Efficacy and Safety of Anakinra in Acute Respiratory Distress Syndrome (ESKA)

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterized by acute respiratory failure with hypoxemia, noncardiogenic or non-fluid overload pulmonary edema, bilateral diffuse opacities on chest radiograph in the presence of a predisposing factor.

In ARDS there is activation of the inflammatory cascade which is very intense and persistent in the severe types. It was highlighted that the inflammatory cytokines in patients with ARDS or sepsis is similar to that observed in COVID-19 positive patients.

Emerging therapies include immunomodulation and the administration of mesenchymal stem cells for the modulation of lung repair through the release of cytokines and growth factors that modulate the local inflammatory response.

Regardless of the cause of ARDS, the severity of the inflammatory state and fibroproliferative evolution have been shown to be independent predictors of survival and ventilator dependence. Patients suffering from severe forms of ARDS in fact require prolonged mechanical ventilation, which exposes them to ventilator-associated pneumonia (VAP) and the onset of multiorgan insufficiency. The hyperinflammatory state underlying ARDS predisposes to pulmonary fibroproliferation, which in turn increases susceptibility to ventilator dependence and increases the risk of MOF and death. For this reason, the rationale in the use of anakinra is to limit the inflammatory process of ARDS as early as possible, avoiding the progression of lung damage.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Anakinra 100Mg/0.67Ml Inj Syringe

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tiziana Bove, MD, PhD; Phone Number: +39 0432559501; Email: tiziana.bove@asufc.sanita.fvg.it
• Study Contact Backup: Name: Luca Quartuccio, MD, PhD; Phone Number: +39 3487040396; Email: luca.quartuccio@asufc.sanita.fvg.it

Study Locations

• Italy
  • Udine, Italy, 33100
    • Recruiting
    • Azienda Sanitaria Universitaria
    • Contact: Tiziana Quartuccio, MD, PhD; Phone Number: +39 0432559501; Email: tiziana.bove@asufc.sanita.fvg.it
    • Sub-Investigator: Luca Quartuccio, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients admitted to intensive care unit diagnosed within 48 hours of moderate-severe ARDS (PaO2/FiO2 < 200, PEEP ≥ 5 cmH2O) and requiring intubation and mechanical ventilation;
• Berlin clinical criteria for definition of ARDS: onset within 1 week of initial lesion or new or worsening respiratory symptoms, bilateral opacities not fully explained by effusions, lobar or lung collapse or nodules, respiratory failure not fully explained by heart failure or fluid overload

• ARDS-like clinical-laboratory profile, defined by at least one of the following criteria:

  • high plasma levels of inflammatory biomarkers (e.g. IL-6 > 80 pg/ml, CRP > 250 mg/l)
  • dependence on vasopressors (of any type and at any dosage for at least one hour of treatment)
  • reduction of bicarbonatemia (< 18 mMol/L) or hyperlactacidemia (> 4 mMol/L)
• Informed consent for participation in the study
• Negative swab for COVID-19.

Exclusion Criteria:

• Pregnant or lactating patients;
• Hypersensitivity to the active substance or to any of the excipients or to proteins derived from Escherichia Coli;
• Concomitant treatment with anti-TNF-alpha or other biotechnological agent;
• Neutropenia (neutrophils < 1.5 x 109/L);
• Pre-existing malignancies;
• Moderate to severe renal insufficiency, creatinine clearance < 60 ml/minute.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: standard of care
Experimental: anakinra; anakinra 100 mg/day for 14 consecutive days	Drug: Anakinra 100Mg/0.67Ml Inj Syringe; anakinra 100 mg per day for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of ventilation-free days	The calculation will take place from the day of extubation to the 28th day of hospitalization. Patients who die before ventilator weaning will be considered as having 0 days off ventilation. The calculation of the days free from ventilation will be calculated as follows: 28 - number of days of ventilation.	28 days

Collaborators and Investigators

• Sponsor: Azienda Sanitaria-Universitaria Integrata di Udine
• Collaborators: University of Udine
• Investigators: Principal Investigator: Tiziana Bove, MD, PhD, ASUFC

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Estimated): June 19, 2025
• Study Completion (Estimated): September 19, 2025

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: lung; anakinra; acute respiratory distress syndrome; IL-1
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 4381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No