Treatment of ARDS With Instilled T3

Phase 2

Recruiting

• Conditions: ARDS, Human; Lung, Wet; Thyroid; Pulmonary Edema; Lung Inflammation
• Interventions: Drug: Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.; Other: Non-intervention

• Registration Number: NCT04115514
• Lead Sponsor: University of Minnesota

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).

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-10-02
• Study First Posted: 2019-10-04
• Study Start: 2019-10-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26
• Primary Completion: 2025-10-31
• Study Completion: 2025-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 68

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.	Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.
Control arm	Non-intervention	Standard of Care

Primary Outcome Measures

Name	Time	Method
Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).	120 hours post-dose	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).

Secondary Outcome Measures

Name	Time	Method
Cardiovascular event 4	baseline to 120hours post-dose	Cardiac arrest (pulseless electrical activity, or asystole).
Cardiovascular event 5	baseline to 120hours post-dose	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).
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	baseline and 5 days	yes or no
Discharge disposition	baseline and 5 days	home, inpatient rehabilitation, long-term acute care hospital (LTACH)
Pulmonary events	baseline and 120 hours post-dose	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.
Cardiovascular event 1	baseline to 120hours post-dose	New sustained ventricular arrhythmia (\>30 secs)
Cardiovascular event 2	baseline to 120hours post-dose	New sustained accelerated junctional arrhythmia (rate \>80 bpm) with worsened hypotension (decrease in mean arterial pressure to less than 65mmHg).
Cardiovascular event 3	baseline to 120hours post-dose	New sustained atrial fibrillation with rapid ventricular response (ventricular rate \>160 bpm) with worsened hypotension (decrease in mean arterial pressure to less than 65mmHg).
SOC pressor(s) dose(s)	baseline and 5 days
SOC pulmonary vasodilator	baseline and 5 days	yes or no
TSH, Total T3, Free T3, Free T4	baseline and 156-hrs post-dose
Free T3, Free T4	baseline and 5 days

Trial Locations

Locations (2)

M Health Fairview Southdale Hospital; 🇺🇸 Edina, Minnesota, United States

East Bank Hospital - M Health Fairview University of Minnesota Medical Center; 🇺🇸 Minneapolis, Minnesota, United States