Operational Research for Cryptococcal Antigen Screening (ORCAS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborators:
Infectious Disease Research Institute
Makerere University
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01535469
First received: February 10, 2012
Last updated: June 30, 2014
Last verified: June 2014
  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: 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 ]

Estimated Enrollment: 3000
Study Start Date: July 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CrAg Screening
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
Genders Eligible for Study:   Both
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

Contacts
Contact: David B Meya, MBChB MMed +256772543730 david.meya@gmail.com
Contact: Elizabeth Nalintya, MBChB enalintya@yahoo.com

Locations
Uganda
Infectious Disease Institute, Makerere University Recruiting
Kampala, Uganda
Contact: David Meya, MMed    +256772543730    david.meya@gmail.com   
Contact: Andrew Kambugu, MMed    +256772507636    akambugu@idi.co.ug   
Principal Investigator: David Meya, MMed         
Sub-Investigator: Radha Rajasingham, MD         
Sub-Investigator: Yukari Manabe, MD         
Sub-Investigator: Andrew Kambugu, MMed         
Sub-Investigator: Elizabeth Nalintya, MBChB         
Kampala Capital Council Authority Clinics Recruiting
Kampala, Uganda
Principal Investigator: Elizabeth Nalintya, MBChB         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Infectious Disease Research Institute
Makerere University
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
Study First Received: February 10, 2012
Last Updated: June 30, 2014
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
hiv
aids
implementation science
stepped wedge design

Additional relevant MeSH terms:
Cryptococcosis
Meningitis
Meningitis, Cryptococcal
Mycoses
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Fluconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014