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

• ClinicalTrials.gov Identifier: NCT04725110
• Recruitment Status: Recruiting
• First Posted: January 26, 2021
• Last Update Posted: September 6, 2022
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Covid19; SARS-CoV Infection; ARDS; ARDS, Human	Drug: Instilled T3; Other: Placebo Therapy	Phase 2

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 29, 2019
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: March 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: T3 Intervention; Participants in this arm will receive the experimental intervention.	Drug: Instilled T3; 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.
Placebo Comparator: Placebo Therapy; Participants in this arm will receive placebo therapy.	Other: Placebo Therapy; 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.

Outcome Measures

Primary Outcome Measures :

1. Change Extravascular Lung Water Index [ Time Frame: 1 hour ]
   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.

Secondary Outcome Measures :

1. Length of ICU Stay [ Time Frame: Baseline to ICU discharge up to 30 days ]
   Outcome is reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
2. Number of Ventilator-Free Days [ Time Frame: 30 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.
3. 30-day Survival [ Time Frame: 30 days ]
   Outcome is reported as the number of participants in each arm who are alive 30-days post enrollment.
4. Creatinine Concentration [ Time Frame: 4 days ]
   Outcome is reported as the number of participants in each arm with abnormally high plasma creatinine concentration (greater 1.21 milligrams per deciliter).
5. Glomerular Filtration Rate [ Time Frame: 4 days ]
   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.
6. New York Heart Association (NYHA) Functional Classification [ Time Frame: 30 days ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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):

  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

Contacts and Locations

Contacts

Contact: Kelly McCormick, MBA, MSL; 6126243315; kmmccorm@umn.edu

Contact: Melisa Bailey; 6126242627; baile807@umn.edu

Locations

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55117

Contact: Kelly M McCormick kmmccorm@umn.ediu

Principal Investigator: David Ingbar, MD

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Timothy P Rich, MD; University of Minnesota
• Study Chair: David Ingbar, MD; University of Minnesota

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04725110
• Other Study ID Numbers: ARDS NIH Grant
• First Posted: January 26, 2021
• Last Update Posted: September 6, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders