Cryptococcal MeningitisCryptoARTNCT02434172
CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa
An observational study of Cryptococcal Meningitis, run by University of Zimbabwe at 1 site in Zimbabwe.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cryptococcal Meningitis
- What is being tested?
- Pre-emptive screening and treatment for cryptococcal disease
- How many people
- 1,333 participants
- Where
- 1 siteZimbabwe
- Study dates
- Apr 2015to Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Cryptococcal Meningitis
- Being tested
- Pre-emptive screening and treatment for cryptococcal disease
- Keywords
- HIV, Cryptococcus, Lateral Flow Assay, sub-Saharan Africa, Screening, treatment, cryptococcal meningitis
- Medical subject headings
- Meningitis, Cryptococcal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-emptive screening and treatment for cryptococcal diseaseOther
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Pre-emptive screening and treatment for cryptococcal disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
12- month survival in CrAg-positive persons vs. CrAg-negative persons screened
Measured: 12 months
Secondary outcomes (11)
Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4≤100 cells/mm3 in an urban population in Zimbabwe
Measured: 24 months
Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs
Measured: 24 months
Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs
Measured: 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
Measured: 24 months
12-month survival among individuals with CD4≤100 cells/mm3 prior to implementation of CrAg screening program using historical controls
Retrospective analysis
Measured: 24 months
Cost of implementation of CrAg screening among individuals with CD4≤100 cells/mm3
Measured: 24 months
Cryptococcus-associated mortality among individuals with CD4≤100 cells/mm3,
Measured: 24 months
Incidence of cryptococcal and non-cryptococcal IRIS
Measured: 24 months
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.
Measured: 24 months
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.
Measured: 24 months
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2015 (estimated)
- Study startApr 2015
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cryptococcal MeningitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,333 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zimbabwe
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Chiratidzo Ndhlovu, University of Zimbabwe
- Investigators
- Chiratidzo E Ndhlovu, MBBS, MSc, Principal investigator, University of Zimbabwe College of Health SciencesAzure T Makadzange, MD DPhil, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02434172
- Sponsor's protocol ID
- 1U01GH000737-01
- Acronym
- CryptoART
- Status last verified
- Oct 2018
- First submitted
- 24 Apr 2015
- Last updated
- 12 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kouamou V, Gundidza P, Ndhlovu CE, Makadzange AT; CryptoART Study Team. Effects of Gender and Baseline CD4 Count on Post-Treatment CD4 Count Recovery and Outcomes in Patients with Advanced HIV Disease: A Retrospective Cohort Study. AIDS Res Hum Retroviruses. 2023 Jul;39(7):340-349. doi: 10.1089/AID.2022.0117. Epub 2023 Apr 26.
PubMed 36924288Boyd K, Kouamou V, Hlupeni A, Tangwena Z, Ndhlovu CE, Makadzange AT; CryptoART Study Team. Diagnostic Accuracy of Point of Care Cryptococcal Antigen Lateral Flow Assay in Fingerprick Whole Blood and Urine Samples for the Detection of Asymptomatic Cryptococcal Disease in Patients with Advanced HIV Disease. Microbiol Spectr. 2022 Aug 31;10(4):e0107522. doi: 10.1128/spectrum.01075-22. Epub 2022 Aug 4.
PubMed 35924841
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02434172
- Acronym / sponsor ID
- CryptoART / 1U01GH000737-01
- Conditions
- Cryptococcal Meningitis
- Keywords
- HIV, Cryptococcus, Lateral Flow Assay, sub-Saharan Africa, Screening, treatment, cryptococcal meningitis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,333 participants (actual)
- Lead sponsor
- University of ZimbabweUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- Apr 2015
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 5 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Screening | – | Other: Pre-emptive screening and treatment for cryptococcal diseaseThere are no arms to the study. All participants will undergo screening. Preemptive treatment will only be provided to those who are CrAg positive. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pre-emptive screening and treatment for cryptococcal diseasePreemptive 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. | Other | Screening |
Primary outcome
12- month survival in CrAg-positive persons vs. CrAg-negative persons screened
Time frame: 12 months
11 secondary outcomes
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
- Derived from this study: PubMed 36924288Kouamou V, Gundidza P, Ndhlovu CE, Makadzange AT; CryptoART Study Team. Effects of Gender and Baseline CD4 Count on Post-Treatment CD4 Count Recovery and Outcomes in Patients with Advanced HIV Disease: A Retrospective Cohort Study. AIDS Res Hum Retroviruses. 2023 Jul;39(7):340-349. doi: 10.1089/AID.2022.0117. Epub 2023 Apr 26.
- Derived from this study: PubMed 35924841Boyd K, Kouamou V, Hlupeni A, Tangwena Z, Ndhlovu CE, Makadzange AT; CryptoART Study Team. Diagnostic Accuracy of Point of Care Cryptococcal Antigen Lateral Flow Assay in Fingerprick Whole Blood and Urine Samples for the Detection of Asymptomatic Cryptococcal Disease in Patients with Advanced HIV Disease. Microbiol Spectr. 2022 Aug 31;10(4):e0107522. doi: 10.1128/spectrum.01075-22. Epub 2022 Aug 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chiratidzo E Ndhlovu, MBBS, MSc principal investigator
University of Zimbabwe College of Health Sciences
Azure T Makadzange, MD DPhil principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cryptococcal Meningitis, run by University of Zimbabwe at 1 site in Zimbabwe.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12- month survival in CrAg-positive persons vs. CrAg-negative persons screened (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02434172, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2018.