Operational Research for Cryptococcal Antigen Screening

Cryptococcal Meningitis Clinical Trial

— ORCAS  

Official title:

Operational Research for Cryptococcal Antigen Screening to Improve ART Survival

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01535469
• Other study ID #: HS1254
• Secondary ID: U01GH000517
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2012
• Est. completion date: June 2015

Study information

• Verified date: June 2020
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3049
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• Cryptococcosis
• Cryptococcus Neoformans
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• Fluconazole
Fluconazole 800mg orally daily for 2 weeks, then 400mg daily for 8 weeks

Locations

Country	Name	City	State
Uganda	Infectious Disease Institute, Makerere University	Kampala
Uganda	Kampala Capital Council Authority Clinics	Kampala

Sponsors (4)

Lead Sponsor	Collaborator
University of Minnesota	Centers for Disease Control and Prevention, Infectious Diseases Institute, Uganda, Makerere University

Country where clinical trial is conducted

Uganda, 

References & Publications (3)

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 In — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6-month
Secondary	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	6-month
Secondary	Survival Time	Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.	6-month
Secondary	Uptake of CRAG screening and preemptive treatment		baseline
Secondary	Time from CRAG+ test to receipt of fluconazole therapy		Days from CD4 testing
Secondary	All-cause discontinuation of fluconazole	Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)	6-month
Secondary	Percentage of participants with symptomatic cryptococcal meningitis		baseline
Secondary	Risk factors for symptomatic cryptococcal meningitis		baseline

External Links

•   Infectious Disease Institute