Efficacy of Combination Baloxovir and Oseltamivir Therapy in Influenza Infected Immunocompromised Hosts
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Changes in viral loads
研究概览
简要总结
This phase II trial studies the effect of baloxavir in combination with oseltamivir in treating severe influenza infection in patients who have previously received a hematopoietic (blood) stem cell transplant or have a hematological malignancy. Baloxavir is an antiviral drug that inhibits the growth of influenza virus, reduces viral load and prevents further influenza infection. Osetamivir is an antiviral drug that blocks enzymes on the surfaces of influenza viruses, interfering with cell release of complete viral particles. Giving baloxavir in combination with oseltamivir may shorten or decrease the intensity of influenza infection compared to oseltamivir alone.
详细描述
PRIMARY OBJECTIVE:
I. To compare the efficacy of baloxavir marboxil (baloxavir) in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 1 from baseline for treatment of severe influenza infections in immunocompromised hosts (such as hematopoietic cell transplant [HCT] recipients and hematological malignancy [HM] patients) and compare the main clinical outcome, complicated hospital stay between the intervention arm and control arm.
SECONDARY OBJECTIVES:
I. To compare the efficacy of baloxavir in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 3, 7, 14 and 30 from baseline.
II. To measure the incidence of baloxavir and oseltamivir resistance, development of lower respiratory tract infections (LRTI), oxygen requirement, respiratory failure, changes in microbiome of the upper airway, length of hospital stay and all-cause mortality at day 30 while on baloxavir and/or oseltamivir in these immunocompromised hosts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hematopoeitic cell transplant recipients OR hematological malignancy patients
- •Diagnosed with influenza ⱡ
- •Evidence of LRTI* or high risk upper respiratory tract infection (URTI)**
- •ⱡ A positive multiplex PCR for influenza is required to confirm a diagnosis of influenza infection.
- •* LRTI will be defined as influenza cases that have evidence of disease below the level of the trachea on either imaging only (possible LRTI), imaging and microbiological evidence of lower airway disease with a bronchoscopy (probable LRTD) or pathological evidence of disease via biopsy (proven LRTI).
- •** High risk URI will be defined as those cases of influenza that do not have microbiological nor radiological evidence of LRTI, yet they have an immunodeficiency scoring index (ISI) of 3 or greater as defined by Shah D et al (19) for HCT recipients or severe neutropenia (ANC ≤500 cells/ml) and/or lymphopenia (ALC ≤200 cells/ml) for HM patients.
排除标准
- •Patient requires mechanical ventilation at time of enrollment
- •Patient is younger than the age of 12 years old
- •The patient is unable to tolerate oral therapy
- •The patient is pregnant at screening ( Positive serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential).
- •The patient is on a prohibited medication. These include Influenza antiviral drugs with the exception of oseltamivir and baloxavir (such as peramivir, laninamivir, zanamivir, rimantadine, umifenovir or amantadine) and herbal therapies.
- •The patient is unable to consent will be excluded
研究组 & 干预措施
Arm I (oseltamivir, baloxavir marboxil)
Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
干预措施: Baloxavir Marboxil (Drug)
Arm I (oseltamivir, baloxavir marboxil)
Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
干预措施: Oseltamivir (Drug)
Arm II (oseltamivir)
Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.
干预措施: Oseltamivir (Drug)
结局指标
主要结局
Changes in viral loads
时间窗: On day 0, 1, 3, 7, 14, and 30
Will be measured via repeat nasopharyngeal swabs at each follow up on day 0, 1, 3, 7, 14 and 30 for influenza quantification.
Incidence of complicated hospital stay
时间窗: Up to 30 days
Defined as a hospital admission that was either prolonged (greater than 7 days), requiring intensive care unit level of care or death at day 30 as a result of influenza infection.
次要结局
- Progression to lower respiratory tract infections(Up to 30 days)
- Rate of resistance to antiviral agents(Up to 30 days)
- Length of hospital stay(Up to 30 days)
- Rate of respiratory failure(Up to 30 days)
- 30-day mortality(At 30 days)
- Changes in microbiome diversity(On day 0, 1, 3, 7, 14, and 30)
- Oxygen requirement(Up to 30 days)