Identifying candidates for early respiratory failure treatment based on Interleukin-6 levels
| ISRCTN | ISRCTN46157068 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN46157068 |
| Secondary identifying numbers | 296418 |
- Submission date
- 07/10/2025
- Registration date
- 09/10/2025
- Last edited
- 09/10/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Acute hypoxemic respiratory failure (AHRF) occurs when the lungs are unable to absorb enough oxygen. The bloodstream is deprived of oxygen which can eventually lead to more severe conditions like multiorgan failure (MOF) and death. AHRF accounts for over 30% of patients to critical care units, so new treatments are sorely needed. Research has shown that blood levels of the inflammatory biomarker Interlukin-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. Identifying patients before their peak IL-6 levels may therefore provide us with a window to administer a new 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.
Who can participate?
Patients aged 18 years and over who arrive at the emergency department with respiratory symptoms and are admitted to inpatient care
What does the study involve?
Patients will have their plasma IL-6 levels measured over 2 days. Patients with elevated IL-6 levels will be randomly allocated into one of three 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.
What are the possible benefits and risks of participating?
Potential benefits to the study include the possibility of improved health outcomes, and contributing to research that may benefit others in the future. Potential risks include the burden undergoing study assessments outside of those needed for standard treatment, and the potential side effects of the study medication.
Where is the study run from?
University Health Network (Canada)
When is the study starting and how long is it expected to run for?
May 2024 to February 2027
Who is funding the study?
UHN AMO Innovation Fund (Canada)
Who is the main contact?
Dominique Abesames, dominiquekate.abesames@uhn.ca
Contact information
Scientific, Principal Investigator
101 College Street
Room 9021
Toronto
M5G 1L7
Canada
| Phone | +1 (0)416 340 3601 |
|---|---|
| lorenzo.delsorbo@uhn.ca |
Principal Investigator
101 College Street
Room 9020
Toronto
M5G 1L7
Canada
| Phone | +1 (0)416 340 3601 |
|---|---|
| martin.urner@uhn.ca |
Public
101 College Street
Room 9028D
Toronto
M5G 1L7
Canada
| Phone | +1 (0)416 340 4800 x6056 |
|---|---|
| dominiquekate.abesames@uhn.ca |
Study information
| Study design | Single-centre Phase II randomized controlled pilot feasibility study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Other, Treatment |
| Scientific title | Interleukin-6 guided treatment with dexamethasone or tocilizumab in patients hospitalized with acute respiratory symptoms - a feasibility study (IDENTIFY) |
| Study acronym | IDENTIFY |
| Study objectives | The hypothesis is that in adult hospital inpatients with acute hypoxemic respiratory failure (AHRF) and elevated interleukin-6 (IL-6) levels, early immunomodulatory treatment with dexamethasone or tocilizumab may reduce progression of disease. This proposed pilot feasibility trial aims to investigate the feasibility of an IL-6 based predictive enrichment strategy to initiate treatment with dexamethasone or tocilizumab in inpatients with respiratory symptoms and elevated IL-6. |
| Ethics approval(s) |
Approved 24/06/2025, University Health Network Research Ethics Board (700 University Ave, 4th Floor, Toronto, ON, M5G 1Z5, Canada; +1 (0)416 581 7849; reb@uhn.ca), ref: 25-5269 |
| Health condition(s) or problem(s) studied | Acute hypoxemic respiratory failure |
| Intervention | Patient's blood IL-6 levels will be measured at 2 timepoints, with samples taken 24-48 hours apart. Patients will be monitored for 28 days, or until discharge from hospital, and data will be gathered from their medical charts. Patients with elevated IL-6 levels will be randomized in a 1:1:1 ratio into one of three study arms. The three study arms are Control, tocilizumab, and dexamethasone. Patients will be randomized via a web-based, allocation-concealed randomization with random block sizes (accessible 24 hours per day). Patients in the control arm will receive on routine care for their specific condition, and no study intervention. Patients in the tocilizumab arm will receive a single intravenous (IV) infusion of tocilizumab, in addition to the routine for their specific condition. Tocilizumab will be infused over 1 hour, at a dosage of 4 mg per kg of body weight, up to a maximum dose of 400 mg. Patients in the dexamethasone arm will receive dexamethasone orally or through an equivalent access, in addition to the routine for their specific condition. Dexamethasone will be given in tablet form at a dosage of 6 mg per day, for up to 10 days. Dexamethasone will be discontinued if the patient is discharged from the hospital. A follow-up interview assessing patient's health-related quality of life will be conducted at 6 months from the end of the 28-day observation period, or hospital discharge (whichever comes first). |
| Intervention type | Mixed |
| Primary outcome measure | 1. Participant recruitment measured using the number of enrolled participants at study closeout. 2. Feasibility of daily IL-6 measurements measured using the number of participants who successfully completed daily IL-6 measurements at study closeout. 3. Proportion of patients meeting eligibility criteria and not randomized measured using number of eligible patients randomized compared to the number of eligible patients not randomized at study closeout. 4. Compliance with the treatment protocol measured using the number of patients who completed the study treatment a outline in the protocol and the amount of associated protocol deviations at study closeout. 5. Time from hospital admission to randomization measured for each randomized patient study closeout. |
| Secondary outcome measures | 1. All-cause 28-day mortality measured at the end of the 28-day observation period. 2. SOFA score increase of greater than or equal to 2, or death over the 28-day observation period. 3. Development of ARDS or death recorded at the end of the 28-day observation period. 4. ICU admission or death recorded at the end of the 28-day observation period. 5. Hospital length of stay recorded at the end of the 28-day observation period. 6. ICU length of stay recorded at the end of the 28-day observation period. 7. Need for invasive mechanical ventilation or death at the end of the 28-day observation period. 8. Duration of invasive mechanical ventilation occurring from the time of enrollment to the end of the 28-day observation period. 9. Health-related quality of life measured using the 36-Item Short Form Survey (SF-36) at 6 months following the 28-day observation period or hospital discharge 10. Survival at 6 months following the 28-day observation period or hospital discharge. 11. Complications of steroids or tocilizumab measured using the number of adverse events of special interest (AESI) related to the study intervention during the 28-day observation period .These AESIs include: 11.1. Hypersensitivity or allergic reaction to tocilizumab 11.2. Nosocomial infections 11.3. Neuromuscular weakness 11.4. Gastrointestinal perforations 11.5. Hypernatremia (serum sodium >150 mmol/L) 11.6. Hyperglycemia (requiring new insulin or increased insulin dose) 11.7. Hepatic dysfunction 11.8. Demyelinating disorders 11.9. Myocardial infarction or acute coronary syndrome 11.10. Malignancies 11.11. Stroke 11.12. New delirium 11.13. Neuromuscular weakness 11.14. Clinically significant gastrointestinal bleeding (requiring transfusion or endoscopy) 11.15. Fetal and infant harm 11.16. Death |
| Overall study start date | 06/05/2024 |
| Completion date | 26/02/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 60 |
| Key inclusion criteria | 1. Age >18 years 2. New onset or worsening of respiratory symptoms (cough, dyspnea, and/or requirement of oxygen supplementation) in the past 14 days 3. Requirement for inpatient hospital management |
| Key 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 >72 h since hospital admission 25. Pregnancy (positive pregnancy test) or breastfeeding (which is a contraindication to tocilizumab) |
| Date of first enrolment | 13/10/2025 |
| Date of final enrolment | 13/10/2026 |
Locations
Countries of recruitment
- Canada
Study participating centre
Toronto
M5G 2C4
Canada
Sponsor information
Other
101 College Street
Room 9021
Toronto
M5G 1L7
Canada
| Website | https://www.uhn.ca |
|---|---|
"ROR" |
https://ror.org/042xt5161 |
Funders
Funder type
Hospital/treatment centre
No information available
No information available
Results and Publications
| Intention to publish date | 13/10/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Editorial Notes
08/10/2025: Study's existence confirmed by the University Health Network Research Ethics Board.
