A Phase II Single-Center, Randomized, Open-Label, Safety and Efficacy Study of Etoposide in Patients With COVID-19 Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Improvement in Pulmonary Status by Two Categories on an 8 Point Ordinal Scale of Respiratory Function
研究概览
简要总结
This is a randomized, open-label phase II study designed to evaluate the safety and efficacy of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the investigator and treating physician believe the patient had clinical benefit from etoposide therapy but subsequently has evidence of recurrent clinical deterioration. Subjects randomized to control will receive standard of care treatment. No placebo will be used.
详细描述
The rationale for the use of etoposide to treat the cytokine storm in COVID-19 is the high mortality associated with the hyperinflammatory response to the virus, which is similar to that seen in other secondary types of Hemophagocytic lymphohistiocytosis. Autopsy studies of Acute respiratory distress syndrome (ARDS) in COVID patients show a high number of cytolytic T cells in the lungs of such patients. Early autopsy results of COVID patients at Boston Medical Center demonstrate significant hemophagocytosis in lymph nodes and spleen. Comparable studies in the related coronavirus infection severe acute respiratory syndrome (SARS) have demonstrated hemophagocytosis, a hallmark of HLH.15 By targeting the T cells and monocytes driving the cytokine storm in patients with the more severe forms of COVID infection, we hope to alleviate the progression of lung and multi-organ dysfunction characteristic of patients who die from this illness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 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
- •Confirmed COVID-19 infection
- •Evidence of cytokine storm defined as:
- •Peak ferritin > 10,000 ng/mL OR
- •Peak ferritin > 500 ng/mL and one or more of the following at any time during hospital admission: Lactate dehydrogenase > 500 U/L, d-dimer >1000 ng/mL, C-reactive protein > 100 mg/L, or white blood count> 15 k/microlitre
- •Cohort 1: Intubated status as a result of COVID infection-associated respiratory illness.
排除标准
- •Pregnancy or breastfeeding
- •History of severe hypersensitivity to etoposide products
- •Absolute neutrophil count (ANC) < 1000 cells/mm3
- •Platelet count <50,000/mm3
- •Bilirubin > 3.0 mg/dL
- •Aspartate OR alanine aminotransferase > 5.0 x upper limit of normal
- •Creatinine Clearance < 15 mL/min (calculated by Cockcroft Fault formula)
- •Requiring continuous renal replacement therapy
- •Requiring >1 vasopressor
- •Requiring extracorporeal membrane oxygenation (ECMO)
- •Other active, life-threatening infections
- •Anti-cytokine treatment (including anakinra or Interleukin 6 antibodies eg tocilizumab, sarilumab) administration within three half-lives of the medication used
- •Hydroxychloroquine, colchicine, azithromycin, doxycycline-if administered for COVID infection-must be discontinued for at least 24 hours prior to randomization.
- •Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with subject participation, or is not in the best interest of the patient to participate, in the opinion of the investigator.
- •Inability to consent and no legally authorized representative
- •Poorly controlled HIV infection (CD4 count <100 cells/mm3)
研究组 & 干预措施
Cohort 1 - Etoposide
Participants that are on ventilation Etoposide 150 mg/m2 daily days 1 and 4
干预措施: Etoposide (Drug)
结局指标
主要结局
Improvement in Pulmonary Status by Two Categories on an 8 Point Ordinal Scale of Respiratory Function
时间窗: baseline, through hospital discharge or death
8-Point Ordinal Scale of Respiratory Function: 8 -Death; 7 -Ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT), or need for vasopressors (dopamine ≥5 μg/kg/min OR epinephrine ≥0.1 μg/kg/min OR norepinephrine ≥0.1 μg/kg/min) 6 -Intubation and mechanical ventilation 5 -Non-invasive mechanical ventilation (NIV) or high-flow oxygen 4 -Hospitalized, requiring oxygen by mask or nasal prongs 3 -Hospitalization without oxygen supplementation 2-Discharged from hospital either to home with supplemental oxygen OR to inpatient rehabilitation/skilled nursing facility(+/-supplemental oxygen); 1 -Discharged to home without supplemental oxygen
次要结局
- Overall Survival(30 Days)
- Change in Blood Ferritin Levels(baseline, to day 30 (or discharge or death))
- Duration of Ventilation After Treatment(From date of enrollment until the date of extubation)
- Change in C-reactive Protein (CRP) Levels(baseline, to day 30 (or discharge or death))
- Change in D-dimer Blood Levels(baseline, to day 30 (or discharge or death))
- Change in Platelet Count(baseline, to day 30 (or discharge or death))
- Length of Hospitalization(From date of enrollment until date of discharge)
- Change in White Blood Cell Count(baseline, to day 30 (or discharge or death))
研究者
John Mark Sloan
Principal Investigator
Boston Medical Center