Add-on Reparixin in Adult Patients With ARDS

Inclusion Criteria:

1. Signed Informed Consent, according to local guidelines and regulation.

2. Male and female adults (>18 years old).

3. Mechanically ventilated (invasive) patients with PaO2/FIO2 ratio ≤200 in thepresence of PEEP of ≥5 cmH20.

4. Respiratory failure not fully explained by cardiac failure or fluid overload (ifacute Congestive Heart Failure exacerbation is identified as part of the clinicalpicture this should be addressed effectively and as soon as possible before thepatient can be enrolled).

5. Bilateral radiologic opacities consistent with pulmonary edema on the frontal chestx-ray (CXR), or bilateral ground glass opacities on a chest computerized tomography (CT) scan.

6. ≤48 hours from fulfilling above ARDS criteria (if a patient is transferred from anon-participating hospital to a participating site a 12-hour period beyond the 48hours is allowed)

7. Females of child-bearing potential who are sexually active must be willing not toget pregnant within 30 days after the last Investigational Medicinal Product (IMP)dose and must agree to at least one of the following reliable methods ofcontraception:

8. Hormonal contraception, systemic, implantable, transdermal, or injectablecontraceptives from at least 2 months before the screening visit until 30 daysafter the last IMP dose;

9. A sterile sexual partner;

10. Abstinence. In patients non able to personally consent to above due tocomplications of acute illness and/or its treatment assurances for the abovemust be given by LR and reiterated by patient when/if she is able to do so.

Female participants of non-child-bearing potential or in post- menopausal status for at least 1 year will be admitted. For all female subjects with child-bearing potential, pregnancy test result must be negative before first drug intake.

Exclusion Criteria:

1. Moderate-Severe chronic hepatic disease (as verified by a previously knownChild-Pugh score ≥7). If baseline Child-Pugh score is not known it should not becalculated while the patient is acutely ill. In that case the patient is excluded onthe basis of: ALT/AST ≥ 3x ULN and total bilirubin > 2x ULN or ALT/AST ≥ 5x ULN

2. Severe chronic renal dysfunction: eGFR (2021 CKD-EPI) < 30 mL/min/1.73m2. Ifbaseline (chronic) renal function is not known the patient is only excluded if inneed of acute renal replacement therapy (currently on RRT or to be imminently placedon RRT)

3. Participation in another interventional clinical trial.

4. Patients that are clinically determined to have a high likelihood of death withinthe next 24 hours based on PI's estimation.

5. Currently receiving ECMO or high frequency oscillatory ventilation.

6. Anticipated extubation within 24 hours of screening. (In such cases re-screening isallowed if the patient is within the enrollment window).

7. Evidence of GI dysmotility as demonstrated by presence of all the following:persistent gastric distention and enteral feeding intolerability and persistentgastric residuals >500 ml).

8. Anticipated transfer to a hospital not participating in the trial within 72 hours ofscreening.

9. Decision to withhold or withdraw life-sustaining treatment (patients may still beeligible however if they are committed to full support except cardiopulmonaryresuscitation if cardiac arrest occurs).

10. History of:

11. Documented allergy/hypersensitivity to sulfonamides, ibuprofen and other COX-1and 2 inhibitors, and to the study product and/or its excipients.

12. Lactase deficiency, galactosemia or glucose-galactose malabsorption.

13. History of peptic ulcer, GI bleeding or perforation due to previous NSAIDtherapy.

14. Active bleeding (excluding menses) from uncontrolled site that cannot bedefinitively resolved prior to enrollment.

15. Pregnant or lactating women.

16. Women of childbearing potential and fertile men who do not agree to use at least oneprimary form of contraception during the study and up to 30 days after the last IMPdose. For patients non able to personally consent to above due to complications ofacute illness and/or its treatment assurances for the above must be given by LR andreiterated by patient when/if he/she is able to do so.