CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa

Cryptococcal Meningitis Clinical Trial

— CryptoART  

Official title:

The CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa Through Early Detection and Prevention of Cryptococcal Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02434172
• Other study ID #: 1U01GH000737-01
• Status: Completed
• Start date: April 2015
• Est. completion date: June 2017

Study information

• Verified date: October 2018
• Source: University of Zimbabwe
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study will determine if the initiation of a 'screen and treat' program for cryptococcal disease among HIV positive individuals decreases morbidity and mortality among individuals with CD4 count < 100 cells/mm3. The study will screen individuals who are asymptomatic for CM and are either ART naïve or ART experienced with CD4 count < 100 cells/mm3.

The introduction of an cheap, easy to use point of care diagnostic test the lateral flow assay will facilitate rapid diagnosis of cryptococcal disease in resource limited settings. The investigators will determine the efficacy of the lateral flow assay in identifying latent and asymptomatic cryptococcal disease. The investigators will determine the efficacy of the test in detecting disease in readily available body fluids such as urine and whole blood obtained via finger-stick method. The investigators will also determine the cost effectiveness of a screen and treat approach for cryptococcal disease in Zimbabwe.

The investigators also wish to understand why some individuals with low CD4 counts reactivate cryptococcal disease and screen positive for cryptococcal antigen (CrAg) while others with similar levels of immunocompromised do not.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1333
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented HIV positive test by standard national algorithm

• CD4 count =100 cells/mm3

• Age > 18 years

• Residence within 50 km of Harare

• Able to provide written informed consent

Exclusion Criteria:

• Presence of clinical symptoms suggestive of meningitis.

• Recent history of CM within 2 weeks of enrollment, i.e., participants within the induction phase of therapy.

• Individuals with severe hepatic injury, jaundice, alanine transferase (ALT) >5x upper limit of normal

• Individuals with renal failure, defined by an estimated Glomerular filtration rate (eGFR) =30 mL/min (using MDRD (Modification of Diet in Renal Disease) equation)

• Currently known to be pregnant

• A negative urine pregnancy test is required for study entry for women with childbearing potential.

• The use of contraception will be recommended to women with childbearing potential while on high dose fluconazole therapy. Referral to family planning services will be given as necessary.

• Previous allergy or other reaction to amphotericin B and/or fluconazole

• Currently enrolled in another clinical trial/study

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• Meningitis
• Meningitis, Cryptococcal

Intervention

Other:
• Pre-emptive screening and treatment for cryptococcal disease
Preemptive screening for cryptococcal disease among individuals with CD4 counts below 100 cells/mm3 with anti fungal therapy for those what are Cryptococcus antigen positive. These participants will be followed longitudinally for 12 months to determine clinical outcome, with their outcome compared with similar patients who are cryptococcal antigen negative, who will also be followed longitudinally for 12 months.

Locations

Country	Name	City	State
Zimbabwe	Parirenyatwa Hospital	Harare

Sponsors (2)

Lead Sponsor	Collaborator
University of Zimbabwe	Centers for Disease Control and Prevention

Country where clinical trial is conducted

Zimbabwe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12- month survival in CrAg-positive persons vs. CrAg-negative persons screened		12 months
Secondary	Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4=100 cells/mm3 in an urban population in Zimbabwe		24 months
Secondary	Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs		24 months
Secondary	Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs		24 months
Secondary	Proportion of individuals with CD4=100 cells/mm3 and a positive CrAg assay who have disseminated cryptococcal infection with either blood infection or CSF involvement		24 months
Secondary	12-month survival among individuals with CD4=100 cells/mm3 prior to implementation of CrAg screening program using historical controls	Retrospective analysis	24 months
Secondary	Cost of implementation of CrAg screening among individuals with CD4=100 cells/mm3		24 months
Secondary	Cryptococcus-associated mortality among individuals with CD4=100 cells/mm3,		24 months
Secondary	Incidence of cryptococcal and non-cryptococcal IRIS		24 months
Secondary	Barriers to uptake of diagnostic LP by individuals with asymptomatic cryptococcal antigenemia.	Questionnaire will be administered to participants who are serum cryptococcal antigen positive who decline to undergo LP.	24 months
Secondary	Inflammatory cytokines and functional impairments in antigen specific T cells that are associated with the development of cryptococcal antigenemia and meningitis.	Analysis will be done by ELISA and Luminex assays, cell culture and flow cytometry techniques, data collected will be entered into a database and analyzed by patient characteristics.	24 months
Secondary	Impact of ART mediated immune reconstitution on the inflammatory cytokine profile and the cryptococcal antigen specific CD4+ T cell response in those with serum and CSF cryptococcal antigenemia compared with those without.	Analysis will be done by ELISA and Luminex assays, cell culture and flow cytometry techniques, data collected will be entered into a database and analyzed by patient characteristics. Data will be longitudinal including baseline characteristics and subsequent follow-up data at 6 months and 12 months.	24 months