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Operational Research for Cryptococcal Antigen Screening (ORCAS)

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT01535469
First received: February 10, 2012
Last updated: April 19, 2017
Last verified: April 2017
  Purpose
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
Cryptococcosis
Drug: Fluconazole
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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 ]
    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 ]
    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 ]
    Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.

  • Uptake of CRAG screening and preemptive treatment [ Time Frame: baseline ]
  • Time from CRAG+ test to receipt of fluconazole therapy [ Time Frame: Days from CD4 testing ]
  • 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)

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

Enrollment: 3049
Actual Study Start Date: July 1, 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

  Eligibility

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

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535469

Locations
Uganda
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
Investigators
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:
Publications:
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01535469     History of Changes
Other Study ID Numbers: U01GH000517 ( US NIH Grant/Contract Award Number )
Study First Received: February 10, 2012
Last Updated: April 19, 2017
Individual Participant Data  
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
hiv
aids
implementation science
stepped wedge design
retention-in-care

Additional relevant MeSH terms:
Meningitis
Cryptococcosis
Meningitis, Cryptococcal
Central Nervous System Diseases
Nervous System Diseases
Mycoses
Meningitis, Fungal
Central Nervous System Fungal Infections
Central Nervous System Infections
Fluconazole
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

ClinicalTrials.gov processed this record on April 28, 2017