ARDS+T3: Treatment of ARDS With Instilled T3
Study Details
Study Description
Brief Summary
It is hypothesized that instillation of (T3) into the airspace will increase alveolar fluid clearance in patients with ARDS, resulting in reduced extravascular lung water (EVLW).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Randomized, unblinded, intervention versus non-intervention trial
Purpose: To determine the safety and tolerability of T3 delivery into the lungs of ARDS patients, and to measure the effect of T3 on EVLW index in ARDS patients.
Liothyronine Sodium (T3), 5-10-25-50µg will be instilled via catheter through ETT into the airways in a total volume of 10 ml (T3+0.9% sodium chloride) over 4 days (96 hours) with progressive dosing.
68 participants [50 treatment + 18 controls] will be investigated over 18 months or until target enrollment is achieved. No research intervention will occur with control subjects. Control subjects will receive standard of care.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active treatment Liothyronine Sodium (T3), 5-10-25-50µg instilled directly into the airways in a total volume of 10 ml (T3+0.9% sodium chloride). Progressive dosing every 24 hours for total 96 hours. |
Drug: Liothyronine Sodium (T3) (modified formulation)
Liothyronine Sodium (T3), 5-10-25-50µg instilled directly into the airways in a total volume of 10 ml (T3+0.9% sodium chloride). Progressive dosing every 24 hours for total 96 hours.
|
| No Intervention: Control arm Standard of Care |
Outcome Measures
Primary Outcome Measures
- Change in Extravascular Lung Water Index (EVLWI) [baseline, 1 hour post T3 installation]
EVLWI is calculated as ml of extravascular lung water fluid reported by VolumeView system (Edwards Lifesciences) divided by patient's body weight in kg. EVLWI will be measured at baseline and 1 hour post T3 installation to calculate change in EVLWI. Lower EVLWI values indicate greater treatment efficacy.
- Change in Extravascular Lung Water Index (EVLWI) [baseline, 12 hours post T3 installation]
EVLWI is calculated as ml of extravascular lung water fluid reported by VolumeView system (Edwards Lifesciences) divided by patient's body weight in kg. EVLWI will be measured at baseline and 12 hours post T3 installation to calculate change in EVLWI. Lower EVLWI values indicate greater treatment efficacy.
- Change in Extravascular Lung Water Index (EVLWI) [baseline, 24 hours post T3 installation]
EVLWI is calculated as ml of extravascular lung water fluid reported by VolumeView system (Edwards Lifesciences) divided by patient's body weight in kg. EVLWI will be measured at baseline and 24 hours post T3 installation to calculate change in EVLWI. Lower EVLWI values indicate greater treatment efficacy.
Secondary Outcome Measures
- Change in Arterial Oxygenation [On clinically indicated ABGs (about 1 hour after admission), then 24 hours post T3 installation]
Arterial partial pressure of oxygen will be sampled by arterial catheter (reported as mmHg) upon admission and then 24 hours after the first dose of T3 to calculate change in arterial partial pressure of oxygen. Increased arterial partial pressure of oxygen indicates greater treatment efficacy.
Eligibility Criteria
Criteria
Inclusion Criteria:
Clinical diagnosis of ARDS:
-
Chest x-ray: bilateral pulmonary infiltrates
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Hypoxemia: PaO2:FIO2 ratio <200
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Volume status: wedge and CVP<18
Main inclusion criteria:
-
Adults (≥18 years of age), non-pregnant
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On mechanical ventilatory support
Exclusion Criteria:
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Inadequate medical history for determining inclusion/exclusion criteria, as determined by the Principal Investigator and/or Sub-Investigators.
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Unlikely to complete the protocol with clinic follow-up after discharge, as determined by the Principal Investigator and/or Sub-Investigators or hospice status.
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Active drug/alcohol use with positive drug screen or alcohol level on admission.
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Prior history of thyroid cancer or hyperthyroidism, per thorough patient/family interviews, review of past medical history, medication list, laboratory test.
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Prior history of cardiovascular disease including:
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Hypertensive crisis in the past 3 months (systolic >200, or diastolic >120 mmHg),
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Sustained ventricular arrhythmia in the past 3 months (duration > 30 seconds)
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Coronary artery disease (documented >50% occlusion in any coronary vessel)
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Cardiac-related angina pectoris (> 2 episodes in the past 3 months)
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Myocardial infarction with ischemia on ECG (i.e., new ST-elevation/depression of
1mm in contiguous leads), or positive cardiac enzymes (Ratio of CK-MB: Total CK 3.5).
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Peripheral vascular disease (documented >50% occlusion in any peripheral vessel).
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Moderate or severe ischemic/non-ischemic cardiomyopathy (documented ejection fraction < 40%).
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Decompensated or symptomatic heart failure (i.e., hospitalized for CHF exacerbation, or a change in CHF medications within two weeks prior)
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Currently pregnant or breastfeeding.
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Currently taking tricyclic antidepressants, glycosides, ketamine, or vasopressors with ongoing evidence of myocardial ischemia.
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Known allergy to study drug.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Essentia Health - St. Mary's Medical Center | Duluth | Minnesota | United States | 55805 |
| 2 | M Health Fairview Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 3 | East Bank Hospital - M Health Fairview University of Minnesota Medical Center | Minneapolis | Minnesota | United States | 55455 |
| 4 | M Health Fairview St. Joseph's Hospital | Saint Paul | Minnesota | United States | 55102 |
| 5 | M Health Fairview Bethesda Hospital | Saint Paul | Minnesota | United States | 55103 |
Sponsors and Collaborators
- University of Minnesota
Investigators
- Principal Investigator: Timothy P Rich, MD, University of Minnesota
- Study Chair: David H Ingbar, MD, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 036127