Direct Topical Lung T3 Treatment to Improve Outcome & Sequelae of COVID-19 Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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Acute treatment of COVID-ARDS with direct topical lung instilled T3 therapy for patients on mechanical ventilation.

Detailed Description
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Post-hospitalization follow-up for 6 and 12-months of survival and end-organ dysfunction (lung, heart, kidney, neuropsychological), plus quality of life and return to work of those previously working

Official Title
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Phase II Trial of Direct Topical Lung T3 Treatment to Improve Outcome & Sequelae of COVID-19 ARDS - A Multi-Site, Randomized, Double-blinded, Placebo-Controlled Clinical Trial

Conditions
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Covid19, SARS-CoV Infection, ARDS, ARDS, Human

Intervention / Treatment
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* Drug: Instilled T3
* Other: Placebo Therapy


Participation Criteria
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Eligibility Criteria
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Exclusion Criteria: Pregnancy Inclusion Criteria: Diagnosis of SARS-CoV-2 with first positive test within 14 days, and, Diagnosis of ARDS by the Berlin Criteria (2012): Onset: < 7 days Chest x-ray: Bilateral Patchy Opacities, Infiltrates Mechanical Vent Support: PEEP or CPAP Support >= 5 cm H2O Pulmonary Edema: Not fully explained by cardiogenic etiology Hypoxia: PaO2/FIO2 Ratio < 300, or O2Sat/FIO2 Ratio < 315

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T3 Intervention<br>Participants in this arm will receive the experimental intervention. | Drug: Instilled T3<br>* The first dose of T3 (50 micrograms in 10 mls volume BID) will be instilled by an investigator or under their direct supervision within 48 hours of obtaining consent after verifying that the patient is not too unstable to treat at that time. T3 doses will be given in 50 mcg doses twice daily for 4 days.<br>|
| Placebo Comparator: Placebo Therapy<br>Participants in this arm will receive placebo therapy. | Other: Placebo Therapy<br>* A placebo therapy will be instilled into the lungs by the investigator or under their direct supervision within 48 hours of obtaining consent after verifying that the patient is not too unstable to treat at that time. Doses will be given twice daily for 4 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change Extravascular Lung Water Index | 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. | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of ICU Stay | Outcome is reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm. | Baseline to ICU discharge up to 30 days | 
| Number of Ventilator-Free Days | Outcome is reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission. | 30 days | 
| 30-day Survival | Outcome is reported as the number of participants in each arm who are alive 30-days post enrollment. | 30 days | 
| Creatinine Concentration | Outcome is reported as the number of participants in each arm with abnormally high plasma creatinine concentration (greater 1.21 milligrams per deciliter). | 4 days | 
| Glomerular Filtration Rate | Outcome is reported as the number of participants in each arm with impaired kidney function, defined as a glomerular filtration rate (GFR) less than 60 mL/min/1.73 m^2. | 4 days | 
| New York Heart Association (NYHA) Functional Classification | Outcome is reported as the number of participants in each arm who fall into each of 4 categories: 1 (no limitation in normal physical activity), 2 (mild symptoms only in normal activity), 3 (marked symptoms during daily activities, asymptomatic only at rest), and 4 (severe limitations, symptoms even at rest). | 30 days |