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Operational Research for Cryptococcal Antigen Screening (ORCAS)

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ClinicalTrials.gov Identifier: NCT01535469
Recruitment Status : Completed
First Posted : February 17, 2012
Last Update Posted : April 20, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
This will be a stepped wedge randomized trial design to evaluate the implementation of cryptococcal antigen (CRAG) screening and preemptive anti-fungal therapy of HIV-infected persons entering antiretroviral therapy (ART) outpatient treatment in Uganda. Those who are ART eligible with a CD4≤100 cells/mcL will have a serum/plasma CRAG performed by lateral flow assay. Those who are CRAG-positive and asymptomatic will be treated with high dose fluconazole. After 6 months survival with retention-in-care will be compared between those who are CRAG+ and CRAG negative

Condition or disease Intervention/treatment Phase
Cryptococcal Meningitis Cryptococcus Neoformans Cryptococcosis Drug: Fluconazole Phase 4

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3049 participants
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Operational Research for Cryptococcal Antigen Screening to Improve ART Survival
Actual Study Start Date : July 1, 2012
Primary Completion Date : June 2015
Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Fluconazole
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: CrAg Screening and Fluconazole
Cryptococcal Antigen (CrAg) Screening with preemptive antifungal treatment per World Health Organization (WHO) guidelines. Randomized Stepped Wedge design of phased implementation.
Drug: Fluconazole
Fluconazole 800mg orally daily for 2 weeks, then 400mg daily for 8 weeks
Other Name: Diflucan

Outcome Measures

Primary Outcome Measures :
  1. Retention in care [ Time Frame: 6-month ]
    1. before/after CRAG screening implementation (All persons)
    2. CRAG positive persons treated with high-dose fluconazole as compared to 6-month survival of CRAG negative persons who are eligible for antiretroviral therapy.

Secondary Outcome Measures :
  1. Cryptococcal meningitis-free survival time [ Time Frame: 6-month ]
    Cryptococcal meningitis-free survival time in those who are asymptomatic CRAG positive and treated with fluconazole compared to CRAG-negative persons with CD4<100 cells/mcL

  2. Survival Time [ Time Frame: 6-month ]
    Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.

  3. Uptake of CRAG screening and preemptive treatment [ Time Frame: baseline ]
  4. Time from CRAG+ test to receipt of fluconazole therapy [ Time Frame: Days from CD4 testing ]
  5. All-cause discontinuation of fluconazole [ Time Frame: 6-month ]
    Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)

  6. Percentage of participants with symptomatic cryptococcal meningitis [ Time Frame: baseline ]
  7. Risk factors for symptomatic cryptococcal meningitis [ Time Frame: baseline ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HIV-1 infection
  • CD4≤100 cells/mcL
  • Cryptococcal antigen (CRAG) positive
  • age >14 years

Exclusion Criteria:

  • Suspected Cryptococcal meningitis
  • Prior known history of cryptococcal meningitis
  • currently receiving HIV antiretroviral therapy
  • Allergy to any azole antifungal medication
  • Persons with known serious hepatic co-morbidities, transaminitis, or clinical jaundice who should not receive fluconazole in the opinion of the study investigator.
  • Current known pregnancy
Contacts and Locations

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): NCT01535469

Infectious Disease Institute, Makerere University
Kampala, Uganda
Kampala Capital Council Authority Clinics
Kampala, Uganda
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Infectious Diseases Institute, Uganda
Makerere University
Centers for Disease Control and Prevention
Principal Investigator: David B Meya, MMed Makerere University
Study Director: David R Boulware, MD MPH University of Minnesota - Clinical and Translational Science Institute
Study Director: Radha Rajasingham, MD Infectious Disease Institute
More Information

Additional Information:
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01535469     History of Changes
Other Study ID Numbers: U01GH000517 ( U.S. NIH Grant/Contract )
First Posted: February 17, 2012    Key Record Dates
Last Update Posted: April 20, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After publication, data to be shared upon request to the Infectious Disease Institute Research Department as per the institutional data sharing policy.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
cryptococcal meningitis
implementation science
stepped wedge design

Additional relevant MeSH terms:
Meningitis, Cryptococcal
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Central Nervous System Infections
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors