Operational Research for Cryptococcal Antigen Screening (ORCAS)

This study is currently recruiting participants.
Verified August 2013 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: August 21, 2013
Last verified: August 2013
  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: December 2014
Estimated Primary Completion Date: December 2014 (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
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: August 21, 2013
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 April 16, 2014