Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06525389
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-24
Brief Title:
Liposomal Amphotericin B and Flucytosine Antifungal Strategy for Talaromycosis LAmB-FAST
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Liposomal Amphotericin B and Flucytosine Antifungal Strategy for Talaromycosis LAmB-FAST
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LAmB-FAST
Brief Summary:
LAmB-FAST is a factorial randomized controlled trial simultaneously testing two interventions in one trial LAmB-FAST seeks to inform treatment guidelines on the induction and maintenance therapy of HIV-associated talaromycosis formerly called penicilliosis and will answer the following three questions
1 Is induction therapy using a single 10 mgkg dose of liposomal amphotericin B LAmB is more effective than 14 days of the conventional deoxycholate amphotericin B DAmB
2 Is adding flucytosine 5FC to amphotericin B more effective than amphotericin B alone
3 Is HIV viral load guided stopping of itraconazole maintenance therapy as effective as the current CD4 guided strategy in the prevention of talaromycosis relapse
1 Is induction therapy using a single 10 mgkg dose of liposomal amphotericin B LAmB is more effective than 14 days of the conventional deoxycholate amphotericin B DAmB
2 Is adding flucytosine 5FC to amphotericin B more effective than amphotericin B alone
3 Is HIV viral load guided stopping of itraconazole maintenance therapy as effective as the current CD4 guided strategy in the prevention of talaromycosis relapse
Detailed Description:
Talaromycosis formerly known as penicilliosis is caused by the dimorphic fungus Talaromyces marneffei Tm endemic in Southeast Asia where it is a leading the cause of death among people with advanced HIV disease AHD CD4 count 200 cellsmm3 andor WHO disease stage III or IV Despite the mortality on treatment as high as 30 current treatment options are limited to just two drugs amphotericin B deoxycholate DAmB - which has substantial toxicity and itraconazole - which has poor bioavailability
As a roadmap to identify safer and more effective antifungal strategies LAmB-FAST applies major advances made in HIV-associated mycoses to accelerate treatment for HIV-associated talaromycosis First clinical trials in cryptococcosis showed that shorter courses 5 to 7 days of DAmB was as effective and less toxic than the standard 14-day course of DAmB The recent AMBITION cryptococcal meningitis showed that a single 10 mgkg dose of liposomal amphotericin B LAmB was as effective as 7 to 14 days of DAmB but had 30 less toxicity leading to rapid endorsement by the WHO as the first-line therapy for cryptococcal meningitis in 2022 A single LAmB induction therapy strategy has also been demonstrated in a phase II HIV-associated histoplasmosis trial which showed that a single 10 mgkg dose of LAmB had similar mortality compared to 2 doses or 14 daily doses of LAmB Second the addition of flucytosine 5FC to DAmB has been shown to improves fungal clearance in the cerebrospinnal fluid and survival of patients with cryptococcal meningitis These advances in other HIV-associated mycoses lead us to hypothesize that 1 a single 10mgkg dose of LAmB will be superior to 14 days of DAmB and 2 the addition of 5FC will be superior to DAmB or LAmB alone in the induction therapy of talaromyosis
LAmB-FAST will test three related but independent specific aims AIM 1 To determine if a single 10mgkg dose of LAmB is superior to 14 days of DAmB in Tm complication-free survival AIM 2
To determine if combination therapy with 5FC is superior to DAmB or LAmB alone in Tm complication-free survival
The primary outcome for both AIM 1 and AIM 2 is hazard of a composite of death Tm complications and adverse events AEs grade 3 or higher
The secondary outcomes include
1 All-cause mortality
2 Fungal clearance rate over first 14 days
3 A novel 4-scale hierarchical outcome of i Mortality ii Tm complications iii AEs grade 3 iv Quality of life scores
4 Rates of Tm DNA and Tm antigen decline over first 12 weeks
AIM 3 will leverage access to a well-characterized and treated talaromycosis cohort in AIM 1 and AIM 2 to conduct a follow-on nested randomized controlled sub-study testing whether a HIV viral load guided strategy of stopping itraconazole chemoprophylaxis STOP SHORT is non-inferior to the current CD4 guided strategy in the prevention of talaromycosis relapse and death
As a roadmap to identify safer and more effective antifungal strategies LAmB-FAST applies major advances made in HIV-associated mycoses to accelerate treatment for HIV-associated talaromycosis First clinical trials in cryptococcosis showed that shorter courses 5 to 7 days of DAmB was as effective and less toxic than the standard 14-day course of DAmB The recent AMBITION cryptococcal meningitis showed that a single 10 mgkg dose of liposomal amphotericin B LAmB was as effective as 7 to 14 days of DAmB but had 30 less toxicity leading to rapid endorsement by the WHO as the first-line therapy for cryptococcal meningitis in 2022 A single LAmB induction therapy strategy has also been demonstrated in a phase II HIV-associated histoplasmosis trial which showed that a single 10 mgkg dose of LAmB had similar mortality compared to 2 doses or 14 daily doses of LAmB Second the addition of flucytosine 5FC to DAmB has been shown to improves fungal clearance in the cerebrospinnal fluid and survival of patients with cryptococcal meningitis These advances in other HIV-associated mycoses lead us to hypothesize that 1 a single 10mgkg dose of LAmB will be superior to 14 days of DAmB and 2 the addition of 5FC will be superior to DAmB or LAmB alone in the induction therapy of talaromyosis
LAmB-FAST will test three related but independent specific aims AIM 1 To determine if a single 10mgkg dose of LAmB is superior to 14 days of DAmB in Tm complication-free survival AIM 2
To determine if combination therapy with 5FC is superior to DAmB or LAmB alone in Tm complication-free survival
The primary outcome for both AIM 1 and AIM 2 is hazard of a composite of death Tm complications and adverse events AEs grade 3 or higher
The secondary outcomes include
1 All-cause mortality
2 Fungal clearance rate over first 14 days
3 A novel 4-scale hierarchical outcome of i Mortality ii Tm complications iii AEs grade 3 iv Quality of life scores
4 Rates of Tm DNA and Tm antigen decline over first 12 weeks
AIM 3 will leverage access to a well-characterized and treated talaromycosis cohort in AIM 1 and AIM 2 to conduct a follow-on nested randomized controlled sub-study testing whether a HIV viral load guided strategy of stopping itraconazole chemoprophylaxis STOP SHORT is non-inferior to the current CD4 guided strategy in the prevention of talaromycosis relapse and death
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None