Treatment of ARDS With Instilled T3

ARDS, Human Clinical Trial

— ARDS+T3  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04115514
• Other study ID #: 036127
• Status: Recruiting
• Phase: Phase 2
• Start date: October 21, 2019
• Est. completion date: October 31, 2024

Study information

• Verified date: October 2023
• Source: University of Minnesota
• Contact: Melissa Rhodes
• Email: frak0001[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ARDS, Human
• Inflammation
• Lung Inflammation
• Lung, Wet
• Pneumonia
• Pulmonary Edema
• Respiratory Distress Syndrome
• Thyroid

Intervention

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.

Other:
• Non-intervention
Standard of Care (SOC)

Locations

Country	Name	City	State
United States	M Health Fairview Southdale Hospital	Edina	Minnesota
United States	East Bank Hospital - M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Cardiovascular event 1	New sustained ventricular arrhythmia (>30 secs)	baseline to 120hours post-dose
Secondary	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
Secondary	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
Secondary	Cardiovascular event 4	Cardiac arrest (pulseless electrical activity, or asystole).	baseline to 120hours post-dose
Secondary	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
Secondary	SOC pulmonary vasodilator	yes or no	baseline and 5 days
Secondary	SOC pressor(s) dose(s)		baseline and 5 days
Secondary	SOC diurectic(s) dose(s)		baseline and 5 days
Secondary	Ventilator Free Days		baseline and 5 days
Secondary	ICU Free Days		baseline and 5 days
Secondary	Oxygen Free Days		baseline and 5 days
Secondary	All-Cause Mortality		baseline and 5 days
Secondary	Tracheostomy placement requirement		baseline and 5 days
Secondary	Supplemental oxygen on discharge	yes or no	baseline and 5 days
Secondary	Discharge disposition	home, inpatient rehabilitation, long-term acute care hospital (LTACH)	baseline and 5 days
Secondary	TSH, Total T3, Free T3, Free T4		baseline and 156-hrs post-dose
Secondary	Free T3, Free T4		baseline and 5 days