Vietnam Cryptococcal Retention in Care Study Version 1.0 (CRICS)

Evaluation of a Public Health Strategy to Improve Survival of HIV Infected Patients

It is hypothesized that implementing plasma CrAg screening in clinics providing routine HIV care will enable identification of Vietnamese adult patients with advanced HIV (CD4 ≤100 cells/μL) who have early cryptococcal disease, enable prompt preemptive treatment with high-dose fluconazole, and improve survival.

Study Overview

• Status: Unknown
• Conditions: Central Nervous System Infections; Central Nervous System Fungal Infections; Meningitis, Cryptococcal; Meningitis, Fungal
• Intervention / Treatment: Drug: Fluconazole

Detailed Description

This is multicenter prospective cohort evaluation of the implementation of a cryptococcal antigen (CrAg) screening program in Vietnam. HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA) and followed up for 12 months with clinical assessments and the collection of routine and supplemental survey data. 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.

• Study Type: Observational
• Enrollment (Anticipated): 2612

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam, 00000
    • National Hospital for Tropical Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Newly registering and ART-naive patients with advanced HIV infection

Description

Inclusion Criteria:

• Aged ≥ 18 years
• Confirmed HIV infection using National Testing Algorithm
• CD4 ≤100 cells/μL
• Able to provide written informed consent

Exclusion Criteria:

• History of prior CM
• Receipt of systemic antifungal medication for more than 4 consecutive weeks within the past 6 months
• Currently taking ART or history of ART for more than 4 weeks within the past year
• Known to be currently pregnant or planning to become pregnant during the study period

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CrAg(+) and CM(+); Patients with symptoms of CNS disease will be treated according to Vietnam national guidelines for HIV/AIDS management.	Drug: Fluconazole; HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole.
CrAg(+) and CM(-); Patients with CrAg(+) and without CM symptoms will be treated with high-dose fluconazole. The initial dosage of fluconazole will be 900 mg taken each day for 2 weeks. This will be followed by fluconazole 450 mg orally each day for 8 weeks. Finally, maintenance treatment with fluconazole 200mg orally each (2 tablets of 100 mg procured especially for the study) day will continue until CD4 >200 cells/µL for at least 6 months.	Drug: Fluconazole; HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole.
CrAg negative; Patients with CrAg negative results will be managed as other HIV positive patients according to the national guidelines	Drug: Fluconazole; HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Six (6) and (12) month all-cause and CM-related mortality among patients who screen CrAg-positive and CrAg-negative	Up to 12 months after recruitment
Proportion of all patients tested for plasma CrAg who have positive results	Up to 12 months after recruitment

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent of patients with HIV-related hospitalizations at 6 and 12 months	12 months after recruitment
Percent of patients with new AIDS-defining OIs/conditions at 6 and 12 months	12 months after recruitment
Causes of death	12 months after recruitment
Six (6) and (12) month retention among patients who screen CrAg-positive and CrAg-negative	12 months after recruitment
Percentage of patients with CD4≤ 100 cells/μL who are lost to follow-up or have incomplete documentation	12 months after recruitment
% of patients with no documented clinic visit 30, 60, and 90 days after date of the scheduled clinic appointment	12 months after recruitment

Collaborators and Investigators

• Sponsor: National Hospital for Tropical Diseases, Hanoi, Vietnam
• Collaborators: Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Nguyen Van Kinh, MD, PhD, National Hospital for Tropical Diseases

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2015
• Primary Completion (Anticipated): March 31, 2018
• Study Completion (Anticipated): March 31, 2018

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimate): January 8, 2015

Study Record Updates

• Last Update Posted (Actual): September 13, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: HIV; Fluconazole; AIDS; cryptococcal meningitis
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Bacterial Infections and Mycoses; Cryptococcosis; Infections; Communicable Diseases; Mycoses; Meningitis; Central Nervous System Fungal Infections; Meningitis, Cryptococcal; Central Nervous System Infections; Meningitis, Fungal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: 1U01GH000758 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Please contact PI for any enquiries

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No