Interleukin-6 Guided Treatment With Dexamethasone or Tocilizumab in Patients Hospitalized With Acute Respiratory Symptoms - a Feasibility Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- To determine the potential recruitment rate
研究概览
简要总结
Acute hypoxemic respiratory failure (AHRF) happens when the lungs are unable to absorb enough oxygen. The bloodstream is deprived of oxygen which can eventually lead to more severe conditions like multi-organ failure (MOF) and death. AHRF accounts for over 30% of patients to critical care units, thus novel treatments are sorely needed. Research has shown that blood levels of the inflammatory biomarker Interleukin-6 (IL-6) may be a reliable marker for predicting which patients with AHRF will progress into requiring intensive care unit (ICU) admission, MOF, and eventually death. IL-6 levels were shown to reliably peak several days before MOF, ICU admission, and death. Thus, the investigators believe that by identifying patients before the peak of their IL-6 levels, they will be able to administer early treatment to prevent the patient's condition from worsening. The aim of this study is to test the feasibility of a treatment strategy for AHRF based on IL-6 measurement in patients who are admitted to hospital care with AHRF.
Patients who are eligible for the study will have their plasma IL-6 levels measured over 2 days. Patients with elevated IL-6 levels will be randomized into 1 of 3 treatment groups: standard of care only, standard of care plus a single IV infusion of Tocilizumab, or standard of care plus treatment with oral Dexamethasone for 10 days. Patients will then be observed till discharge or up to 28 days, and a follow-up phone interview will be conducted 6 months of the end of the observation period.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Presence of new onset of respiratory symptoms in the previous 14 days upon presentation at the emergency department. Respiratory symptoms are characterized by at least one of the following: cough, dyspnea, or requirement of oxygen supplementation
- •Requirement of inpatient hospital management
排除标准
- •Inability to provide informed consent
- •Patients with known contraindications to dexamethasone or tocilizumab, or any of their components
- •Allergic reaction to tocilizumab or other monoclonal antibodies
- •Patients who are using azathioprine or cyclophosphamide
- •Active tuberculosis infection
- •Patients who have active hepatic disease or hepatic impairment
- •ALT or AST >3x upper limit of normal
- •Neutrophil count <1000/mcl
- •Platelet count <50,000/mm3
- •Hemoglobin (Hb) below 8.5 g/dL,
- •White blood cell count (WBC) below 3000/mm3
- •Absolute Neutrophil Count (ANC) below 2.0 x 109/L
- •absolute lymphocyte count below 500/mm3
- •total bilirubin above ULN
- •Triglycerides (TG) above 10 mmol/L (above 900 mg/dL)
- •Serum creatinine above 1.4 mg/dL in female patients and above 1.6 mg/dL in male patients
- •Patients already receiving systemic steroids, monoclonal antibodies or other immunosuppressive medications at the time of presentation
- •Inability to comply with the regulations to avoid conception within 28 days after enrollment
- •Admission to ICU prior to randomization
- •Immediate need for intubation
- •Imminent death
- •Clinical team refusal
- •Participation in other drug clinical trials (this criterion will be discussed with the PI)
- •Reaching >72h since hospital admission
- •Pregnancy (positive pregnancy test) or breastfeeding (which is a contraindication to tocilizumab)
研究组 & 干预措施
Tocilizumab
Routine care + single intravenous infusion of tocilizumab at a dose of 4mg/kg of body weight (up to a max 400mg).
干预措施: Tocilizumab (Actemra®) (Drug)
Dexamethasone
Routine care + a 10mg of oral dexamethasone per day for up to 10 days (or until hospital discharge).
干预措施: Dexamethasone (Drug)
Control
Routine care only
结局指标
主要结局
To determine the potential recruitment rate
时间窗: From enrollment to completion of the study (in including the 6-month follow-up).
To assess the proportion of eligible patients who do not have daily IL-6 measurement
时间窗: Baseline (Day 0) to Day 2
To assess the proportion of eligible patients who are not randomized
时间窗: Baseline (Day 0) to Day 2
To determine the rate of adherence to the assigned treatment strategy and any cross-overs
时间窗: Baseline to end of 28-day observation period (or hospital discharge)
To estimate the time from hospital admission to randomization and initiation of the allocated treatment
时间窗: Baseline to Day 3
次要结局
- All cause 28-day mortality(From enrollment to completion of the 28-day observation period (or hospital discharge).)
- Sequential Organ Failure Assessment (SOFA) score increase of ≥2 or death(From enrollment to end of 28-day observation period (or hospital discharge).)
- Development of ARDS or death(From enrollment to end of 28-day observation period (or hospital discharge).)
- ICU admission or death(From enrollment to end of 6-month follow-up period.)
- Hospital length of stay(From enrollment to end of 28-day observation period (or hospital discharge).)
- ICU length of stay(From enrollment to end of 28-day observation period (or hospital discharge).)
- Need for invasive mechanical ventilation or death(From enrollment to end of 28-day observation period (or hospital discharge).)
- Duration of invasive mechanical ventilation(From enrollment to end of 28-day observation period (or hospital discharge).)
- Health related quality of life at 6 months assessed using the 36-Item Short Form Survey (SF-36)(From enrollment to 6 months after the end of 28-day observation period (or hospital discharge))
- Survival at 6 months(From enrollment to end of 6-month follow-up period.)
- Complications of steroids or tocilizumab including(From enrollment to end of 28-day observation period (or hospital discharge).)
研究者
Lorenzo delSorbo
MD, Critical Care Medicine Department, Toronto General Hospital
University Health Network, Toronto