ORCAS: Operational Research for Cryptococcal Antigen Screening

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01535469
• Collaborator: Infectious Diseases Institute, Uganda (Other), Makerere University (Other), Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 3,049
• Locations: 2
• Arm: 1
• Actual Duration (Months): 35
• Patients Per Site: 1524.5
• Patients Per Site Per Month: 43.6

Study Details

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
• Actual Enrollment: 3049 participants
• Allocation: N/A
• 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: Jul 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

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 Names: Diflucan

Outcome Measures

Primary Outcome Measures

1. Retention in care [6-month]

   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

1. Cryptococcal meningitis-free survival time [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

2. Survival Time [6-month]

   Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.

3. Uptake of CRAG screening and preemptive treatment [baseline]

4. Time from CRAG+ test to receipt of fluconazole therapy [Days from CD4 testing]

5. All-cause discontinuation of fluconazole [6-month]

   Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)

6. Percentage of participants with symptomatic cryptococcal meningitis [baseline]

7. Risk factors for symptomatic cryptococcal meningitis [baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Infectious Disease Institute, Makerere University	Kampala		Uganda
2	Kampala Capital Council Authority Clinics	Kampala		Uganda

Sponsors and Collaborators

• University of Minnesota
• Infectious Diseases Institute, Uganda
• Makerere University
• Centers for Disease Control and Prevention

Investigators

• Principal Investigator: David B Meya, MMed, Makerere University
• Study Director: Radha Rajasingham, MD, Infectious Disease Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Infectious Disease Institute

Publications

• 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.
• 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.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01535469
• Other Study ID Numbers: HS1254; U01GH000517
• First Posted: Feb 17, 2012
• Last Update Posted: Jun 4, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: cryptococcal meningitis; hiv; aids; implementation science; stepped wedge design; retention-in-care
• Additional relevant MeSH terms: Meningitis, Cryptococcal; Cryptococcosis; Meningitis; Fluconazole

Study Results

No Results Posted as of Jun 4, 2020