Ignite Creation Date:
2024-05-19 @ 5:35 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06414512
Status:
COMPLETED
Last Update Posted:
2024-05-16
First Post:
2024-05-07
Brief Title:
Optimizing the Dose of Flucytosine for the Treatment of Cryptococcal Meningitis
Sponsor:
University of Minnesota
Organization:
University of Minnesota
Study Overview
Official Title:
Optimizing the Dose of Flucytosine for the Treatment of Cryptococcal Meningitis
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cryptococcal meningitis CM is a fungal infection that causes a severe syndrome of meningitis that is 100 fatal without antifungal therapy Even with antifungal therapy mortality rates remain high especially in Africa where the ongoing HIVAIDS pandemic leads to higher prevalence of cryptococcosis Combination of amphotericin and flucytosine 5-FC is the mainstay of therapy for the initial management of CM Indeed it has even been shown that effective delivery of these therapies in Africa can lower mortality rates by 90
This is a prospective open-label trial to compare the efficacy and safety of lower doses of 5FC during induction therapy to historical controls with standard 5FC dosing Participants in the trial will receive 60mgkgday of 5-FC in 3 divided doses for 10 days Single-dose liposomal amphotericin 10mgkg is preferred if available Amphotericin B 07-10 mgkgday may be used if needed Historical controls drawn from the AMBITION trial will be used as a comparison group selected weighted by inclusionexclusion criteria baseline characteristics and therapies received Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mgkgday and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazoleday for 7 days The intervention group received single- dose liposomal amphotericin plus 5-FC and fluconazole 1200 mgday
All participants will receive fluconazole 1200mgday during consolidation therapy from day 1 to 14 then 800mgday from day 15 to 10 weeks and 200mgday after 10 weeks All participants will receive lumbar punctures at diagnosis day 3 day 5-7 day 10-14 and additionally as required for control of intracranial pressure and documentation of CSF sterilization Controls from Ambition will be matched for the same LP windows Therapeutic LPs conducted during the first week have a 70 relative survival benefit
This is a prospective open-label trial to compare the efficacy and safety of lower doses of 5FC during induction therapy to historical controls with standard 5FC dosing Participants in the trial will receive 60mgkgday of 5-FC in 3 divided doses for 10 days Single-dose liposomal amphotericin 10mgkg is preferred if available Amphotericin B 07-10 mgkgday may be used if needed Historical controls drawn from the AMBITION trial will be used as a comparison group selected weighted by inclusionexclusion criteria baseline characteristics and therapies received Induction therapy for control group participants followed the 2018 WHO cryptococcal guidelines with 7 days of 5-FC 100mgkgday and 7 days of IV Amphotericin deoxycholate followed by 1200mg fluconazoleday for 7 days The intervention group received single- dose liposomal amphotericin plus 5-FC and fluconazole 1200 mgday
All participants will receive fluconazole 1200mgday during consolidation therapy from day 1 to 14 then 800mgday from day 15 to 10 weeks and 200mgday after 10 weeks All participants will receive lumbar punctures at diagnosis day 3 day 5-7 day 10-14 and additionally as required for control of intracranial pressure and documentation of CSF sterilization Controls from Ambition will be matched for the same LP windows Therapeutic LPs conducted during the first week have a 70 relative survival benefit
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None