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Treatment of ARDS With Instilled T3 (ARDS+T3)

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ClinicalTrials.gov Identifier: NCT04115514
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : October 3, 2022
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

Tracking Information
First Submitted Date  ICMJE March 12, 2019
First Posted Date  ICMJE October 4, 2019
Last Update Posted Date October 3, 2022
Actual Study Start Date  ICMJE October 21, 2019
Estimated Primary Completion Date October 10, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2019)
  • Change in Extravascular Lung Water Index (EVLWI) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2019)		 Change in Arterial Oxygenation [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of ARDS With Instilled T3
Official Title  ICMJE Phase II Randomized, Intervention Versus Non-Intervention, Multi-center Study of the Effects of Thyroid Hormone (T3) on Extravascular Lung Water (EVLW) in Subjects With Acute Respiratory Distress Syndrome (ARDS)
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, unblinded, intervention versus non-intervention trial. 68 [50 treatment + 18 controls]
Masking: None (Open Label)
Masking Description:
None applicable
Primary Purpose: Treatment
Condition  ICMJE
  • ARDS, Human
  • Lung, Wet
  • Thyroid
  • Pulmonary Edema
  • Lung Inflammation
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Liothyronine Sodium (T3) (modified formulation)
  • No Intervention: Control arm
    Standard of Care
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 2, 2019)		 68
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 10, 2023
Estimated Primary Completion Date October 10, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Clinical diagnosis of ARDS:

  • Chest x-ray: bilateral pulmonary infiltrates
  • Hypoxemia: PaO2:FIO2 ratio <200
  • Volume status: wedge and CVP<18

Main inclusion criteria:

  • Adults (≥18 years of age), non-pregnant
  • On mechanical ventilatory support

Exclusion Criteria:

  1. Inadequate medical history for determining inclusion/exclusion criteria, as determined by the Principal Investigator and/or Sub-Investigators.
  2. Unlikely to complete the protocol with clinic follow-up after discharge, as determined by the Principal Investigator and/or Sub-Investigators or hospice status.
  3. Active drug/alcohol use with positive drug screen or alcohol level on admission.
  4. Prior history of thyroid cancer or hyperthyroidism, per thorough patient/family interviews, review of past medical history, medication list, laboratory test.

  5. Prior history of cardiovascular disease including:

    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 >50% occlusion in any coronary vessel)
    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), or positive cardiac enzymes (Ratio of CK-MB: Total CK > 3.5).
    6. Peripheral vascular disease (documented >50% occlusion in any peripheral vessel).
    7. Moderate or severe ischemic/non-ischemic cardiomyopathy (documented ejection fraction < 40%).
    8. Decompensated or symptomatic heart failure (i.e., hospitalized for CHF exacerbation, or a change in CHF medications within two weeks prior)
  6. Currently pregnant or breastfeeding.
  7. Currently taking tricyclic antidepressants, glycosides, ketamine, or vasopressors with ongoing evidence of myocardial ischemia.
  8. Known allergy to study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kelly M McCormick, MBA, MSL 6126243315 kmmccorm@umn.edu
Contact: Melisa A Bailey, MS 6126242627 baile807@umn.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04115514
Other Study ID Numbers  ICMJE 036127
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party University of Minnesota
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Minnesota
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Timothy P Rich, MD University of Minnesota
Study Chair: David H Ingbar, MD University of Minnesota
PRS Account University of Minnesota
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP