Treatment of ARDS With Instilled T3

NCT04115514 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PACS-2020-23242
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

ARDS, Human; Lung, Wet; Thyroid; Pulmonary Edema; Lung Inflammation

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (18)

• Pulmonary events

  baseline and 120 hours post-dose

• Cardiovascular event 1

  baseline to 120hours post-dose

• Cardiovascular event 2

  baseline to 120hours post-dose

• Cardiovascular event 3

  baseline to 120hours post-dose

• Cardiovascular event 4

  baseline to 120hours post-dose

Study Arms (2)

Treatment Arm

EXPERIMENTAL

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.

Control arm

OTHER

Standard of Care

Other: Non-intervention

Interventions

Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation. DRUG

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.

Treatment Arm

Non-intervention OTHER

Standard of Care (SOC)

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Onset: \<= 7 days.
• Chest x-ray: Bilateral Patchy Opacities, Infiltrates.
• Mechanical Vent Support: PEEP or CPAP Support \>= 5 cm H2O.
• Pulmonary Edema: Not fully explained by cardiogenic etiology.
• 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.

You may not qualify if:

• Patients with any of the following conditions will be excluded from this trial:
• 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:
• Hypertensive crisis in the past 3 months (systolic \>200, or diastolic \>120 mmHg),
• Sustained ventricular arrhythmia in the past 3 months (duration \>30 seconds)
• Coronary artery disease (documented \>=70% occlusion untreated in any coronary vessel), as per the 2021 ACC/AHA/SCAI Guidelines for Coronary Artery Revascularization.
• Cardiac-related angina pectoris (\>=2 episodes in the past 3 months)
• Myocardial infarction with ischemia on ECG (i.e.,new ST- elevation/depression of \>1mm in contiguous leads).
• 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.
• 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.

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (2)

M Health Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

RECRUITING

East Bank Hospital - M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 33127750 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Pulmonary Edema; Thyroid Diseases; Pneumonia

Interventions

Triiodothyronine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Endocrine System Diseases; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Timothy P Rich, MD

  University of Minnesota

  STUDY DIRECTOR

• David H Ingbar, MD

  University of Minnesota

  STUDY CHAIR

• Ronald A Reikoff, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Rhodes

CONTACT

frak0001@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: None applicable
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, unblinded, intervention versus non-intervention trial. 68 \[50 treatment + 18 controls\]

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: October 4, 2019
• Study Start: March 30, 2020
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)