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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
60
Subjects randomized to the tocilizumab arm will receive a single intravenous (IV) infusion of tocilizumab, given over 1 hour. The tocilizumab will be given at a dosage of 4mg per kg of body weight, up to a maximum dose of 400 mg.
Subjects randomized to the dexamethasone arm will receive 6 mg of dexamethasone per day, for up to 10 days, or until discharged from the hospital. Dexamethasone will be given in tablet form orally (by mouth) or through an equivalent method.
Toronto General Hospital
Toronto, Ontario, Canada
RECRUITINGTo determine the potential recruitment rate
Time frame: 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
Time frame: Baseline (Day 0) to Day 2
To assess the proportion of eligible patients who are not randomized
Time frame: Baseline (Day 0) to Day 2
To determine the rate of adherence to the assigned treatment strategy and any cross-overs
Time frame: 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
Time frame: Baseline to Day 3
All cause 28-day mortality
Time frame: From enrollment to completion of the 28-day observation period (or hospital discharge).
Sequential Organ Failure Assessment (SOFA) score increase of ≥2 or death
The SOFA (Sequential Organ Failure Assessment) scale is used to assess a patient's organ function. The SOFA score is based on 6 different systems: respiratory, cardiovascular, hepatic, coagulation, renal, and neurological. Each system is given a score from 0 (best) to 4 (worst). Total SOFA score is calculated by adding the scores for each system, with a lower total SOFA scores generally denote better overall organ function.
Time frame: From enrollment to end of 28-day observation period (or hospital discharge).
Development of ARDS or death
Time frame: From enrollment to end of 28-day observation period (or hospital discharge).
ICU admission or death
Time frame: From enrollment to end of 6-month follow-up period.
Hospital length of stay
Time frame: From enrollment to end of 28-day observation period (or hospital discharge).
ICU length of stay
Time frame: From enrollment to end of 28-day observation period (or hospital discharge).
Need for invasive mechanical ventilation or death
Time frame: From enrollment to end of 28-day observation period (or hospital discharge).
Duration of invasive mechanical ventilation
Time frame: 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)
The SF-36 is a 36-item survey that scores patients on eight health scales: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. The SF-36 is structured so higher scores on each scale generally denote a more favorable health outcome. It also includes a single item that provides an indication of perceived change in health.
Time frame: From enrollment to 6 months after the end of 28-day observation period (or hospital discharge)
Survival at 6 months
Time frame: From enrollment to end of 6-month follow-up period.
Complications of steroids or tocilizumab including
Complications including: Hypersensitivity or allergic reaction to tocilizumab, Nosocomial infections, Neuromuscular weakness, Gastrointestinal perforations.=, Hypernatremia (serum sodium \>150 mmol/L), Hyperglycemia (requiring new insulin or increased insulin dose), Hepatic dysfunction, Demyelinating disorders, Myocardial infarction or acute coronary syndrome, Malignancies, Stroke, New delirium, Neuromuscular weakness, Clinically significant gastrointestinal bleeding (requiring transfusion or endoscopy), Fetal and infant harm, and Death
Time frame: From enrollment to end of 28-day observation period (or hospital discharge).
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