It is hypothesized that instillation of Liothyronine Sodium (T3) into the airspace will be safe, well tolerated, and will increase alveolar fluid clearance and decrease inflammation in patients with ARDS, reflected in improved oxygenation index (OI) and oxygenation saturation index (OSI).

T3 Therapy in ARDS- Phase 2 Randomized, Unblinded, Intervention versus Non- Intervention Trial. Enrollment 68 participants (50 treatment + 18 control). Purpose- To determine the safety and tolerability of T3 delivery into the lungs of ARDS patients, and to measure the effect of T3 on Oxygenation in ARDS patients. Study Drug- Liothyronine Sodium (T3), 50 mcg will be instilled twice daily via a catheter through the ETT into the airway in a total volume of 10 mL (T3+0.9% sodium chloride), over 5 days (10 total doses), or until extubation, whichever comes first.

Inclusion Criteria:

Study population is critically ill patients requiring mechanical ventilatory support for ARDS in an intensive care unit.

• Adults (≥18 years of age).

• Male or female (non-pregnant).

• Clinical diagnosis of ARDS (all are required):

  1. Onset: <= 7 days.
  2. Chest x-ray: Bilateral Patchy Opacities, Infiltrates.
  3. Mechanical Vent Support: PEEP or CPAP Support >= 5 cm H2O.
  4. Pulmonary Edema: Not fully explained by cardiogenic etiology.
  5. Hypoxia: PaO2/FIO2 Ratio <300, or O2Sat/FIO2 Ratio <315.

• On mechanical ventilatory support.

• Capable of giving informed consent directly or from the subject's legally authorized representative (LAR) as determined by the site Principal Investigator and/or Sub- Investigators.

Exclusion Criteria:

Patients with any of the following conditions will be excluded from this trial:

• Inadequate medical history for determining inclusion/exclusion criteria, as determined by the Principal Investigator and/or Sub- Investigators.

• Unlikely to complete the protocol with clinic follow-up after discharge, as determined by the Principal Investigator and/or Sub- Investigators or hospice status.

• Prior history of thyroid cancer or hyperthyroidism, per thorough patient/family interviews, review of past medical history, medication list, laboratory test.

• Prior history of cardiovascular disease defined as:

  1. Hypertensive crisis in the past 3 months (systolic >200, or diastolic >120 mmHg),
  2. Sustained ventricular arrhythmia in the past 3 months (duration >30 seconds)
  3. Coronary artery disease (documented >=70% occlusion untreated in any coronary vessel), as per the 2021 ACC/AHA/SCAI Guidelines for Coronary Artery Revascularization.
  4. Cardiac-related angina pectoris (>=2 episodes in the past 3 months)
  5. Myocardial infarction with ischemia on ECG (i.e.,new ST- elevation/depression of >1mm in contiguous leads).
  6. Peripheral vascular disease (documented >=70% occlusion untreated in any peripheral vessel), as per the 2018 ACC/AHA/SCAI/SIR/SVM Guidelines for Appropriate Use Criteria for Peripheral Artery Intervention.
  7. Decompensated or symptomatic heart failure (i.e., hospitalized for CHF exacerbation, or a change in CHF medications within two weeks prior)

• Currently pregnant or breastfeeding.

• Known allergy to study drug.

None applicable