Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cryptococcal Antigen Screening Plus Sertraline (C-ASSERT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03002012
Recruitment Status : Terminated (SAEs with n=1 serotonin syndrome, n=2 SAEs after sertraline interruption.)
First Posted : December 23, 2016
Results First Posted : December 26, 2019
Last Update Posted : June 9, 2020
Sponsor:
Collaborators:
Infectious Diseases Institute, Uganda
National Institute of Allergy and Infectious Diseases (NIAID)
Mbarara University of Science and Technology
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Cryptococcosis Cryptococcal Infections AIDS-Related Opportunistic Infections Drug: Sertraline Drug: Placebo Oral Tablet Drug: Fluconazole Phase 3

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+).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cryptococcal Antigen Screening Plus Sertraline
Actual Study Start Date : November 15, 2017
Actual Primary Completion Date : March 13, 2018
Actual Study Completion Date : March 13, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Meningitis

Arm Intervention/treatment
Experimental: Sertraline
Fluconazole Standard of Care + Sertraline
Drug: Sertraline
sertraline 400mg/day
Other Names:
  • Zoloft
  • Lustral
  • Sertraline hydrochloride

Drug: Fluconazole
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

Placebo Comparator: Control
Fluconazole Standard of Care + Placebo Oral Tablet
Drug: Placebo Oral Tablet
matched placebo tablet
Other Name: Placebo

Drug: Fluconazole
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




Primary Outcome Measures :
  1. 6 Month Meningitis-free Survival [ Time Frame: 6 months ]

    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


Secondary Outcome Measures :
  1. 6-month Survival [ Time Frame: 6 months ]
    Survival through 6 months

  2. Cumulative Incidence of Symptomatic Cryptococcal Meningoencephalitis [ Time Frame: 6 months ]
    Cumulative incidence of symptomatic cryptococcal meningoencephalitis through 6 months

  3. Number of Clinical Adverse Events (Grade 3-5) [ Time Frame: 6 months ]
    Number of Clinical Adverse Events by Division of AIDS (DAIDS) Scale for Grade 3-5 events through 6 months

  4. Number of Laboratory Grade 3-5 Adverse Events [ Time Frame: 6 months ]
    Number of Laboratory Grade 3-5 Adverse Events through 6 months as per the Division of AIDS (DAIDS) grading scale

  5. All-Cause Premature Study Drug/Placebo Discontinuation [ Time Frame: 6 months ]
    Number of participants whose study drug/placebo use was halted prematurely due to any cause through 6 months

  6. Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time [ Time Frame: 12 weeks ]
    Prevalence of depression by Patient Health Questionnaire (PHQ-9) over 6 months as measured at baseline, 4 weeks, 8 weeks, and 12 weeks. The PHQ-9 is a 9-item instrument for screening, diagnosing, monitoring, and measuring the severity of depression. Items are rated on a scale from 0 (not at all) to 3 (nearly every day). Total score is a sum of 9 item scores (Range 0-27). Greater scores indicate greater depressive symptoms. PHQ-9 scores of: 0-4 Minimal/No depression; 5-9 Mild depression; 10-14 Moderate depression; 15-19 Moderate severe depression; 20-27 Severe depression. This endpoint reports the median (interquartile range) of the PHQ-9 scores over time.


Other Outcome Measures:
  1. Adherence to Study Drug [ Time Frame: 12 weeks ]
    Participants' percent adherence to study drug regiment by pharmacy medication counts, representing the percent of the total prescribed medication taken by participants.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03002012


Locations
Layout table for location information
Uganda
Infectious Disease Institute, Makerere University
Kampala, Uganda, 22418
Sponsors and Collaborators
University of Minnesota
Infectious Diseases Institute, Uganda
National Institute of Allergy and Infectious Diseases (NIAID)
Mbarara University of Science and Technology
Investigators
Layout table for investigator information
Study Director: Elizabeth K Nalintya, MBChB MPH Infectious Disease Institute
Study Director: Radha Rajasingham, MD University of Minnesota
  Study Documents (Full-Text)

Documents provided by University of Minnesota:
Study Protocol  [PDF] October 10, 2017
Statistical Analysis Plan  [PDF] September 6, 2017

Additional Information:
Publications of Results:
Layout table for additonal information
Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT03002012    
Other Study ID Numbers: U01AI125003 ( U.S. NIH Grant/Contract )
U01AI125003 ( U.S. NIH Grant/Contract )
33238 ( Other Identifier: DAIDS-ES ID )
First Posted: December 23, 2016    Key Record Dates
Results First Posted: December 26, 2019
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: A formal written data sharing plan exists. Protocol and trial documents can be shared. De-identified data can be shared after trial completion.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Available for at least 5 years
Access Criteria: Upon request to the Principal Investigator

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Minnesota:
cryptococcal antigen
preemptive treatment
CRAG+
sertraline
fluconazole
randomized clinical trial
HIV
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Opportunistic Infections
AIDS-Related Opportunistic Infections
Cryptococcosis
Virus Diseases
Parasitic Diseases
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Mycoses
Fluconazole
Sertraline
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors