Effect of Inhaled Nitric Oxide Therapy in Adults With Moderate-to-Severe Acute Respiratory Distress Syndrome

Evaluation of the Efficacy of Inhaled Nitric Oxide Therapy in Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Multicenter, Prospective, Randomized Controlled Clinical Trial (ENARCT-ARDS)

The goal of this clinical trial is to evaluate whether inhaled nitric oxide (iNO), added to standard care, can reduce mortality in adults with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS). The main questions it aims to answer are:

Does iNO therapy reduce 28-day all-cause mortality compared to standard care alone? Does iNO therapy increase the number of ventilator-free days through day 28? If there is a comparison group: Researchers will compare the group receiving iNO plus standard care with the group receiving placebo plus standard care to see if iNO improves survival and other clinical outcomes.

Participants will:

Be randomly assigned to receive either iNO or a placebo through the ventilator.

Receive all other standard treatments for ARDS as per current guidelines. Be closely monitored for 28 days to track survival, time on the ventilator, and safety.

Inclusion Criteria:

• Age ≥ 18 years.
• Patients diagnosed with moderate-to-severe ARDS according to the 2023 Global (or international) criteria.

Exclusion Criteria:

• Known allergy to iNO.
• Congenital methemoglobinemia.
• End-stage chronic lung disease (e.g., lung cancer, prior pneumonectomy/lung transplant).
• Shock (norepinephrine >0.5 μg/kg/min or equivalent for >6 hours) at treatment initiation.
• Pulmonary hypertension (PASP >45 mmHg by echo or mPAP ≥25 mmHg by catheterization).
• Serum creatinine >2.5 mg/dL (221 μmol/L).
• Major bleeding (e.g., intracranial, pulmonary) or platelet count <20×10⁹/L.
• Expected ICU/mechanical ventilation <24 hours.
• Pre-enrollment ECMO therapy.
• Any investigator-assessed unsuitability for the study.