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

Study Overview
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Brief Summary
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The primary object of this clinical study is to investigate the efficacy and the safety of NOA-001 in patients with ARDS (ARDS caused by Non-COVID-19 or COVID-19).

Detailed Description
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(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).

Official Title
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Pilot Clinical Study to Investigate the Efficacy and Safety of NOA-001 for the Treatment of Patients With Acute Respiratory Distress Syndrome.

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Device: NOA-001


Participation Criteria
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Eligibility Criteria
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(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 48 hours after ARDS diagnosis confirmed by Berlin definition 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 48 hours after ARDS diagnosis confirmed by Berlin definition Exclusion Criteria: At Informed Consent Patients with mechanical ventilation for more than 48 hours prior to ARDS diagnosis confirmed by Berlin definition 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 48 hours after ARDS diagnosis confirmed by Berlin definition 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 48 hours after ARDS diagnosis confirmed by Berlin definition Exclusion Criteria: At Informed Consent Patients with mechanical ventilation for more than 48 hours prior to ARDS diagnosis confirmed by Berlin definition 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOA-001 group (ARDS caused by Non-COVID-19 cohort)<br>Patients will receive the standard and NOA-001 therapy. | Device: NOA-001<br>* NOA-001 will be replaced regularly (at 22 to 24 hours after the initiation of procedure), and will be continuously performed until 168 hours from the enrollment.<br>|
| No Intervention: Standard treatment group (ARDS caused by Non-COVID-19 cohort)<br>Patients will receive the standard therapy. | |
| Experimental: NOA-001 group (ARDS caused by COVID-19 cohort)<br>Patients will receive the standard and NOA-001 therapy. | Device: NOA-001<br>* NOA-001 will be replaced regularly (at 22 to 24 hours after the initiation of procedure), and will be continuously performed until 168 hours from the enrollment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator Free Days (VFD, Days alive and ventilator-free) | VFD is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFD) within 28 days. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | Fatalities, mortality all-causes | Up to Day 28, 60 and 90 | 
| Mortality in ICU | All-cause mortality for patients who died in Intensive Care Units. | Up to Day 28 | 
| Mortality in Hospital | The number of patients who died in hospital | Up to Day 28 | 
| Changes in PaO2/ FiO2 ratio |  | Up to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Diffuse Alveolar Damage, DAD, Acute Respiratory Distress Syndrome, ARDS, NOA-001, Hemoperfusion