ESKA: Efficacy and Safety of Anakinra in Acute Respiratory Distress Syndrome

Sponsor

Azienda Sanitaria-Universitaria Integrata di Udine (Other)

Overall Status

Recruiting

CT.gov ID

NCT05914454

Collaborator

University of Udine (Other)

Enrollment

Location

Arms

28.1

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome	Drug: Anakinra 100Mg/0.67Ml Inj Syringe	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Anakinra in Acute Respiratory Distress Syndrome

Actual Study Start Date :

May 19, 2023

Anticipated Primary Completion Date :

Jun 19, 2025

Anticipated Study Completion Date :

Sep 19, 2025

Arms and Interventions

Arm	Intervention/Treatment
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
No Intervention: standard of care

Arm

Intervention/Treatment

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

No Intervention: standard of care

Outcome Measures

Primary Outcome Measures

Assessment of ventilation-free days [28 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.