Operational Research for Cryptococcal Antigen Screening

NCT01535469 | Completed Phase 4 DMC

• 2 other identifiers: HS1254U01GH000517
• Study Type: interventional
• Target: 3,049
• Locations: 1 country
• Sites: 2

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

Conditions

Cryptococcal Meningitis; Cryptococcus Neoformans; Cryptococcosis

Keywords

cryptococcal meningitis; hiv; aids; implementation science; stepped wedge design; retention-in-care

Outcome Measures

Primary Outcomes (1)

• Retention in care

  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.

  6-month

Secondary Outcomes (7)

• Cryptococcal meningitis-free survival time

  6-month

• Survival Time

  6-month

• Uptake of CRAG screening and preemptive treatment

  baseline

• Time from CRAG+ test to receipt of fluconazole therapy

  Days from CD4 testing

• All-cause discontinuation of fluconazole

  6-month

Study Arms (1)

CrAg Screening and Fluconazole

EXPERIMENTAL

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

Drug: Fluconazole

Interventions

Fluconazole DRUG

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

Also known as: Diflucan

CrAg Screening and Fluconazole

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• CD4≤100 cells/mcL
• Cryptococcal antigen (CRAG) positive
• age \>14 years

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Infectious Disease Institute, Makerere University

Kampala, Uganda

Location

Kampala Capital Council Authority Clinics

Kampala, Uganda

Location

Related Publications (3)

• 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.

  PMID: 22410867 BACKGROUND

• 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.

  PMID: 20597693 BACKGROUND

• 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.

  PMID: 30399034 RESULT

Related Links

• Infectious Disease Institute

MeSH Terms

Conditions

Meningitis, Cryptococcal; Cryptococcosis; Acquired Immunodeficiency Syndrome

Interventions

Fluconazole

Condition Hierarchy (Ancestors)

Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David B Meya, MMed

  Makerere University

  PRINCIPAL INVESTIGATOR

• Radha Rajasingham, MD

  Infectious Disease Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 17, 2012
• Study Start: July 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Upon request
• Access Criteria: Upon request

Locations

UG (2)