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.
This study has two phases: 1) observational and 2) interventional.
In the observational phase 1, patients who meet the inclusion and a general exclusion criteria are eligible for participation. In the observational phase, patients will have their plasma IL-6 levels measured over 2 days. Patients' clinical condition will be observed till discharge or up to 28 days of admission, and data will be collected from their medical charts.
Patients participating in the observational phase 1 will be considered eligible to join the interventional phase 2 if: they are found to have elevated IL-6 levels, and they meet additional randomization exclusion criteria. In the interventional phase, patients 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' clinical condition will be observed till discharge or up to 28 days of admission, and data will be collected from their medical charts. A follow-up phone interview will be conducted 6 months of the end of the observation period.
Patients participating in the observational phase 1 who are not eligible to participate in the interventional phase 2 will continue in the observational phase 1 only. These patients will not be randomized to a group, receive any study medications, or be contacted for the 6-month follow-up.
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
Inability to provide informed consent
Immediate need for admission to ICU
Immediate need for intubation
Imminent death
Parallel
Tocilizumab (Actemra®)
DrugSubjects 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.
Dexamethasone
DrugSubjects 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.
To determine the potential recruitment rate
To assess the proportion of eligible patients who do not have daily IL-6 measurement
To assess the proportion of eligible patients who are not randomized
To determine the rate of adherence to the assigned treatment strategy and any cross-overs
All cause 28-day mortality
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.
Development of ARDS or death
ICU admission or death
To assess reasons why eligible patients are not randomized
In addition to primary outcome #3: To assess the proportion of eligible patients who are not randomized, the reasons why eligible patients are not randomized will also be recorded.
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Lorenzo delSorbo
Lead sponsor
University Health Network, Toronto
Sponsor institution
Roche Diagnostic Ltd.
Collaborator
