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CryptococcosisPhase 3C-ASSERTNCT03002012

Cryptococcal Antigen Screening Plus Sertraline

A Phase 3 study testing Sertraline and Fluconazole in people with Cryptococcosis and Cryptococcal Infections, run by University of Minnesota at 1 site in Uganda.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sertraline and Fluconazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
22 participants
Where
1 siteUganda
Study dates
15 Nov 2017to 13 Mar 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • Contraindication to sertraline or fluconazole
  • Current rifampin use or other prohibited medication
  • Electrocardiogram corrected QT interval (QTc) >450ms

Trial locations and contacts

1 site in 1 country.

Uganda1 site

  • Infectious Disease Institute, Makerere University

    Kampala, 22418

Other trials in Uganda

About this study

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.

Read more

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.

Read the 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+).

Being tested
Sertraline, Placebo Oral Tablet, Fluconazole
Keywords
cryptococcal antigen, preemptive treatment, CRAG+, sertraline, fluconazole, randomized clinical trial, HIV
Medical subject headings
Cryptococcosis, AIDS-Related Opportunistic Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SertralineDrug

    Also called Zoloft, Lustral, Sertraline hydrochloride

    sertraline 400mg/day

  • Placebo Oral TabletDrug

    Also called Placebo

    matched placebo tablet

  • FluconazoleDrug

    Also called Fluconazole 200mg tab

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

Study groups in NCT03002012
Study groupRoleWhat they receive
SertralineExperimentalFluconazole Standard of Care + Sertraline
Receives: Drug: Sertraline; Drug: Fluconazole
ControlPlacebo comparatorFluconazole Standard of Care + Placebo Oral Tablet
Receives: Drug: Placebo Oral Tablet; Drug: Fluconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6 Month Meningitis-free Survival

    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

    Measured: 6 months

Secondary outcomes (6)

  1. 6-month Survival

    Survival through 6 months

    Measured: 6 months

  2. Cumulative Incidence of Symptomatic Cryptococcal Meningoencephalitis

    Cumulative incidence of symptomatic cryptococcal meningoencephalitis through 6 months

    Measured: 6 months

  3. Number of Clinical Adverse Events (Grade 3-5)

    Number of Clinical Adverse Events by Division of AIDS (DAIDS) Scale for Grade 3-5 events through 6 months

    Measured: 6 months

  4. Number of Laboratory Grade 3-5 Adverse Events

    Number of Laboratory Grade 3-5 Adverse Events through 6 months as per the Division of AIDS (DAIDS) grading scale

    Measured: 6 months

  5. All-Cause Premature Study Drug/Placebo Discontinuation

    Number of participants whose study drug/placebo use was halted prematurely due to any cause through 6 months

    Measured: 6 months

  6. Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time

    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.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2016 (estimated)
  2. Study start15 Nov 2017
  3. Primary completion13 Mar 2018
  4. Study completion13 Mar 2018

Why it stopped: SAEs with n=1 serotonin syndrome, n=2 SAEs after sertraline interruption.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03002012
Sponsor's protocol ID
U01AI125003
Other IDs
U01AI125003, 33238
Acronym
C-ASSERT
Status last verified
Jun 2020
First submitted
14 Dec 2016
Last updated
9 Jun 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: A formal written data sharing plan exists. Protocol and trial documents can be shared. De-identified data can be shared after trial completion.

Publications

  • Boulware DR, Nalintya E, Rajasingham R, Kirumira P, Naluyima R, Turya F, Namanda S, Rutakingirwa MK, Skipper CP, Nikweri Y, Hullsiek KH, Bangdiwala AS, Meya DB. Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial. Med Mycol. 2020 Nov 10;58(8):1037-1043. doi: 10.1093/mmy/myaa033.

    PubMed 32415846

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sertraline and Fluconazole in people with Cryptococcosis and Cryptococcal Infections, run by University of Minnesota at 1 site in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6 Month Meningitis-free Survival (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03002012, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.

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