Clinical trial NCT03267407: Vietnam Cryptococcal Retention in Care Study - Version 2.1
Official title: Vietnam Cryptococcal Retention in Care Study (CRICS) - Version 2.1
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: HIV/AIDS
Cryptococcal Meningitis
Opportunistic Infections, HIV Related
Cryptococcosis
Mycosis; Opportunistic
Mycosis Fungoides
Lead sponsor: National Hospital for Tropical Diseases, Hanoi, Vietnam
Sponsor class: OTHER_GOV
Collaborators: name: Centers for Disease Control and Prevention
name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
First posted: 2017-08-30
Enrollment: 1184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced HIV infection (CD4\<100 cells/microliters) who are eligible to inclusion and exclusion criteria are recruited and followed up into the study.

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.

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

Eligibility 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

Primary outcomes:
measure: Proportion of HIV-infected adults who have CD4 count ≤ 100 cells/μL
timeFrame: August 2015 to March 2017
measure: Prevalence of CrAg-positivity among HIV-infected patients with CD4 ≤100 cells/μL
timeFrame: August 2015 to March 2017
measure: 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
timeFrame: August 2015 to March 2017
measure: Twelve (12) month all-causes and cryptococcal meningitis (CM)-related mortality among patients who screen CrAg-positive and CrAg-negative
timeFrame: August 2015 to March 2017
Secondary outcomes:
measure: Twelve (12) month retention among patients who screen CrAg-positive and CrAg-negative
timeFrame: August 2015 to March 2017
measure: Challenges associated with implementation of routine plasma CrAg screening in clinics providing HIV care
timeFrame: August 2015 to March 2018
measure: Lessons learned with participating sites
timeFrame: August 2015 to March 2018
measure: Total costs and unit cost per person screened, per CrAg+ treated by site, lab facility type, and cost component.
timeFrame: August 2015 to March 2017
measure: Incremental cost-effectiveness ratio (cost per CM death averted and cost per quality adjusted life year (QALY))
timeFrame: August 2015 to March 2017
measure: Total cost savings and amount of financial resources required to implement CrAg screening
timeFrame: August 2015 to March 2017
measure: Proportion of stored samples that test positive for TmAg
timeFrame: August 2015 to March 2017
measure: Six (6) and twelve (12) month all-causes and Talaromyces marneffei-related mortality among patients who screen TmAg-positive and TmAg-negative
timeFrame: August 2015 to March 2017
Other outcomes:
Locations:
city: Hanoi
country: Vietnam
facility: National Hospital for Tropical Diseases
Study officials:
affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam
name: Kinh V Nguyen, MD
role: PRINCIPAL_INVESTIGATOR
References: