Cryptococcal MeningitisNCT02098525
Clinical Outcomes of Cryptococcal Meningitis Among HIV-infected Patients in the Era of Antiretroviral Therapy
An observational study of Cryptococcal Meningitis and HIV/AIDS, run by Mahidol University at 1 site in Thailand.
Trial summary
Cryptococcal meningitis is one of the most common central nervous system infections among HIV-infected patients. The outcome is generally severe. This study aims to determine long-term survival rate among HIV-infected CM patients in the era of antiretroviral therapy (ART). Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Cryptococcal Meningitis, HIV/AIDS
- How many people
- 195 participants
- Where
- 1 siteThailand
- Study dates
- Nov 2013to Dec 2013
- 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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population is all adult HIV positive patients with CM at Ramathibodi Hospital, Mahidol University.
Who may be able to join
- HIV-infected patients diagnosed by positive results of 2 different ELISA tests, 1 ELISA test accompanied with 1 HIV-PCR test, or 1 ELISA test accompanied with 1 Western blot test, whose age was more than 15 years old.
- Newly diagnosed CM during the study period defined by positive culture, positive Indian ink or positive latex agglutination test on CSF with typical symptoms at Ramathibodi Hospital.
Who cannot join
- Patients who had other known CNS co-infection or other significant concurrent CNS diseases which might influence on outcome of CM.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Bangkok, Bangkok, 10400
About this study
Cryptococcal meningitis is one of the most common central nervous system infections among HIV-infected patients. The outcome is generally severe. This study aims to determine long-term survival rate among HIV-infected CM patients in the era of antiretroviral therapy (ART). The secondary objectives are to clarify outcomes of CM and determine prognostic factors.
Read the detailed description
Study site:
The study are conducted at the Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Sample size calculation:
The sample size is obtained by using EPI Info program. Anticipated population proportion P which will be the major outcome of CM, the survival rate was 63% in Thailand (Chottanapund S, Singhasivanon P, Kaewkungwal J, Chamroonswasdi K, Manosuthi W. Survival time of HIV-infected patients with cryptococcal meningitis. J Med Assoc Thai. 2007 Oct;90(10):2104-11. PubMed PMID: 18041430). At the effect size of 80%, confidence level at 95% (P = 0.05), deviation error of allowanced of 5% and 210 expects HIV infected patients with CM during study period at Ramathibodi Hospital, the estimated sample size is 132 cases.
Outcome measurement:
Death case: Death case is CM patient who died for any reason during the period of follow-up.
Survival case: Survival case is CM patient who did not die during the period of follow-up.
Relapse case: This refers to a patient who developed a new episode of CM after clinical manifestations had disappeared and CSF culture had become negative, and confirmed by positive CSF culture for Cryptococcus neoformans.
IRIS case: This refers to a patient who developed a new episode of clinical meningitis after clinical manifestations stemming from a previous episode of CM had disappeared and the patient had been started ART, and defined as negative CSF culture for Cryptococcus neoformans. Alternative etiology which presents symptoms similar to CM must be ruled out.
Clinical outcome parameters:
Short-term outcome: Short-term outcome is defined as the outcome that happened within 1 year of follow up period.
Long-term outcome: Long-term outcome is defined as all outcomes that happened after 1 year of follow up period.
Margin period to evaluate the blood findings at AmB induction therapy initiation is defined as within 3 months from the exact date of AmB induction therapy initiation.
Margin period to evaluate the parameters at AmB induction therapy completion is defined as within 7 days from the exact date of AmB induction therapy completion.
Margin period to evaluate the CSF findings at ART initiation is defined as within 1 month from the exact date of ART initiation.
Margin period to evaluate the blood findings at ART initiation is defined as from 3 months before to 1 month after the exact date of ART initiation.
Margin period to evaluate the parameters at secondary FLCZ prophylaxis completion is defined as within 3 months from the exact date of secondary FLCZ prophylaxis completion.
Research methodology:
The medical records of those diagnosed with HIV associated CM is retrieved from the medical record department in Ramathibodi Hospital. Then the inclusion and exclusion criteria are checked. We review at least 132 cases. The information from the medical records which pass the criteria is extracted and transferred to the case report form. Then data entry is carried out with coding and verified.
Statistical analysis:
The data will be computed by means of the descriptive statistical methods as the following values: frequency distribution, proportion, rate, median and range. To compare demographic and clinical characteristics, we will use chi-square tests or Fisher's exact tests for categorical variables and student's t tests or Mann-Whitney U tests for continuous variables. Cox's proportional hazards model and Kaplan-Meier survival analysis will be used to evaluate factors associated with outcomes. Hazard ratio, odds ratio and 95% CI will be calculated and used as a measure of the strength of the association between the outcome variables and their predictors. A two-tailed alpha level of 0.05 will be used to determine statistical significance. Statistical analyses will be performed with the statistical program, SPSS.
Ethical committee approval:
As a retrospective study, we review patients' medical records only. No patient are directly involved in this study and therefore no informed consent is obtained. The proposal is reviewed by the Ethical Committee of the Faculty of Tropical Medicine, Mahidol University, for clearance. Data collection was started after the protocol is ethically approved.
Confidentiality:
The names or any clues leading to the identification of the patients are not be recorded in CRF (case record form). Only code numbers are recorded in CRF. The information of patient's identification and code number are kept separately. The results are presented as medical data with no personal identifying information. Authorized person helps to collect data.
Research funds:
Funding for the study is provided by the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
- Conditions
- Cryptococcal Meningitis, HIV/AIDS
- Keywords
- Cryptococcal meningitis, HIV/AIDS, Antiretroviral therapy, Prognosis, Thailand
- Medical subject headings
- Meningitis, Cryptococcal, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HIV associated CM patients | The study population is all adult HIV positive patients with CM at Ramathibodi Hospital. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long-term survival rate of CM
To describe long-term survival rate of CM among adult HIV-infected patients in the era of ART.
Measured: Up to 12 years. Cases will be censored at the date of last visit if they are lost to follow up or referred to another hospital, and will be censored at the date of death.
Secondary outcomes (1)
Risk factors of short-term and long-term mortality of CM
To identify risk factors of short-term and long-term mortality of CM.
Measured: Up to 12 years. Cases will be censored at the date of last visit if they are lost to follow up or referred to another hospital, and will be censored at the date of death.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2014 (estimated)
- Study startNov 2013
- Primary completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cryptococcal MeningitisStudies of the same condition, open and under way.
- More trials run by Mahidol UniversityThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 195 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Punnee Pitisuttithum, Mahidol University
- Investigators
- Taiichiro Kobayashi, Dr, Principal investigator, Mahidol UniversityPunnee Pitisuttithum, Prof., Study director, Mahidol UniversityWeerawat Manosuthi, Dr., Study chair, Bamrasnaradura infectious disease hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02098525
- Sponsor's protocol ID
- HIVCM-01
- Status last verified
- Mar 2014
- First submitted
- 18 Mar 2014
- Last updated
- 28 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Outcomes of Cryptococcal Meningitis Among HIV-infected Patients in the Era of Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT02098525
- Acronym / sponsor ID
- HIVCM-01
- Conditions
- Cryptococcal Meningitis, HIV/AIDS
- Keywords
- Cryptococcal meningitis, HIV/AIDS, Antiretroviral therapy, Prognosis, Thailand
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 195 participants (actual)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- Dec 2013 (actual)
- First posted
- 28 Mar 2014 (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.
Cryptococcal meningitis is one of the most common central nervous system infections among HIV-infected patients. The outcome is generally severe. This study aims to determine long-term survival rate among HIV-infected CM patients in the era of antiretroviral therapy (ART). The secondary objectives are to clarify outcomes of CM and determine prognostic factors.
Detailed description
Study site:
The study are conducted at the Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Sample size calculation:
The sample size is obtained by using EPI Info program. Anticipated population proportion P which will be the major outcome of CM, the survival rate was 63% in Thailand (Chottanapund S, Singhasivanon P, Kaewkungwal J, Chamroonswasdi K, Manosuthi W. Survival time of HIV-infected patients with cryptococcal meningitis. J Med Assoc Thai. 2007 Oct;90(10):2104-11. PubMed PMID: 18041430). At the effect size of 80%, confidence level at 95% (P = 0.05), deviation error of allowanced of 5% and 210 expects HIV infected patients with CM during study period at Ramathibodi Hospital, the estimated sample size is 132 cases.
Outcome measurement:
Death case: Death case is CM patient who died for any reason during the period of follow-up.
Survival case: Survival case is CM patient who did not die during the period of follow-up.
Relapse case: This refers to a patient who developed a new episode of CM after clinical manifestations had disappeared and CSF culture had become negative, and confirmed by positive CSF culture for Cryptococcus neoformans.
IRIS case: This refers to a patient who developed a new episode of clinical meningitis after clinical manifestations stemming from a previous episode of CM had disappeared and the patient had been started ART, and defined as negative CSF culture for Cryptococcus neoformans. Alternative etiology which presents symptoms similar to CM must be ruled out.
Clinical outcome parameters:
Short-term outcome: Short-term outcome is defined as the outcome that happened within 1 year of follow up period.
Long-term outcome: Long-term outcome is defined as all outcomes that happened after 1 year of follow up period.
Margin period to evaluate the blood findings at AmB induction therapy initiation is defined as within 3 months from the exact date of AmB induction therapy initiation.
Margin period to evaluate the parameters at AmB induction therapy completion is defined as within 7 days from the exact date of AmB induction therapy completion.
Margin period to evaluate the CSF findings at ART initiation is defined as within 1 month from the exact date of ART initiation.
Margin period to evaluate the blood findings at ART initiation is defined as from 3 months before to 1 month after the exact date of ART initiation.
Margin period to evaluate the parameters at secondary FLCZ prophylaxis completion is defined as within 3 months from the exact date of secondary FLCZ prophylaxis completion.
Research methodology:
The medical records of those diagnosed with HIV associated CM is retrieved from the medical record department in Ramathibodi Hospital. Then the inclusion and exclusion criteria are checked. We review at least 132 cases. The information from the medical records which pass the criteria is extracted and transferred to the case report form. Then data entry is carried out with coding and verified.
Statistical analysis:
The data will be computed by means of the descriptive statistical methods as the following values: frequency distribution, proportion, rate, median and range. To compare demographic and clinical characteristics, we will use chi-square tests or Fisher's exact tests for categorical variables and student's t tests or Mann-Whitney U tests for continuous variables. Cox's proportional hazards model and Kaplan-Meier survival analysis will be used to evaluate factors associated with outcomes. Hazard ratio, odds ratio and 95% CI will be calculated and used as a measure of the strength of the association between the outcome variables and their predictors. A two-tailed alpha level of 0.05 will be used to determine statistical significance. Statistical analyses will be performed with the statistical program, SPSS.
Ethical committee approval:
As a retrospective study, we review patients' medical records only. No patient are directly involved in this study and therefore no informed consent is obtained. The proposal is reviewed by the Ethical Committee of the Faculty of Tropical Medicine, Mahidol University, for clearance. Data collection was started after the protocol is ethically approved.
Confidentiality:
The names or any clues leading to the identification of the patients are not be recorded in CRF (case record form). Only code numbers are recorded in CRF. The information of patient's identification and code number are kept separately. The results are presented as medical data with no personal identifying information. Authorized person helps to collect data.
Research funds:
Funding for the study is provided by the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HIV associated CM patients | – | –The study population is all adult HIV positive patients with CM at Ramathibodi Hospital. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population is all adult HIV positive patients with CM at Ramathibodi Hospital, Mahidol University.
Key inclusion criteria (2 listed)
- HIV-infected patients diagnosed by positive results of 2 different ELISA tests, 1 ELISA test accompanied with 1 HIV-PCR test, or 1 ELISA test accompanied with 1 Western blot test, whose age was more than 15 years old.
- Newly diagnosed CM during the study period defined by positive culture, positive Indian ink or positive latex agglutination test on CSF with typical symptoms at Ramathibodi Hospital.
Key exclusion criteria (1 listed)
- Patients who had other known CNS co-infection or other significant concurrent CNS diseases which might influence on outcome of CM.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Long-term survival rate of CM
Time frame: Up to 12 years. Cases will be censored at the date of last visit if they are lost to follow up or referred to another hospital, and will be censored at the date of death.
To describe long-term survival rate of CM among adult HIV-infected patients in the era of ART.
1 secondary outcome
Risk factors of short-term and long-term mortality of CM
Time frame: Up to 12 years. Cases will be censored at the date of last visit if they are lost to follow up or referred to another hospital, and will be censored at the date of death.
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 28 Mar 2014.
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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.
Taiichiro Kobayashi, Dr principal investigator
Mahidol University
Punnee Pitisuttithum, Prof. study director
Mahidol University
Weerawat Manosuthi, Dr. study chair
Bamrasnaradura infectious disease 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 and HIV/AIDS, run by Mahidol University at 1 site in Thailand.
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 2 inclusion and 1 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 28 Mar 2014. 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 Thailand. 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?
Long-term survival rate of CM (time frame: Up to 12 years. Cases will be censored at the date of last visit if they are lost to follow up or referred to another hospital, and will be censored at the date of death.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Mar 2014.