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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• To determine the potential recruitment rate [Срок оценки: 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 [Срок оценки: Baseline (Day 0) to Day 2]
• To assess the proportion of eligible patients who are not randomized [Срок оценки: Baseline (Day 0) to Day 2]
• To determine the rate of adherence to the assigned treatment strategy and any cross-overs [Срок оценки: 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 [Срок оценки: Baseline to Day 3]

Вторичные конечные точки (11)

• All cause 28-day mortality [Срок оценки: From enrollment to completion of the 28-day observation period (or hospital discharge).]
• Sequential Organ Failure Assessment (SOFA) score increase of ≥2 or death [Срок оценки: From enrollment to end of 28-day observation period (or hospital discharge).]
• Development of ARDS or death [Срок оценки: From enrollment to end of 28-day observation period (or hospital discharge).]
• ICU admission or death [Срок оценки: From enrollment to end of 6-month follow-up period.]
• Hospital length of stay [Срок оценки: From enrollment to end of 28-day observation period (or hospital discharge).]
• ICU length of stay [Срок оценки: From enrollment to end of 28-day observation period (or hospital discharge).]
• Need for invasive mechanical ventilation or death [Срок оценки: From enrollment to end of 28-day observation period (or hospital discharge).]
• Duration of invasive mechanical ventilation [Срок оценки: 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) [Срок оценки: From enrollment to 6 months after the end of 28-day observation period (or hospital discharge)]
• Survival at 6 months [Срок оценки: From enrollment to end of 6-month follow-up period.]
• Complications of steroids or tocilizumab including [Срок оценки: From enrollment to end of 28-day observation period (or hospital discharge).]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Канада · 1 центр

• Toronto General Hospital — Toronto

Идентификаторы

NCT: NCT07334379 · 25-5269 · ISRCTN46157068 · 296418

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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