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Operational Research for Cryptococcal Antigen Screening (ORCAS)

This study has been completed.
Infectious Diseases Institute, Uganda
Makerere University
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute Identifier:
First received: February 10, 2012
Last updated: July 28, 2015
Last verified: July 2015
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 Intervention Phase
Cryptococcal Meningitis
Cryptococcus Neoformans
Drug: Fluconazole
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Operational Research for Cryptococcal Antigen Screening to Improve ART Survival

Resource links provided by NLM:

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Retention in care [ Time Frame: 6-month ] [ Designated as safety issue: Yes ]
    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:
  • Cryptococcal meningitis-free survival time [ Time Frame: 6-month ] [ Designated as safety issue: Yes ]
    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

  • Survival Time [ Time Frame: 6-month ] [ Designated as safety issue: Yes ]
    Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.

  • Uptake of CRAG screening and preemptive treatment [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Time from CRAG+ test to receipt of fluconazole therapy [ Time Frame: Days from CD4 testing ] [ Designated as safety issue: No ]
  • All-cause discontinuation of fluconazole [ Time Frame: 6-month ] [ Designated as safety issue: Yes ]
    Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)

  • Percentage of participants with symptomatic cryptococcal meningitis [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Risk factors for symptomatic cryptococcal meningitis [ Time Frame: baseline ] [ Designated as safety issue: No ]

Enrollment: 3049
Study Start Date: July 2012
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Ages Eligible for Study:   14 Years and older   (Child, Adult, Senior)
Genders 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
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Please refer to this study by its identifier: 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 Identifier: NCT01535469     History of Changes
Other Study ID Numbers: U01GH000517 
Study First Received: February 10, 2012
Last Updated: July 28, 2015
Health Authority: Uganda: National Council for Science and Technology
Uganda: Research Ethics Committee
Uganda: National Drug Authority
United States: Institutional Review Board

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 processed this record on January 18, 2017