Early Institution of Tocilizumab Titration in Non-Critical Hospitalized COVID-19 Pneumonitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinical Response in Maximum Temperature (Tmax)
研究概览
简要总结
Coronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose.
Hypotheses:
- Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death.
- Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death.
Objectives:
- To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
- To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Adults ≥ 18 years of age
- •Approval from the patient's primary service
- •Admitted as an inpatient to University of Chicago Medicine
- •Fever, documented in electronic medical record and defined as: T ≥ 38*C by any conventional clinical method (forehead, tympanic, oral, axillary, rectal)
- •Positive test for active SARS-CoV-2 infection
- •Radiographic evidence of infiltrates on chest radiograph (CXR) or computed tomography (CT)
- •Ability to provide written informed consent on the part of the subject or, in the absence of decisional capacity of the subject, an appropriate surrogate (e.g. a legally authorized representative).
排除标准
- •Concurrent use of invasive mechanical ventilation (patients receiving non-invasive mechanical ventilation [CPAP, BiPap, HHFNC] are eligible)
- •Concurrent use of vasopressor or inotropic medications
- •Previous receipt of tocilizumab or another anti-IL6R or IL-6 inhibitor.
- •Known history of hypersensitivity to tocilizumab.
- •Patients who are actively being considered for a study of an antiviral agent that would potentially exclude concurrent enrollment on this study.
- •Patients actively receiving an investigational antiviral agent in the context of a clinical research study.
- •Diagnosis of end-stage liver disease or listed for liver transplant.
- •Elevation of AST or ALT in excess of 5 times the upper limit of normal.
- •Neutropenia (Absolute neutrophil count < 500/uL).
- •Thrombocytopenia (Platelets < 50,000/uL).
- •On active therapy with a biologic immunosuppressive agent, which include the following biologics and any biosimilar versions thereof:
- •Alemtuzumab
- •Blinatumomab
- •Brentuximab
- •Daratumumab
- •Elotuzumab
- •Ibritumomab
- •Obinutuzumab
- •Ofatumumab
- •Ocrelizumab
- •Rituximab
- •Inotuzumab
- •Gemtuzumab
- •Tositumumab
- •Moxetumomab
- •Polatuzumab
- •Abatacept
- •Adalimumab
- •Belimumab
- •Certolizumab
- •Eculizumab
- •Etanercept
- •Golimumab
- •Infliximab
- •Ixekizumab
- •Rituximab
- •Sarilumab
- •Secukinumab
- •Tocilizumab
- •Ustekinumab
- •On active therapy with a JAK2-targeted agent, which include the following:
- •Tofacitinib
- •Baricitinib
- •Upadacitinib
- •Ruxolitinib
- •History of bone marrow transplantation or solid organ transplant.
- •Known history of Hepatitis B or Hepatitis C.
- •Known history of mycobacterium tuberculosis infection at risk for reactivation.
- •Known history of gastrointestinal perforation or active diverticulitis.
- •Multi-organ failure as determined by primary treating team
- 另有 27 项未显示
研究组 & 干预措施
Group A
Hospitalized, non-critically ill patients with COVID-19 pneumonitis with risk factors for decompensation
干预措施: Tocilizumab (Drug)
Group B
Hospitalized, non-critically ill patients with COVID-19 pneumonitis without risk factors for decompensation
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Number of Participants With Clinical Response in Maximum Temperature (Tmax)
时间窗: Assessed for the 24 hour period after tocilizumab administration
Number of Participants with Clinical Response in Maximum Temperature (Tmax)
Number of Participants With Biochemical Response as Determined by CRP Response
时间窗: Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administration
Number of Participants with Biochemical Response as determined by CRP Response. Defined as at least 25% decrease in CRP from baseline at least 16 hours after administration of drug.
次要结局
- Duration of Mechanical Ventilation(Hospitalization, up to 4 weeks after tocilizumab administration)
- Time to Mechanical Ventilation(Assessed over hospitalization, up to 4 weeks after tocilizumab administration)
- Progression of COVID-19 Pneumonitis(Hospitalization, up to 4 weeks after tocilizumab administration)
- Rate of Vasopressor/Inotrope Utilization(Hospitalization, up to 4 weeks after tocilizumab administration)
- Overall Survival(28 days)
- Survival to Hospital Discharge(Hospitalization, up to 4 weeks after tocilizumab administration)
- Duration of Increased Supplemental Oxygen Requirement From Baseline(Assessed over hospitalization, up to 4 weeks after tocilizumab administration)
- Time to Vasopressor or Inotropic Utilization(Assessed over hospitalization, up to 4 weeks after tocilizumab administration)
- Number of ICU Days(Hospitalization, up to 4 weeks after tocilizumab administration)
- Rate of Non-elective Mechanical Ventilation(Hospitalization, up to 4 weeks after tocilizumab administration)
- Duration of Vasopressor/Inotrope Utilization(Hospitalization, up to 4 weeks after tocilizumab administration)