Acute Hypoxemic Respiratory Failure
Conditions
Brief summary
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.
Interventions
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.
DRUGDexamethasone
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.
Sponsors
Roche Diagnostic Ltd.
Lorenzo delSorbo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
This study is a pilot, feasibility study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. 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 3. Requirement of inpatient hospital management
Exclusion criteria
1. Inability to provide informed consent 2. Patients with known contraindications to dexamethasone or tocilizumab, or any of their components 3. Allergic reaction to tocilizumab or other monoclonal antibodies 4. Patients who are using azathioprine or cyclophosphamide 5. Active tuberculosis infection 6. Patients who have active hepatic disease or hepatic impairment 7. ALT or AST \>3x upper limit of normal 8. Neutrophil count \<1000/mcl 9. Platelet count \<50,000/mm3 10. Hemoglobin (Hb) below 8.5 g/dL, 11. White blood cell count (WBC) below 3000/mm3 12. Absolute Neutrophil Count (ANC) below 2.0 x 109/L 13. absolute lymphocyte count below 500/mm3 14. total bilirubin above ULN 15. Triglycerides (TG) above 10 mmol/L (above 900 mg/dL) 16. Serum creatinine above 1.4 mg/dL in female patients and above 1.6 mg/dL in male patients 17. Patients already receiving systemic steroids, monoclonal antibodies or other immunosuppressive medications at the time of presentation 18. Inability to comply with the regulations to avoid conception within 28 days after enrollment 19. Admission to ICU prior to randomization 20. Immediate need for intubation 21. Imminent death 22. Clinical team refusal 23. Participation in other drug clinical trials (this criterion will be discussed with the PI) 24. Reaching \>72h since hospital admission 25. Pregnancy (positive pregnancy test) or breastfeeding (which is a contraindication to tocilizumab)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To estimate the time from hospital admission to randomization and initiation of the allocated treatment | Baseline to Day 3 |
| To determine the potential recruitment rate | 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 | Baseline (Day 0) to Day 2 |
| To assess the proportion of eligible patients who are not randomized | Baseline (Day 0) to Day 2 |
| To determine the rate of adherence to the assigned treatment strategy and any cross-overs | Baseline to end of 28-day observation period (or hospital discharge) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | — |
| 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) | 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. |
| 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). | 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 |
| Duration of invasive mechanical ventilation | From enrollment to end of 28-day observation period (or hospital discharge). | — |
| 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). | 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 | 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. | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| To assess reasons why eligible patients are not randomized | Baseline (Day 0) to Day 2. | 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. |
Countries
Canada
Outcome results
None listed