Clinical trial NCT04115514: Treatment of ARDS With Instilled 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: ARDS, Human
Lung, Wet
Thyroid
Pulmonary Edema
Lung Inflammation
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2019-10-04
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, unblinded, intervention versus non-intervention trial. 68 \[50 treatment + 18 controls\]
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: baseline
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 6 hours post-dose
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 12 hours post-dose
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 24 hours post-dose
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 48 hours post-dose
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 72 hours post-dose
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 96 hours post-dose
measure: Oxygenation: Oxygenation Index (OI), and/or Oxygenation Saturation Index (OSI).
timeFrame: 120 hours post-dose
Secondary outcomes:
measure: Pulmonary events
timeFrame: baseline and 120 hours post-dose
measure: Cardiovascular event 1
timeFrame: baseline to 120hours post-dose
measure: Cardiovascular event 2
timeFrame: baseline to 120hours post-dose
measure: Cardiovascular event 3
timeFrame: baseline to 120hours post-dose
measure: Cardiovascular event 4
timeFrame: baseline to 120hours post-dose
measure: Cardiovascular event 5
timeFrame: baseline to 120hours post-dose
measure: SOC pulmonary vasodilator
timeFrame: baseline and 5 days
measure: SOC pressor(s) dose(s)
timeFrame: baseline and 5 days
measure: SOC diurectic(s) dose(s)
timeFrame: baseline and 5 days
measure: Ventilator Free Days
timeFrame: baseline and 5 days
measure: ICU Free Days
timeFrame: baseline and 5 days
measure: Oxygen Free Days
timeFrame: baseline and 5 days
measure: All-Cause Mortality
timeFrame: baseline and 5 days
measure: Tracheostomy placement requirement
timeFrame: baseline and 5 days
measure: Supplemental oxygen on discharge
timeFrame: baseline and 5 days
measure: Discharge disposition
timeFrame: baseline and 5 days
measure: TSH, Total T3, Free T3, Free T4
timeFrame: baseline and 156-hrs post-dose
measure: Free T3, Free T4
timeFrame: baseline and 5 days
Other outcomes:
Locations:
city: Edina
country: United States
facility: M Health Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: East Bank Hospital - M Health Fairview University of Minnesota Medical Center
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Timothy P Rich, MD
role: STUDY_DIRECTOR
affiliation: University of Minnesota
name: David H Ingbar, MD
role: STUDY_CHAIR
affiliation: University of Minnesota
name: Ronald A Reikoff, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.