Pilot Clinical Study of NOA-001 for ARDS (Acute Respiratory Distress Syndrome)

(ARDS caused by Non-COVID-19 cohort): The objectives of this clinical study is to investigate the efficacy and safety of NOA-001 in patients with ARDS caused by Non-COVID-19. The number of patients enrolled is 30 (20 patients in the NOA-001 group and 10 patients in the standard therapy group).

(ARDS caused by COVID-19 cohort): The objectives of this clinical study is to investigate the efficacy and the safety of NOA-001 in patients with ARDS caused by COVID-19. The number of patients enrolled is 15 (in the NOA-001 group only).

(ARDS caused by Non-COVID-19 cohort)

Inclusion criteria

At Informed Consent

• Patients with ARDS confirmed by the Berlin definition based on the following diagnostic criteria (a)-(d):

• Patients within 7 days from invasion or exacerbation of respiratory symptoms or acute onset of ARDS.
• Patients with respiratory failure not fully explained by cardiac failure or fluid overload; Need objective assessment (e. g., echo-cardiography) to exclude hydrostatic edema if no risk factor present
• Patients with bilateral opacities not fully explained by effusions, lobar/ lung collapse, or nodules on chest X-ray or CT scan
• Patients with PaO2/ FiO2 ratio ≤ 300 mmHg (PEEP ≥ 5 cmH2O)
• Patients who are intubated and mechanically ventilated
• Patients who can be enrolled in the study within 96 hours after initiation of mechanical ventilation
• Patients aged ≥ 16 years at informed consent (Signed informed consent form from legally acceptable representative must be available if patient is aged < 20 years)

At Enrollment

• Patients with PaO2/ FiO2 ratio ≥ 50 mmHg and ≤ 200 mmHg (PEEP ≥ 5 cmH2O)
• Patients with bilateral opacities not fully explained by effusions, lobar/ lung collapse, or nodules on CT scan within 48 hours before enrollment
• Patients who are intubated and mechanically ventilated
• Patients who can be enrolled in the study within 96 hours after initiation of mechanical ventilation

Exclusion criteria

At Informed Consent

• Patients who are considered to be extremely unlikely to withdraw from mechanical ventilation
• Patients who are treated with ECMO or HFOV
• Patients with renal dialysis therapy for chronic renal failure
• Patients with congestive heart failure (NYHA class IV)
• Patients with acuter left ventricular failure
• Patients with liver failure (Child-Pugh grade C)
• Patients who have burns in excess of 15% total body surface area
• Patients after resuscitation from cardiac arrest
• Patients with a history of hypersensitivity to the anticoagulants (Heparin or Nafamostat mesylate)
• Patients who have received cytapheresis, blood purification therapy with cytokine adsorbing devices or endotoxin removal therapy within 7 days prior to informed consent
• Patients with pregnancy or lactating
• Patients tested positive for COVID-19

At Enrollment

• Patients who are considered to be extremely unlikely to withdraw from mechanical ventilation
• Patients who are treated with ECMO or HFOV after obtaining informed consent prior to enrollment
• Patients with platelet count ≤ 50,000 /mm3 by the latest blood test
• Patients who have received cytapheresis, blood purification therapy with cytokine adsorbing devices or endotoxin removal therapy between informed consent and enrollment
• Patients whose life expectancy is ≤ 24 hours after enrollment
• Patients after resuscitation from cardiac arrest between informed consent and enrollment
• Patients tested positive for COVID-19 between informed consent and enrollment

(ARDS caused by COVID-19 cohort)

Inclusion criteria

At Informed Consent

• Patients tested positive for COVID-19
• Patients with ARDS confirmed by the Berlin definition based on the following diagnostic criteria (a)-(d):

• Patients within 7 days from invasion or exacerbation of respiratory symptoms or acute onset of ARDS.
• Patients with respiratory failure not fully explained by cardiac failure or fluid overload; Need objective assessment (e. g., echo-cardiography) to exclude hydrostatic edema if no risk factor present
• Patients with bilateral opacities not fully explained by effusions, lobar/ lung collapse, or nodules on chest X-ray or CT scan
• Patients with PaO2/ FiO2 ratio ≤ 300 mmHg (PEEP ≥ 5 cmH2O)
• Patients who are intubated and mechanically ventilated
• Patients who can be enrolled in the study within 96 hours after initiation of mechanical ventilation
• Patients aged ≥ 16 years at informed consent (Signed informed consent form from legally acceptable representative must be available if patient is aged < 20 years)

At Enrollment

• Patients with PaO2/ FiO2 ratio ≥ 50 mmHg and ≤ 200 mmHg (PEEP ≥ 5 cmH2O)
• Patients who are intubated and mechanically ventilated
• Patients who can be enrolled in the study within 96 hours after initiation of mechanical ventilation

Exclusion criteria

At Informed Consent

• Patients who are considered to be extremely unlikely to withdraw from mechanical ventilation
• Patients who are treated with ECMO or HFOV
• Patients with renal dialysis therapy for chronic renal failure
• Patients with congestive heart failure (NYHA class IV)
• Patients with acuter left ventricular failure
• Patients with liver failure (Child-Pugh grade C)
• Patients who have burns in excess of 15% total body surface area
• Patients after resuscitation from cardiac arrest
• Patients with a history of hypersensitivity to the anticoagulants (Heparin or Nafamostat mesylate)
• Patients who have received cytapheresis, blood purification therapy with cytokine adsorbing devices or endotoxin removal therapy within 7 days prior to informed consent
• Patients with pregnancy or lactating

At Enrollment

• Patients who are considered to be extremely unlikely to withdraw from mechanical ventilation
• Patients who are treated with ECMO or HFOV after obtaining informed consent prior to enrollment
• Patients with platelet count ≤ 50,000 /mm3 by the latest blood test
• Patients who have received cytapheresis, blood purification therapy with cytokine adsorbing devices or endotoxin removal therapy between informed consent and enrollment
• Patients whose life expectancy is ≤ 24 hours after enrollment
• Patients after resuscitation from cardiac arrest between informed consent and enrollment