The study hypothesis is that adding tamoxifen to standard antifungal therapy increases the rate of clearance of yeast from cerebrospinal fluid. Increased rates of clearance of yeast from cerebrospinal fluid have previously been associated with improved clinical outcomes, including survival and disability.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: Cho Ray Hospital; Cho Ray Hospital, Ho Chi Minh City, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Liverpool School of Tropical Medicine; University of Liverpool; University of Rochester
• Treatments: Amphotericin B; Antifungal Agents; Fluconazole; Liposomal amphotericin B; Miconazole; Tamoxifen

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