Interleukin-6 Guided Treatment With Dexamethasone or Tocilizumab in Patients Hospitalized With Acute Respiratory Symptoms - a Feasibility Study (IDENTIFY)

Lorenzo delSorbo

Status and phase: Enrolling; Phase 2

Conditions: Acute Hypoxemic Respiratory Failure

Treatments: Drug: Tocilizumab (Actemra®); Drug: Dexamethasone

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07334379

296418 (Other Identifier)

25-5269

ISRCTN46157068 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Control

No Intervention group

Description:

Routine care only

Tocilizumab

Experimental group

Description:

Routine care + single intravenous infusion of tocilizumab at a dose of 4mg/kg of body weight (up to a max 400mg).

Treatment:

Drug: Tocilizumab (Actemra®)

Dexamethasone

Experimental group

Description:

Routine care + a 10mg of oral dexamethasone per day for up to 10 days (or until hospital discharge).

Treatment:

Drug: Dexamethasone