Histoplasmosis Induction and Consolidation Therapy Factorial Randomized Clinical Trial (Histo-FACT)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 664
- 试验地点
- 4
- 主要终点
- Mortality at 2 weeks
研究概览
简要总结
The purpose of the study is threefold:
- 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.
- 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
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Total Consolidation - Standard of Care
12 months total (e.g., 6 additional months) of itraconazole or posaconazole based on assignment from Aim 2
干预措施: WHO-recommended SOC Itraconazole (Drug)
Consolidation Therapy - Experimental
posaconazole
干预措施: Posaconazole (Drug)
Total Consolidation - Experimental
6 months total (e.g., 0 additional months) of itraconazole or posaconazole based on assignment from Aim 2.
干预措施: WHO-recommended SOC Itraconazole (Drug)
Total Consolidation - Experimental
6 months total (e.g., 0 additional months) of itraconazole or posaconazole based on assignment from Aim 2.
干预措施: Posaconazole (Drug)
Induction Therapy - Experimental
Single high-dose (10mgkg) of LAmB B
干预措施: LAmB B (Drug)
Consolidation Therapy - Standard of Care
SOC itraconazole
干预措施: WHO-recommended SOC Itraconazole (Drug)
Total Consolidation - Standard of Care
12 months total (e.g., 6 additional months) of itraconazole or posaconazole based on assignment from Aim 2
干预措施: Posaconazole (Drug)
Induction Therapy - Standard of Care
SOC daily standard dose (3mg/kg) LAmB
干预措施: World Health Organization (WHO)-recommended SOC (Drug)
结局指标
主要结局
Mortality at 2 weeks
时间窗: Week 2
Mortality at 26 weeks
时间窗: Week 26
SAE-free survival between 26 and 52 weeks from induction therapy among those who survived 26 weeks
时间窗: Week 52
次要结局
- Aim 1: Hierarchical composite end point(Week 56)
- Aim 2: Hierarchical composite end point(Week 56)