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Recruiting NCT07334379

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

Phase II Interventional Acute Hypoxemic Respiratory Failure

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Tocilizumab (Actemra®), Dexamethasone.
Who it may be relevant to
Registry conditions: Acute Hypoxemic Respiratory Failure. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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

  • Drug Tocilizumab (Actemra®)
    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.
  • Drug Dexamethasone
    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.

Primary outcome measures

  • To 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]
Secondary outcome measures (11)
  • 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 [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) [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 [Time frame: From enrollment to end of 28-day observation period (or hospital discharge).]

Eligibility criteria

Inclusion criteria

  • 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

Exclusion criteria

  • Inability to provide informed consent
  • Patients with known contraindications to dexamethasone or tocilizumab, or any of their components
  • Allergic reaction to tocilizumab or other monoclonal antibodies
  • Patients who are using azathioprine or cyclophosphamide
  • Active tuberculosis infection
  • Patients who have active hepatic disease or hepatic impairment
  • ALT or AST >3x upper limit of normal
  • Neutrophil count <1000/mcl
  • Platelet count <50,000/mm3
  • Hemoglobin (Hb) below 8.5 g/dL,
  • White blood cell count (WBC) below 3000/mm3
  • Absolute Neutrophil Count (ANC) below 2.0 x 109/L
  • absolute lymphocyte count below 500/mm3
  • total bilirubin above ULN
  • Triglycerides (TG) above 10 mmol/L (above 900 mg/dL)
  • Serum creatinine above 1.4 mg/dL in female patients and above 1.6 mg/dL in male patients
  • Patients already receiving systemic steroids, monoclonal antibodies or other immunosuppressive medications at the time of presentation
  • Inability to comply with the regulations to avoid conception within 28 days after enrollment
  • Admission to ICU prior to randomization
  • Immediate need for intubation
  • Imminent death
  • Clinical team refusal
  • Participation in other drug clinical trials (this criterion will be discussed with the PI)
  • Reaching >72h since hospital admission
  • Pregnancy (positive pregnancy test) or breastfeeding (which is a contraindication to tocilizumab)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Other

Study locations

Canada · 1 center
  • Toronto General Hospital — Toronto

Identifiers

NCT: NCT07334379 · 25-5269 · ISRCTN46157068 · 296418

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗