Cryptococcal Antigen Screening Plus Sertraline

Cryptococcal Antigen Screening Plus Sertraline

Sponsors

Lead Sponsor: University of Minnesota

Collaborator: Infectious Diseases Institute, Uganda
National Institute of Allergy and Infectious Diseases (NIAID)
Mbarara University of Science and Technology

Source University of Minnesota
Brief Summary

Cryptococcal meningitis or "Crypto" is a life threatening fungal infection around the brain that requires hospitalization for treatment for 14 days and then continued therapy. Crypto causes 15-20% of HIV/AIDS-related deaths worldwide. However, this infection can be detected before one develops symptoms and becomes ill. People can be screened for infection by a blood test to detect "cryptococcal antigen," (called CrAg), which is part of the fungus, in blood. The World Health Organization and over 22 countries worldwide recommend CrAg screening of all persons with advanced AIDS entering or re-entering into HIV care.

However, it is not known how best to treat people with cryptococcal antigen in their blood, who don't otherwise yet have symptoms of infection around their brain. If no treatment is given, almost all people will develop infection of the brain and/or die. International guidelines suggest using both HIV medicines and an anti-fungal medicine, called fluconazole, to treat this early infection. However, despite this treatment approximately 1 in 4 people may get sick and/or die.

Researchers have recently discovered another medicine that may work against the Cryptococcus fungus. This medicine is called Sertraline, and it is actually a medicine that has been used for more than 25 years to treat depression (sadness). Sertraline is one of the most commonly used medicines worldwide.

The purpose of this research clinical trial is to determine if standard fluconazole antifungal therapy plus a high dose of Sertraline, will be better than standard fluconazole therapy alone for treating early disseminated cryptococcal infection in persons who are asymptomatic and do not yet have infection of the brain (i.e. meningitis).

This study seeks to test if Sertraline will improve survival through 6-months. Prior studies have shown that >90% of those who survive 6-months will survive >5 years.

Detailed Description

This is a double-blind, randomized placebo-controlled clinical trial testing sertraline as an antifungal medicine in combination with fluconazole for treatment of HIV-infected persons with AIDS and asymptomatic cryptococcal antigenemia (CrAg+).

Overall Status Terminated
Start Date November 15, 2017
Completion Date March 13, 2018
Primary Completion Date March 13, 2018
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
6 Month Meningitis-free Survival 6 months
Secondary Outcome
Measure Time Frame
6-month Survival 6 months
Cumulative Incidence of Symptomatic Cryptococcal Meningoencephalitis 6 months
Number of Clinical Adverse Events (Grade 3-5) 6 months
Number of Laboratory Grade 3-5 Adverse Events 6 months
All-Cause Premature Study Drug/Placebo Discontinuation 6 months
Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time 12 weeks
Enrollment 22
Condition
Intervention

Intervention Type: Drug

Intervention Name: Sertraline

Description: sertraline 400mg/day

Arm Group Label: Sertraline

Intervention Type: Drug

Intervention Name: Placebo Oral Tablet

Description: matched placebo tablet

Arm Group Label: Control

Other Name: Placebo

Intervention Type: Drug

Intervention Name: Fluconazole

Description: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).

Other Name: Fluconazole 200mg tab

Eligibility

Criteria:

Inclusion Criteria:

- HIV-infected

- Cryptococcal antigen (CrAg) positive in blood

- Age >=18 years

- Written informed consent

- Women of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use one reliable method of contraception while receiving fluconazole >=400mg/day

Exclusion Criteria:

- Prior history of cryptococcal meningitis

- Suspected meningitis or mania

- Suspected/known cirrhosis, jaundice, or alanine aminotransferase (ALT) >5x upper limit of normal

- Receiving an antidepressant medicine

- Receiving antifungal therapy, >1 week

- Pregnant or Breastfeeding

- Contraindication to sertraline or fluconazole

- Current rifampin use or other prohibited medication

- Electrocardiogram corrected QT interval (QTc) >450ms

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Location
Facility: Infectious Disease Institute, Makerere University
Location Countries

Uganda

Verification Date

June 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Sertraline

Type: Experimental

Description: Fluconazole Standard of Care + Sertraline

Label: Control

Type: Placebo Comparator

Description: Fluconazole Standard of Care + Placebo Oral Tablet

Acronym C-ASSERT
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov