Operational Research for Cryptococcal Antigen Screening

Phase 4

Completed

• Conditions: Cryptococcal Meningitis; Cryptococcus Neoformans; Cryptococcosis
• Interventions: Drug: Fluconazole

• Registration Number: NCT01535469
• Lead Sponsor: University of Minnesota

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-02-10
• Study First Submitted QC: 2012-02-16
• Study First Posted: 2012-02-17
• Study Start: 2012-07-01
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-02
• Last Update Posted: 2020-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3049

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Retention in care	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

Name	Time	Method
All-cause discontinuation of fluconazole	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	baseline
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
Survival Time	6-month	Survival time among CRAG+ vs. CRAG negative persons with CD4\<100 cells/mcL.
Uptake of CRAG screening and preemptive treatment	baseline
Time from CRAG+ test to receipt of fluconazole therapy	Days from CD4 testing
Risk factors for symptomatic cryptococcal meningitis	baseline

Trial Locations

Locations (2)

Infectious Disease Institute, Makerere University; 🇺🇬 Kampala, Uganda

Kampala Capital Council Authority Clinics; 🇺🇬 Kampala, Uganda