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

(ARDS caused by Non-COVID-19 cohort)

Inclusion Criteria:

At Informed Consent

1. Patients with ARDS confirmed by the Berlin definition based on the followingdiagnostic criteria (a)-(d):

2. Patients within 7 days from invasion or exacerbation of respiratory symptoms oracute onset of ARDS.

3. Patients with respiratory failure not fully explained by cardiac failure orfluid overload; Need objective assessment (e. g., echo-cardiography) to excludehydrostatic edema if no risk factor present

4. Patients with bilateral opacities not fully explained by effusions, lobar/ lungcollapse, or nodules on chest X-ray or CT scan

5. Patients with PaO2/ FiO2 ratio ≤ 300 mmHg (PEEP ≥ 5 cmH2O)

6. Patients who are intubated and mechanically ventilated

7. Patients who can be enrolled in the study within 96 hours after initiation ofmechanical ventilation

8. Patients aged ≥ 16 years at informed consent (Signed informed consent form fromlegally acceptable representative must be available if patient is aged < 20 years)

At Enrollment

1. Patients with PaO2/ FiO2 ratio ≥ 50 mmHg and ≤ 200 mmHg (PEEP ≥ 5 cmH2O)

2. Patients with bilateral opacities not fully explained by effusions, lobar/ lungcollapse, or nodules on CT scan within 48 hours before enrollment

3. Patients who are intubated and mechanically ventilated

4. Patients who can be enrolled in the study within 96 hours after initiation ofmechanical ventilation

Exclusion Criteria:

At Informed Consent

1. Patients who are considered to be extremely unlikely to withdraw from mechanicalventilation

2. Patients who are treated with ECMO or HFOV

3. Patients with renal dialysis therapy for chronic renal failure

4. Patients with congestive heart failure (NYHA class IV)

5. Patients with acuter left ventricular failure

6. Patients with liver failure (Child-Pugh grade C)

7. Patients who have burns in excess of 15% total body surface area

8. Patients after resuscitation from cardiac arrest

9. Patients with a history of hypersensitivity to the anticoagulants (Heparin orNafamostat mesylate)

10. Patients who have received cytapheresis, blood purification therapy with cytokineadsorbing devices or endotoxin removal therapy within 7 days prior to informedconsent

11. Patients with pregnancy or lactating

12. Patients tested positive for COVID-19

At Enrollment

1. Patients who are considered to be extremely unlikely to withdraw from mechanicalventilation

2. Patients who are treated with ECMO or HFOV after obtaining informed consent prior toenrollment

3. Patients with platelet count ≤ 50,000 /mm3 by the latest blood test

4. Patients who have received cytapheresis, blood purification therapy with cytokineadsorbing devices or endotoxin removal therapy between informed consent andenrollment

5. Patients whose life expectancy is ≤ 24 hours after enrollment

6. Patients after resuscitation from cardiac arrest between informed consent andenrollment

7. Patients tested positive for COVID-19 between informed consent and enrollment

(ARDS caused by COVID-19 cohort)

Inclusion Criteria:

At Informed Consent

1. Patients tested positive for COVID-19

2. Patients with ARDS confirmed by the Berlin definition based on the followingdiagnostic criteria (a)-(d):

3. Patients within 7 days from invasion or exacerbation of respiratory symptoms oracute onset of ARDS.

4. Patients with respiratory failure not fully explained by cardiac failure orfluid overload; Need objective assessment (e. g., echo-cardiography) to excludehydrostatic edema if no risk factor present

5. Patients with bilateral opacities not fully explained by effusions, lobar/ lungcollapse, or nodules on chest X-ray or CT scan

6. Patients with PaO2/ FiO2 ratio ≤ 300 mmHg (PEEP ≥ 5 cmH2O)

7. Patients who are intubated and mechanically ventilated

8. Patients who can be enrolled in the study within 96 hours after initiation ofmechanical ventilation

9. Patients aged ≥ 16 years at informed consent (Signed informed consent form fromlegally acceptable representative must be available if patient is aged < 20 years)

At Enrollment

1. Patients with PaO2/ FiO2 ratio ≥ 50 mmHg and ≤ 200 mmHg (PEEP ≥ 5 cmH2O)

2. Patients who are intubated and mechanically ventilated

3. Patients who can be enrolled in the study within 96 hours after initiation ofmechanical ventilation

Exclusion Criteria:

At Informed Consent

1. Patients who are considered to be extremely unlikely to withdraw from mechanicalventilation

2. Patients who are treated with ECMO or HFOV

3. Patients with renal dialysis therapy for chronic renal failure

4. Patients with congestive heart failure (NYHA class IV)

5. Patients with acuter left ventricular failure

6. Patients with liver failure (Child-Pugh grade C)

7. Patients who have burns in excess of 15% total body surface area

8. Patients after resuscitation from cardiac arrest

9. Patients with a history of hypersensitivity to the anticoagulants (Heparin orNafamostat mesylate)

10. Patients who have received cytapheresis, blood purification therapy with cytokineadsorbing devices or endotoxin removal therapy within 7 days prior to informedconsent

11. Patients with pregnancy or lactating

At Enrollment

1. Patients who are considered to be extremely unlikely to withdraw from mechanicalventilation

2. Patients who are treated with ECMO or HFOV after obtaining informed consent prior toenrollment

3. Patients with platelet count ≤ 50,000 /mm3 by the latest blood test

4. Patients who have received cytapheresis, blood purification therapy with cytokineadsorbing devices or endotoxin removal therapy between informed consent andenrollment

5. Patients whose life expectancy is ≤ 24 hours after enrollment

6. Patients after resuscitation from cardiac arrest between informed consent andenrollment