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

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ClinicalTrials.gov Identifier: NCT02434172
Recruitment Status : Completed
First Posted : May 5, 2015
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
Chiratidzo Ndhlovu, University of Zimbabwe

Tracking Information
First Submitted Date April 24, 2015
First Posted Date May 5, 2015
Last Update Posted Date October 12, 2018
Study Start Date April 2015
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 29, 2015)
12- month survival in CrAg-positive persons vs. CrAg-negative persons screened [ Time Frame: 12 months ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 29, 2015)
  • Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4≤100 cells/mm3 in an urban population in Zimbabwe [ Time Frame: 24 months ]
  • Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs [ Time Frame: 24 months ]
  • Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs [ Time Frame: 24 months ]
  • 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 [ Time Frame: 24 months ]
  • 12-month survival among individuals with CD4≤100 cells/mm3 prior to implementation of CrAg screening program using historical controls [ Time Frame: 24 months ]
    Retrospective analysis
  • Cost of implementation of CrAg screening among individuals with CD4≤100 cells/mm3 [ Time Frame: 24 months ]
  • Cryptococcus-associated mortality among individuals with CD4≤100 cells/mm3, [ Time Frame: 24 months ]
  • Incidence of cryptococcal and non-cryptococcal IRIS [ Time Frame: 24 months ]
  • Barriers to uptake of diagnostic LP by individuals with asymptomatic cryptococcal antigenemia. [ Time Frame: 24 months ]
    Questionnaire will be administered to participants who are serum cryptococcal antigen positive who decline to undergo LP.
  • Inflammatory cytokines and functional impairments in antigen specific T cells that are associated with the development of cryptococcal antigenemia and meningitis. [ Time Frame: 24 months ]
    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.
  • 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. [ Time Frame: 24 months ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa
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
Brief 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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Plasma, and peripheral blood mononuclear cells
Sampling Method Non-Probability Sample
Study Population

The study will recruit Asymptomatic participants with severe immunosuppression at risk of cryptococcal disease. The individuals will have a CD4 count <100cells/mm3 and can be ART naive or ART experienced with no symptoms of active Cryptococcal disease.

They will be recruited from outpatient HIV/ART clinics.

Condition Cryptococcal Meningitis
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.
Study Groups/Cohorts Screening
There are no arms to the study. All participants will undergo screening. Preemptive treatment will only be provided to those who are CrAg positive.
Intervention: Other: Pre-emptive screening and treatment for cryptococcal disease
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: October 11, 2018)
1333
Original Estimated Enrollment
 (submitted: April 29, 2015)
1600
Actual Study Completion Date June 2017
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Zimbabwe
Removed Location Countries  
 
Administrative Information
NCT Number NCT02434172
Other Study ID Numbers 1U01GH000737-01( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Chiratidzo Ndhlovu, University of Zimbabwe
Study Sponsor University of Zimbabwe
Collaborators Centers for Disease Control and Prevention
Investigators
Principal Investigator: Chiratidzo E Ndhlovu, MBBS, MSc University of Zimbabwe College of Health Sciences
Principal Investigator: Azure T Makadzange, MD DPhil Massachusetts General Hospital
PRS Account University of Zimbabwe
Verification Date October 2018