Cryptococcal Antigen Screening Plus Sertraline
Condition: Cryptococcosis; Cryptococcal Infections; AIDS-Related Opportunistic Infections
MeSH terms: Infections; Communicable Diseases; Opportunistic Infections; AIDS-Related Opportunistic Infections; Cryptococcosis
Intervention: Sertraline; Placebo Oral Tablet; Fluconazole
Intervention description: sertraline 400mg/day; matched placebo tablet; Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months).
Intervention MeSH terms: Fluconazole; Sertraline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cryptococcal antigen; preemptive treatment; CRAG+; sertraline; fluconazole; randomized clinical trial; HIV

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.
    

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