Cryptococcal Antigen Screening Plus Sertraline (C-ASSERT)

University of Minnesota (UMN)

Status and phase: Terminated; Phase 3

Conditions: Cryptococcal Infections; AIDS-Related Opportunistic Infections; Cryptococcosis

Treatments: Drug: Fluconazole; Drug: Sertraline; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03002012

U01AI125003 (U.S. NIH Grant/Contract)

33238 (Other Identifier)

Details and patient eligibility

About

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.

Full 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+).

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

22 participants in 2 patient groups, including a placebo group

Sertraline

Experimental group

Description:

Fluconazole Standard of Care + Sertraline

Treatment:

Drug: Sertraline

Drug: Fluconazole

Control

Placebo Comparator group

Description:

Fluconazole Standard of Care + Placebo Oral Tablet

Treatment:

Drug: Placebo Oral Tablet

Drug: Fluconazole