Operational Research for Cryptococcal Antigen Screening (ORCAS)

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ClinicalTrials.gov Identifier: NCT01535469

Recruitment Status : Completed

First Posted : February 17, 2012

Last Update Posted : April 20, 2017

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

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

Condition or disease	Intervention/treatment	Phase
Cryptococcal Meningitis Cryptococcus Neoformans Cryptococcosis	Drug: Fluconazole	Phase 4

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3049 participants
Intervention Model:	Single Group Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Operational Research for Cryptococcal Antigen Screening to Improve ART Survival
Actual Study Start Date :	July 1, 2012
Actual Primary Completion Date :	June 2015
Actual Study Completion Date :	June 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Fluconazole

Genetic and Rare Diseases Information Center resources: Cryptococcosis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

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 ]

Eligibility Criteria

Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:

Infectious Disease Institute This link exits the ClinicalTrials.gov site

Publications:

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. Review.

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.


Responsible Party:	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:	NCT01535469 History of Changes
Other Study ID Numbers:	U01GH000517 ( U.S. NIH Grant/Contract )
First Posted:	February 17, 2012 Key Record Dates
Last Update Posted:	April 20, 2017
Last Verified:	April 2017
Individual Participant Data (IPD) Sharing Statement:
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 Meningitis, Cryptococcal Cryptococcosis Central Nervous System Diseases Nervous System Diseases Meningitis, Fungal Central Nervous System Fungal Infections Mycoses 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

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