ARDS, Human, Lung Inflammation, Lung, Wet, Pulmonary Edema, Thyroid
Conditions
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.
Interventions
DRUGLiothyronine 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.
OTHERNon-intervention
Standard of Care (SOC)
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None applicable
Intervention model description
Randomized, unblinded, intervention versus non-intervention trial. 68 \[50 treatment + 18 controls\]
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI). | baseline | 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 pulmonary vasodilator | baseline and 5 days | yes or no |
| 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 | baseline and 5 days | yes or no |
| Discharge disposition | baseline and 5 days | home, inpatient rehabilitation, long-term acute care hospital (LTACH) |
| TSH, Total T3, Free T3, Free T4 | baseline and 156-hrs post-dose | — |
| Free T3, Free T4 | baseline and 5 days | — |
Countries
United States
Contacts
STUDY_DIRECTORTimothy P Rich, MD
University of Minnesota
STUDY_CHAIRDavid H Ingbar, MD
University of Minnesota
PRINCIPAL_INVESTIGATORRonald A Reikoff, MD
University of Minnesota
Outcome results
None listed