The purpose of the study is threefold:
1. Assess the safety and efficacy of a single high-dose intravenous (LAmB 10mg/kg) compared to the SOC daily dosing (3mg/kg) of the same medication for induction therapy in moderate to severe histoplasmosis. 2. Assess the safety and efficacy of oral posaconazole 300mg delayed-release tablets three times daily for two days then once daily for consolidation therapy compared to SOC oral itraconazole 200 mg capsules three times daily for three days then twice daily in moderate to severe histoplasmosis 3. Assess the safety and efficacy of 6 months of consolidation therapy compared to the SOC 12 months of consolidation therapy in persons with HIV on appropriate antiretroviral therapy.
Age ≥18 years
Hospitalized with suspected histoplasmosis b
Diagnosis of confirmed or probable histoplasmosis (via positive Histoplasma antigen test, culture, histopathology or microscopy)
Provision of Informed Consent by participant or surrogate c
Previous diagnosis of histoplasmosis
Pregnant persons (all persons who could potentially be pregnant will have a pregnancy test prior to enrollment, and if negative, must agree to contraception for the duration of the study)
Breastfeeding and unable to stop for the duration of the study
Renal impairment (serum creatinine or blood urea nitrogen (BUN) >2.0x upper limit of normal)
Sequential
LAmB B
Drugintravenous liposomal amphotericin B (10mg/kg)
Posaconazole
DrugPosaconazole delayed-release tabs, 300mg twice daily on day 1 then once daily
World Health Organization (WHO)-recommended SOC
Drugdaily intravenous liposomal amphotericin B 3mg/kg, for 2 weeks or at least 7 days if felt stable for discharge per the clinician
WHO-recommended SOC Itraconazole
Drug200mg capsules three times daily x 3 days then twice daily
6
Treatment groupsSee each treatment group below.
Mortality at 2 weeks
Mortality at 26 weeks
SAE-free survival between 26 and 52 weeks from induction therapy among those who survived 26 weeks
Aim 1: Hierarchical composite end point
Consisting of the following in a hierarchical order: 5: Death within 10 weeks or lost to follow up in the first 1 week 4: Serious Adverse event within 10 weeks 3: Grade 4 laboratory abnormality at week two visit or discontinuation of medication due to intolerance during the first 10 weeks 2: Grade 3 laboratory abnormality at week two visit 1: Alive at the end of the study period without one of the above events
Aim 2: Hierarchical composite end point
Consisting of the following in a hierarchical order: 5: Death within the study period 4: Serious Adverse event within 26 weeks 3: Grade 4 laboratory abnormality through week 26 or discontinuation of medication due to intolerance during the first 26 weeks 2: Grade 3 laboratory abnormality through week 26 or or lost to follow up after the first week 1: Alive at the end of the study period without one of the above events
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University of Minnesota
Lead sponsor
Federal University of Health Science of Porto Alegre
Collaborator
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