Treatment of ARDS With Instilled T3 (ARDS+T3)

PHASE II RANDOMIZED, INTERVENTION VERSUS NON- INTERVENTION, MULTI- CENTER STUDY OF THE EFFECTS OF THYROID HORMONE (T3) ON SAFETY/TOLERABILITY AND OXYGENATION IN SUBJECTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid; Pulmonary Edema; ARDS, Human; Lung Inflammation; Lung, Wet
• Intervention / Treatment: Drug: Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.; Other: Non-intervention

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • M Health Fairview Southdale Hospital
    • Minneapolis, Minnesota, United States, 55455
      • East Bank Hospital - M Health Fairview University of Minnesota Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control arm; Standard of Care	Other: Non-intervention; Standard of Care (SOC)
Experimental: Treatment Arm; Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.	Drug: Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.; Study Drug Administration: Dose/Volume- Liothyronine Sodium 50 mcg / 10 mL; Frequency/Duration: Twice daily over 5 days (10 total doses), or until extubation, whichever comes first.; Method: Instilled via a catheter through the ETT directly into the airway.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	baseline
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	6 hours post-dose
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	12 hours post-dose
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	24 hours post-dose
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	48 hours post-dose
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	72 hours post-dose
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	96 hours post-dose
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	To assess the efficacy of airway instilled T3 improving oxygenation by reducing OI and OSI in ARDS patients. OI will be measured by mechanical ventilator (FIO2 and Mean Airway Pressure, MAP), and ABG (PaO2). OSI will be measured by mechanical ventilator (FIO2, SpO2 and MAP): OI = (FIO2 x MAP / PaO2). OSI = (FIO2 x MAP / SpO2).	120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary events	Progressive hemoptysis: bright, red blood in streaks, mixed or clots within sputum on suctioning of greater than 30 mL accumulation anytime following the initial and subsequent intratracheal dosing administrations.	baseline and 120 hours post-dose
Cardiovascular event 1	New sustained ventricular arrhythmia (>30 secs)	baseline to 120hours post-dose
Cardiovascular event 2	New sustained accelerated junctional arrhythmia (rate >80 bpm) with worsened hypotension (decrease in mean arterial pressure to less than 65mmHg).	baseline to 120hours post-dose
Cardiovascular event 3	New sustained atrial fibrillation with rapid ventricular response (ventricular rate >160 bpm) with worsened hypotension (decrease in mean arterial pressure to less than 65mmHg).	baseline to 120hours post-dose
Cardiovascular event 4	Cardiac arrest (pulseless electrical activity, or asystole).	baseline to 120hours post-dose
Cardiovascular event 5	Hypertensive crisis (systolic pressure of 180 mmHg (or higher), or diastolic pressure of 120 mmHg (or higher) or change in MAP > 20 mmHg with three consecutive measurements over 30 minutes).	baseline to 120hours post-dose
SOC pulmonary vasodilator	yes or no	baseline and 5 days
SOC pressor(s) dose(s)		baseline and 5 days
SOC diurectic(s) dose(s)		baseline and 5 days
Ventilator Free Days		baseline and 5 days
ICU Free Days		baseline and 5 days
Oxygen Free Days		baseline and 5 days
All-Cause Mortality		baseline and 5 days
Tracheostomy placement requirement		baseline and 5 days
Supplemental oxygen on discharge	yes or no	baseline and 5 days
Discharge disposition	home, inpatient rehabilitation, long-term acute care hospital (LTACH)	baseline and 5 days
TSH, Total T3, Free T3, Free T4		baseline and 156-hrs post-dose
Free T3, Free T4		baseline and 5 days

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Study Chair: David H Ingbar, MD, University of Minnesota; Study Director: Timothy P Rich, MD, University of Minnesota; Principal Investigator: Ronald A Reikoff, MD, University of Minnesota

Publications and helpful links

General Publications

• Flory CM, Norris BJ, Larson NA, Coicou LG, Koniar BL, Mysz MA, Rich TP, Ingbar DH, Schumacher RJ. A Preclinical Safety Study of Thyroid Hormone Instilled into the Lungs of Healthy Rats-an Investigational Therapy for ARDS. J Pharmacol Exp Ther. 2021 Jan;376(1):74-83. doi: 10.1124/jpet.120.000060. Epub 2020 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2020
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Thyroid Diseases; Respiratory Distress Syndrome; Pulmonary Edema; Pneumonia; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Aromatic; Amino Acids, Cyclic; Thyroid Hormones; Thyronines; Thyroxine; Triiodothyronine
• Other Study ID Numbers: PACS-2020-23242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No