Clinical trial NCT05914454: Efficacy and Safety of Anakinra in Acute Respiratory Distress Syndrome
Official title: Efficacy and Safety of Anakinra in Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
Keywords: IL-1
anakinra
acute respiratory distress syndrome
lung
Lead sponsor: Azienda Sanitaria-Universitaria Integrata di Udine
Sponsor class: OTHER
Collaborators: name: University of Udine
First posted: 2023-06-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of ventilation-free days
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria
Study officials:
affiliation: Azienda Sanitaria Universitaria Friuli Centrale
name: Tiziana Bove, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: