Clinical Trial: Cryptococcal Antigen Screening Plus Sertraline

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Cryptococcal Antigen Screening Plus Sertraline

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).

Cryptococcal meningitis free survival with retention-in-care through 6 months

  • Those who die of any cause are failures
  • Those developing symptomatic cryptococcal meningitis are failures
  • Those lost to follow up and unable to be tracked are considered failures


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 6-month survival time [ Time Frame: 6 months ]
    Survival time through 6 months
  • Cumulative incidence of symptomatic cryptococcal meningoencephalitis [ Time Frame: 6 months ]
    Cumulative incidence of symptomatic cryptococcal meningoencephalitis through 6 months
  • Incidence of Clinical Adverse Events (Grade 3-5) [ Time Frame: 6 months ]
    Incidence of Clinical Adverse Events by Division of AIDS (DAIDS) Scale for Grade 3-5 events through 6 months
  • Incidence of Laboratory Grade 3-5 Adverse Events [ Time Frame: 6 months ]
    Incidence of Laboratory Grade 3-5 Adverse Events through 6 months as per the Division of AIDS (DAIDS) grading scale
  • Cumulative incidence of all-cause premature study drug/placebo discontinuation [ Time Frame: 6 months ]
    Cumulative incidence of all-cause premature study drug/placebo discontinuation through 6 months
  • Prevalence of depression by Patient Health Questionnaire (PHQ-9) over time [ Time Frame: 6 months ]
    Prevalence of depression by Patient Health Questionnaire (PHQ-9) over 6 months as measured at baseline, 4 weeks, 8 weeks, and 12 weeks


Original Secondary Outcome:

  • 6-month survival time [ Time Frame: 6 months ]
  • Cumulative incidence of symptomatic cryptococcal meningoencephalitis [ Time Frame: 6 months ]
  • Incidence of Clinical Adverse Events (Grade 3-5) [ Time Frame: 6 months ]
  • Incidence of Laboratory Grade 3-5 Adverse Events [ Time Frame: 6 months ]
  • Cumulative incidence of all-cause premature study drug/placebo discontinuation [ Time Frame: 6 months ]
  • Prevalence of depression by Patient Health Questionnaire (PHQ-9) over time [ Time Frame: 6 months ]


Information By: University of Minnesota - Clinical and Translational Science Institute

Dates:
Date Received: December 14, 2016
Date Started: June 30, 2017
Date Completion: October 2021
Last Updated: May 9, 2017
Last Verified: May 2017