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Operational Research for Cryptococcal Antigen Screening (ORCAS)

Primary Purpose

Cryptococcal Meningitis, Cryptococcus Neoformans, Cryptococcosis

Status
Completed
Phase
Phase 4
Locations
Uganda
Study Type
Interventional
Intervention
Fluconazole
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cryptococcal Meningitis focused on measuring cryptococcal meningitis, hiv, aids, implementation science, stepped wedge design, retention-in-care

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Infectious Disease Institute, Makerere University
  • Kampala Capital Council Authority Clinics

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CrAg Screening and Fluconazole

Arm Description

Cryptococcal Antigen (CrAg) Screening with preemptive antifungal treatment per World Health Organization (WHO) guidelines. Randomized Stepped Wedge design of phased implementation.

Outcomes

Primary Outcome Measures

Retention in care
before/after CRAG screening implementation (All persons) 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
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
Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.
Uptake of CRAG screening and preemptive treatment
Time from CRAG+ test to receipt of fluconazole therapy
All-cause discontinuation of fluconazole
Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)
Percentage of participants with symptomatic cryptococcal meningitis
Risk factors for symptomatic cryptococcal meningitis

Full Information

First Posted
February 10, 2012
Last Updated
June 2, 2020
Sponsor
University of Minnesota
Collaborators
Infectious Diseases Institute, Uganda, Makerere University, Centers for Disease Control and Prevention
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1. Study Identification

Unique Protocol Identification Number
NCT01535469
Brief Title
Operational Research for Cryptococcal Antigen Screening
Acronym
ORCAS
Official Title
Operational Research for Cryptococcal Antigen Screening to Improve ART Survival
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
July 1, 2012 (Actual)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
Infectious Diseases Institute, Uganda, Makerere University, Centers for Disease Control and Prevention

4. Oversight

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
Data Monitoring Committee
Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptococcal Meningitis, Cryptococcus Neoformans, Cryptococcosis
Keywords
cryptococcal meningitis, hiv, aids, implementation science, stepped wedge design, retention-in-care

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
Outcomes Assessor
Allocation
N/A
Enrollment
3049 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CrAg Screening and Fluconazole
Arm Type
Experimental
Arm Description
Cryptococcal Antigen (CrAg) Screening with preemptive antifungal treatment per World Health Organization (WHO) guidelines. Randomized Stepped Wedge design of phased implementation.
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Other Intervention Name(s)
Diflucan
Intervention Description
Fluconazole 800mg orally daily for 2 weeks, then 400mg daily for 8 weeks
Primary Outcome Measure Information:
Title
Retention in care
Description
before/after CRAG screening implementation (All persons) CRAG positive persons treated with high-dose fluconazole as compared to 6-month survival of CRAG negative persons who are eligible for antiretroviral therapy.
Time Frame
6-month
Secondary Outcome Measure Information:
Title
Cryptococcal meningitis-free survival time
Description
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
Time Frame
6-month
Title
Survival Time
Description
Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.
Time Frame
6-month
Title
Uptake of CRAG screening and preemptive treatment
Time Frame
baseline
Title
Time from CRAG+ test to receipt of fluconazole therapy
Time Frame
Days from CD4 testing
Title
All-cause discontinuation of fluconazole
Description
Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)
Time Frame
6-month
Title
Percentage of participants with symptomatic cryptococcal meningitis
Time Frame
baseline
Title
Risk factors for symptomatic cryptococcal meningitis
Time Frame
baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David B Meya, MMed
Organizational Affiliation
Makerere University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Radha Rajasingham, MD
Organizational Affiliation
Infectious Disease Institute
Official's Role
Study Director
Facility Information:
Facility Name
Infectious Disease Institute, Makerere University
City
Kampala
Country
Uganda
Facility Name
Kampala Capital Council Authority Clinics
City
Kampala
Country
Uganda

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
After publication, data to be shared upon request to the Infectious Disease Institute Research Department as per the institutional data sharing policy.
IPD Sharing Time Frame
Upon request
IPD Sharing Access Criteria
Upon request
Citations:
PubMed Identifier
22410867
Citation
Rajasingham R, Meya DB, Boulware DR. Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):e85-91. doi: 10.1097/QAI.0b013e31824c837e.
Results Reference
background
PubMed Identifier
20597693
Citation
Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010 Aug 15;51(4):448-55. doi: 10.1086/655143.
Results Reference
background
PubMed Identifier
30399034
Citation
Meya DB, Kiragga AN, Nalintya E, Morawski BM, Rajasingham R, Park BJ, Mubiru A, Kaplan JE, Manabe YC, Boulware DR. Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/microL: A Stepped-Wedge, Cluster-Randomized Trial. J Acquir Immune Defic Syndr. 2019 Feb 1;80(2):182-189. doi: 10.1097/QAI.0000000000001894.
Results Reference
result
Links:
URL
http://www.idi-makerere.com
Description
Infectious Disease Institute

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Operational Research for Cryptococcal Antigen Screening

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