Cryptococcal MeningitisPhase 4CryptoNCT00976040
Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis
A Phase 4 study testing Early antiretroviral therapy in people with Cryptococcal Meningitis and HIV Infections, run by Botswana-UPenn Partnership at 1 site in Botswana.
Trial summary
The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Cryptococcal Meningitis, HIV Infections
- What is being tested?
- Early antiretroviral therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteBotswana
- Study dates
- Sep 2009to Dec 2011
- Phase
- Phase 4
- 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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load.
- Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen
- ART naive at the time of enrollment
- 21 years old and above
- Ability and willingness to give written informed consent to participate in the study
- Able (as assessed by the patient's medical team)to initiate amphotericin B for cryptococcal meningitis
- Initiated amphotericin B 72 hours or less prior to assessment for enrollment or not on amphotericin B at the time of assessment for enrollment
- Agrees to obtain outpatient care after discharge within 50 kilometers from Princess Marina Hospital,Scottish Livingstone Hospital and Bamalete Lutheran Hospital
Who cannot join
- Recent (within the past 4 weeks) antifungal use
- Pregnant or breastfeeding
- Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment.
- Bacterial meningitis at the time of assessment for enrollment.
- Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators.
- Judged by study coordinator to be likely to initiate chemotherapy or any other immunomodulatory therapy prior to the 4 week LP.
- Imprisoned.
Trial locations and contacts
1 site in 1 country.
Botswana1 site
Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital
Gaborone,Ramotswa,Molepolole
About this study
Official title: A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis
The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis.
The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment.
Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.
- Conditions
- Cryptococcal Meningitis, HIV Infections
- Being tested
- Early antiretroviral therapy
- Keywords
- HIV-1, Africa, Botswana, Highly active antiretroviral therapy, treatment naive
- Medical subject headings
- Meningitis, Cryptococcal, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early antiretroviral therapyOther
The intervention is early initiation of antiretroviral therapy after diagnosis of Cryptococcal meningitis.
In the intervention/experimental arm, triple-drug highly active antiretroviral therapy regimens will be initiated within 7 days of diagnosis of Cryptococcal meningitis.
| Study group | Role | What they receive |
|---|---|---|
| Early antiretroviral therapy | Experimental | Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment. Receives: Other: Early antiretroviral therapy |
| Standard antiretroviral therapy | No intervention | Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the CSF CFUs between the immediate and standard ART initiation groups
Measured: 4 weeks
Secondary outcomes (3)
Grade 3 or 4 adverse events
each participant is followed up for 6 months after the initiation of HAART
Measured: 6 months
Clearance of C. neoformans antigen from CSF and blood.
Measured: 6 months
Change in the number of peripheral blood mononuclear cells responding to C. neoformans
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionNov 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Botswana-UPenn Partnership
- Sponsor type
- University, hospital or other
- Collaborators
- Doris Duke Charitable Foundation, University of Pennsylvania
- Responsible party
- Principal investigator, Gregory Bisson, Botswana-UPenn Partnership
- Investigators
- Gregory P Bisson, MD,MSCE, Principal investigator, Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaPablo Tebas, MD, Principal investigator, Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00976040
- Sponsor's protocol ID
- THE BOTSHELO STUDY
- Acronym
- Crypto
- Status last verified
- Feb 2012
- First submitted
- 11 Sep 2009
- Last updated
- 7 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bisson GP, Molefi M, Bellamy S, Thakur R, Steenhoff A, Tamuhla N, Rantleru T, Tsimako I, Gluckman S, Ravimohan S, Weissman D, Tebas P. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis. 2013 Apr;56(8):1165-73. doi: 10.1093/cid/cit019. Epub 2013 Jan 29.
PubMed 23362285
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis
- ClinicalTrials.gov ID
- NCT00976040
- Acronym / sponsor ID
- Crypto / THE BOTSHELO STUDY
- Conditions
- Cryptococcal Meningitis, HIV Infections
- Keywords
- HIV-1, Africa, Botswana, Highly active antiretroviral therapy, treatment naive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Botswana-UPenn PartnershipUniversity, hospital or other
- Collaborators
- Doris Duke Charitable Foundation, University of Pennsylvania
- Study start
- Sep 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 14 Sep 2009 (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 goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis.
The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment.
Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early antiretroviral therapy | Experimental | Other: Early antiretroviral therapySubjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment. |
| Standard antiretroviral therapy | No intervention | –Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load.
- Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen
- ART naive at the time of enrollment
- 21 years old and above
- Ability and willingness to give written informed consent to participate in the study
Key exclusion criteria (7 listed)
- Recent (within the past 4 weeks) antifungal use
- Pregnant or breastfeeding
- Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment.
- Bacterial meningitis at the time of assessment for enrollment.
- Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators.
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 |
|---|---|---|
| Early antiretroviral therapyThe intervention is early initiation of antiretroviral therapy after diagnosis of Cryptococcal meningitis. In the intervention/experimental arm, triple-drug highly active antiretroviral therapy regimens will be initiated within 7 days of diagnosis of Cryptococcal meningitis. | Other | Early antiretroviral therapy |
Primary outcome
Change in the CSF CFUs between the immediate and standard ART initiation groups
Time frame: 4 weeks
3 secondary outcomes
Grade 3 or 4 adverse events
Time frame: 6 months
Clearance of C. neoformans antigen from CSF and blood.
Time frame: 6 months
Change in the number of peripheral blood mononuclear cells responding to C. neoformans
Time frame: 4 weeks
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 7 Feb 2012.
- Derived from this study: PubMed 23362285Bisson GP, Molefi M, Bellamy S, Thakur R, Steenhoff A, Tamuhla N, Rantleru T, Tsimako I, Gluckman S, Ravimohan S, Weissman D, Tebas P. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis. 2013 Apr;56(8):1165-73. doi: 10.1093/cid/cit019. Epub 2013 Jan 29.
Related trials for Cryptococcal Meningitis
RecruitingObservational study
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Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ Lymphocytopenia, Cryptococcal Meningitis
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Optimizing Care for Cryptococcal Antigenemia: Evaluation of Short Course Fluconazole and ART Timing Among CrAg+ Persons With Low Titers
Cryptococcal Antigenemia, HIV-1-infection
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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.
Gregory P Bisson, MD,MSCE principal investigator
Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Pablo Tebas, MD principal investigator
Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Early antiretroviral therapy in people with Cryptococcal Meningitis and HIV Infections, run by Botswana-UPenn Partnership at 1 site in Botswana.
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 8 inclusion and 7 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 7 Feb 2012. 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 Botswana. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change in the CSF CFUs between the immediate and standard ART initiation groups (time frame: 4 weeks). 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 NCT00976040, which also lists 1 linked publication.
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 7 Feb 2012.