Clinical trial NCT01535469: Operational Research for Cryptococcal Antigen Screening
Official title: Operational Research for Cryptococcal Antigen Screening to Improve ART Survival
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cryptococcal Meningitis
Cryptococcus Neoformans
Cryptococcosis
Keywords: cryptococcal meningitis
hiv
aids
implementation science
stepped wedge design
retention-in-care
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Infectious Diseases Institute, Uganda
name: Makerere University
name: Centers for Disease Control and Prevention
First posted: 2012-02-17
Enrollment: 3049
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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


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

Primary outcomes:
measure: Retention in care
timeFrame: 6-month
Secondary outcomes:
measure: Cryptococcal meningitis-free survival time
timeFrame: 6-month
measure: Survival Time
timeFrame: 6-month
measure: Uptake of CRAG screening and preemptive treatment
timeFrame: baseline
measure: Time from CRAG+ test to receipt of fluconazole therapy
timeFrame: Days from CD4 testing
measure: All-cause discontinuation of fluconazole
timeFrame: 6-month
measure: Percentage of participants with symptomatic cryptococcal meningitis
timeFrame: baseline
measure: Risk factors for symptomatic cryptococcal meningitis
timeFrame: baseline
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Infectious Disease Institute, Makerere University
city: Kampala
country: Uganda
facility: Kampala Capital Council Authority Clinics
Study officials:
affiliation: Makerere University
name: David B Meya, MMed
role: PRINCIPAL_INVESTIGATOR
affiliation: Infectious Disease Institute
name: Radha Rajasingham, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.