Vietnam Cryptococcal Retention in Care Study - Version 2.1

Vietnam Cryptococcal Retention in Care Study (CRICS) - Version 2.1

Sponsors

Lead Sponsor: National Hospital for Tropical Diseases, Hanoi, Vietnam

Collaborator: Centers for Disease Control and Prevention
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Source National Hospital for Tropical Diseases, Hanoi, Vietnam
Brief Summary

This is a multicenter prospective cohort evaluation of the implementation of a cryptococcal antigen (CrAg) screening program at selected outpatient HIV clinics (OPCs) and network laboratories in Vietnam.

Detailed Description

The project will be implemented in 2 phases; Phase 1: From August 2015 to March 2017 [projected], HIV-infected patients who present for HIV care and undergo CD4 testing will be reviewed to determine the proportion of newly presenting patients with advanced disease (CD4 ≤100 cells/μL). Reflex CrAg screening will be performed using Lateral Flow Assay (LFA) for those with CD4≤100 cells/μL, per Vietnam national guidelines.

Patients with CD4≤100 cells/μL who present for antiretroviral treatment (ART) at a study OPCs—CRICS Sites— will be recruited into the longitudinal study and followed up with assessments and the collection of routine and supplemental data for 12 months or through September 2017 (whichever comes sooner). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole. Those with symptoms of CNS disease will be treated according to national guidelines. Survival, retention in care, and other clinical outcomes will be documented for patients who test CrAg-positive and are treated with fluconazole and those who test CrAg-negative. Data from those tested at participating labs but not eligible for enrollment in the longitudinal study will contribute to the estimation of the prevalence of CrAg.

Phase 2: From April 2017 to September 2017, a cost and cost-effectiveness analysis of CrAg screening will be conducted, a routine screening will be continued at existing sites and expanded to additional sites (preferentially to hospitals affiliated with Phase 1 OPCs and to other OPCs whose CD4 testing is conducted at laboratories already conducting CrAg screening as part of Phase 1). CrAg tests will also be made available to screen all patients with CD4≤100 cells/μL including those who are treatment-experienced. The test will also be made available for use among symptomatic patients for diagnostic purposes, including cerebral spinal fluid (CSF) and blood testing. Investigators will monitor prevalence at each testing site, but screened patients will not be enrolled in longitudinal follow-up. Phase 2 will last for at least 6 months based on the availability of funding and fluconazole for those who screen CrAg positive and the availability/stability of CD4 testing.

[Note that follow up of patients enrolled in Phase 1 will continue during this time period, but is considered to be part of Phase 1 rather than Phase 2. Also, sites included in Phase 2 may change over time as a result of the instability of CD4 testing (e.g., if participating laboratories stop conducting CD4 testing, those sites might no longer be included; if participating laboratories begin CD4 testing for other sites, those sites might be included).]

Overall Status Unknown status
Start Date August 14, 2015
Completion Date March 31, 2018
Primary Completion Date March 31, 2018
Study Type Observational
Primary Outcome
Measure Time Frame
Proportion of HIV-infected adults who have CD4 count ≤ 100 cells/μL August 2015 to March 2017
Prevalence of CrAg-positivity among HIV-infected patients with CD4 ≤100 cells/μL August 2015 to March 2017
Clinical outcomes including common causes of mortality for people living with HIV (PLHIV) with CD4 ≤ 100 cells/μL who are enrolled in a programmatic rollout of screening for CrAg August 2015 to March 2017
Twelve (12) month all-causes and cryptococcal meningitis (CM)-related mortality among patients who screen CrAg-positive and CrAg-negative August 2015 to March 2017
Secondary Outcome
Measure Time Frame
Twelve (12) month retention among patients who screen CrAg-positive and CrAg-negative August 2015 to March 2017
Challenges associated with implementation of routine plasma CrAg screening in clinics providing HIV care August 2015 to March 2018
Lessons learned with participating sites August 2015 to March 2018
Total costs and unit cost per person screened, per CrAg+ treated by site, lab facility type, and cost component. August 2015 to March 2017
Incremental cost-effectiveness ratio (cost per CM death averted and cost per quality adjusted life year (QALY)) August 2015 to March 2017
Total cost savings and amount of financial resources required to implement CrAg screening August 2015 to March 2017
Proportion of stored samples that test positive for TmAg August 2015 to March 2017
Six (6) and twelve (12) month all-causes and Talaromyces marneffei-related mortality among patients who screen TmAg-positive and TmAg-negative August 2015 to March 2017
Enrollment 1184
Condition
Intervention

Intervention Type: Other

Intervention Name: Preemptive high-dose Fluconazole

Description: Patients with advanced HIV diseases are screened for Cryptococcal Antigen using LFA CrAg tests. Then patients with CrAg positivity and without meningitis are given preemptive high-dose fluconazole to prevent the development of cryptococcal meningitis, which is one of the leading cause of death among immunocompromized patients.

Other Name: Preemptive Fluconazole

Eligibility

Sampling Method: Non-Probability Sample

Criteria:

Inclusion Criteria:

- Aged ≥ 18 years (having passed 18th birthday using Western calendar)

- Confirmed HIV infection using National Testing Algorithm

- CD4 ≤100 cells/μL

- Able to provide written informed consent

- Enrolled at and plan to receive ongoing outpatient care at one of the selected study OPCs

Exclusion Criteria:

- History of prior CM

- Receipt of systemic antifungal medication for more than 4 consecutive weeks within the past 6 months

- Receipt of ART for more than 4 consecutive weeks within the past year

- For CrAg-positive patients only: Known to be currently pregnant or planning to become pregnant during the study period

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Kinh V Nguyen, MD Principal Investigator National Hospital for Tropical Diseases, Hanoi, Vietnam
Location
Facility: National Hospital for Tropical Diseases
Location Countries

Vietnam

Verification Date

September 2017

Responsible Party

Type: Principal Investigator

Investigator Affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam

Investigator Full Name: Vu Quoc Dat

Investigator Title: Lead Coordinator

Has Expanded Access No
Condition Browse
Arm Group

Label: CrAg(+) and CM(-)

Description: (1) Patients with CrAg positive without meningitis results will receive preemptive high-dose fluconazole to prevent developing meningitis.

Label: CrAg(+) and CM(+)

Description: (2) Patients with CrAg positive and meningitis results will receive standard treatment for cryptococcal meningitis, following national guidelines.

Label: CrAg(-)

Description: (3) Patients with CrAg negative results will be managed as other HIV infected patients with the standard of care, following national guidelines.

Patient Data Undecided
Study Design Info

Observational Model: Cohort

Time Perspective: Prospective

Source: ClinicalTrials.gov