Histoplasmosis Induction and Consolidation Therapy Factorial Randomized Clinical Trial (Histo-FACT)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Histoplasmosis
• Intervention / Treatment: Drug: LAmB B; Drug: World Health Organization (WHO)-recommended SOC; Drug: Posaconazole; Drug: WHO-recommended SOC Itraconazole

• Study Type: Interventional
• Enrollment (Estimated): 664
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Nathan Bahr, MD; Phone Number: 612-624-9996; Email: bahrx026@umn.edu

Study Locations

• Brazil
  • Porto Alegre, Brazil
    • Universidade Federal de Ciências da Saúde de Porto Alegre
    • Contact: Alessandro Pasqualotto; Email: pasqualotto@santacasa.org.br
• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
      • Contact: Nathan Bahr; Email: bahrx026@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)
• Allergy or contraindication to a study medicine
• More than one dose of an amphotericin product in the prior 7 days
• Suspected central nervous system involvement of histoplasmosis
• Likely to die in the next 48 hours in the judgment of the investigator
• Unlikely to follow up for the duration of the study in the judgement of the investigator
• Significant drug-drug interaction with itraconazole or posaconazole (such as rifampin in persons with TB)
• Current diagnosis of cryptococcosis or leishmaniasis
• QTc interval consistently >450 milliseconds
• Prisoners
• Unable to take oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Induction Therapy - Experimental; Single high-dose (10mgkg) of LAmB B	Drug: LAmB B; intravenous liposomal amphotericin B (10mg/kg)
Active Comparator: Induction Therapy - Standard of Care; SOC daily standard dose (3mg/kg) LAmB	Drug: World Health Organization (WHO)-recommended SOC; daily intravenous liposomal amphotericin B 3mg/kg, for 2 weeks or at least 7 days if felt stable for discharge per the clinician
Experimental: Consolidation Therapy - Experimental; posaconazole	Drug: Posaconazole; Posaconazole delayed-release tabs, 300mg twice daily on day 1 then once daily
Active Comparator: Consolidation Therapy - Standard of Care; SOC itraconazole	Drug: WHO-recommended SOC Itraconazole; 200mg capsules three times daily x 3 days then twice daily
Experimental: Total Consolidation - Experimental; 6 months total (e.g., 0 additional months) of itraconazole or posaconazole based on assignment from Aim 2.	Drug: Posaconazole; Posaconazole delayed-release tabs, 300mg twice daily on day 1 then once daily; Drug: WHO-recommended SOC Itraconazole; 200mg capsules three times daily x 3 days then twice daily
Active Comparator: Total Consolidation - Standard of Care; 12 months total (e.g., 6 additional months) of itraconazole or posaconazole based on assignment from Aim 2	Drug: Posaconazole; Posaconazole delayed-release tabs, 300mg twice daily on day 1 then once daily; Drug: WHO-recommended SOC Itraconazole; 200mg capsules three times daily x 3 days then twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality at 2 weeks	Week 2
Mortality at 26 weeks	Week 26
SAE-free survival between 26 and 52 weeks from induction therapy among those who survived 26 weeks	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 56
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	Week 56

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Federal University of Health Science of Porto Alegre
• Investigators: Principal Investigator: Nathan Bahr, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Actual): December 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Histoplasmosis; Organizations; Health Care Economics and Organizations; United Nations; International Agencies; posaconazole; World Health Organization
• Other Study ID Numbers: IDIM-2025-33491

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No