Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection (Thy-Support)

• ClinicalTrials.gov Identifier: NCT04348513
• Recruitment Status: Not yet recruiting
• First Posted: April 16, 2020
• Last Update Posted: April 16, 2020
• Sponsor: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
• Collaborator: ATTIKON University Hospital
• Information provided by (Responsible Party): Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

Study Description

Brief Summary:

This study is a phase II, parallel, prospective, randomized, double-blind, placebo controlled trial. The present study will aim to address the efficacy and safety of acute administration of triiodothyronine on ICU patients diagnosed with pulmonary infection due to COVID-19 and require mechanical respiratory support or ECMO.

Condition or disease	Intervention/treatment	Phase
Pulmonary Infection; Covid-19	Drug: T3 solution for injection; Drug: Placebo	Phase 2

Detailed Description:

It seems that thyroid hormone is critical in the response to body injury and is now considered as potential pharmaceutical intervention to limit acute tissue injury. TH (via its regulation of stress induced p38 MAPK activation) exerts antiapoptotic action and protects tissue from injury, with additional favorable effects on immune system and on viral load in infected tissue. This may be a novel and more effective treatment for critically ill viral infected patients.

ThyRepair is the first study which is underway and investigates the safety and efficacy of high dose T3 treatment in patients with acute myocardial infarction undergoing primary angioplasty. The preliminary reports show that this treatment is safe and the efficacy on tissue repair is promising. This therapeutic modality could also be tested in the acute setting of sepsis in which thyroid hormone is involved in the pathophysiology of multi-organ dysfunction. The safety and efficacy of T3 on heamodynamics in sepsis has been previously demonstrated in a small trial.

The present study is phase II, parallel, prospective, randomized, double-blind, placebo controlled trial which aims to investigate the potential effect of T3 intravenous use in the recovery of critically ill patients admitted in ICU due to COVID19 infection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Phase II, parallel, prospective, randomized, double-blind, placebo controlled trial
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection (Thy-Support)
• Estimated Study Start Date: May 2, 2020
• Estimated Primary Completion Date: May 2, 2021
• Estimated Study Completion Date: May 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: T3 solution for injection; T3 Solution for injection 10 μg/ml, each vial contains 150μg of liothyronine in a total volume of 15ml. The dose administered will be 0.8g/kg i.v. bolus starting within 60min after respiratory support and will be followed by an infusion of 0.113g. kg-1.h-1 i.v. for 48 hours (therapeutic dose). After the first 48h, a maintenance dose will be administered corresponding to 50% of the therapeutic dose (0.057g. kg-1.h-1 i.v.). Drug administration will stop after successful weaning or end of followup (maximum 30 days).	Drug: T3 solution for injection; For example, for a patient of 77Kg of weight, a dose of 6ml (60 μg) will be administered as a bolus intravenously over 2-3 min within 60 min of respiratory support initiation. Then, the patient for the next 24 hours will receive 21ml of the product (total of 210 μg of T3) that will be diluted in NaCl 0.9% and administered with a pump at a steady flow rate of 10.4 ml/h for a total duration of 48 hours. From day 3 till successful weaning or end of follow-up, the patient will receive 50% of this dose, 10.5 ml of the product (total of 105 μg of T3) that will be diluted in NaCl 0.9% and administered with a pump at a steady flow rate of 5.2 ml/h.
Placebo Comparator: Placebo; Composition identical apart from the active substance. Same dosage.	Drug: Placebo; Same as with T3 solution for injection.

Outcome Measures

Primary Outcome Measures :

1. Assessment of weaning from cardiorespiratory support [ Time Frame: 30 days ]
   The primary objective of the study is to determine whether the administration of intravenous triiodothyronine in ICU patients diagnosed with pulmonary infection due to COVID-19 facilitates weaning from cardiorespiratory support compared to placebo. Successful weaning is defined as no requirement for ventilatory support after extubation (mechanical support) or support from ECMO for 48 hours. The primary objective will be measured as percentage of patients successfully weaned after 30 days of follow-up.

Secondary Outcome Measures :

1. Assessment of hemodynamic status [ Time Frame: 30 days ]
   Hemodynamic status will be assessed by continuous blood pressure measurements (systolic BP in mmHg)
2. Assessment of hemodynamic status [ Time Frame: 30 days ]
   Hemodynamic status will be assessed by continuous blood pressure measurements (diastolic BP in mmHg)
3. Assessment of hemodynamic status [ Time Frame: 30 days ]
   Hemodynamic status will be assessed by continuous blood pressure measurements (mean BP in mmHg)
4. Assessment of hemodynamic status [ Time Frame: 30 days ]
   Hemodynamic status will be assessed by the number of participants with use of inotropic and vasoactive drugs
5. Assessment of pulmonary function [ Time Frame: 30 days ]
   Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of oxygen in mmHg)
6. Assessment of pulmonary function [ Time Frame: 30 days ]
   Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of carbon dioxide in mmHg)
7. Assessment of pulmonary function [ Time Frame: 30 days ]
   Pulmonary function will be assessed by arterial measurement of lactate levels (in mmol/L)
8. Assessment of hepatic function [ Time Frame: 30 days ]
   Hepatic function will be assessed by laboratory measurements in blood. Changes in aspartate aminotransferase (AST in IU/L) will be measured.
9. Assessment of hepatic function [ Time Frame: 30 days ]
   Hepatic function will be assessed by laboratory measurements in blood. Changes in alanine aminotransferase (ALT in IU/L) will be measured.
10. Assessment of hepatic function [ Time Frame: 30 days ]
    Hepatic function will be assessed by laboratory measurements in blood. Changes in gamma-glutamyl transpeptidase (γ-GT in IU/L) will be measured.
11. Assessment of hepatic function [ Time Frame: 30 days ]
    Hepatic function will be assessed by laboratory measurements in blood. Changes in bilirubin in mg/dL will be measured.
12. Assessment of hepatic function [ Time Frame: 30 days ]
    Hepatic function will be assessed by laboratory measurements in blood. Changes in fibrinogen in mg/dL will be measured.
13. Assessment of hepatic function [ Time Frame: 30 days ]
    Hepatic function will be assessed by laboratory measurements in blood. Changes in d-dimers in ng/ml will be measured.
14. Assessment of renal function [ Time Frame: 30 days ]
    Urine volume during 24 hours (in ml) will be recorded.
15. Assessment of renal function [ Time Frame: 30 days ]
    Changes in urea (in mg/dL) will be recorded.
16. Assessment of renal function [ Time Frame: 30 days ]
    Changes in uric acid (in mg/dL) will be recorded.
17. Assessment of renal function [ Time Frame: 30 days ]
    Changes in creatinine (in mg/dL) will be recorded.
18. Assessment of cardiac function [ Time Frame: 30 days ]
    Echocardiographic assessment of cardiac left ventricular ejection fraction (LVEF, %)
19. Assessment of cardiac injury [ Time Frame: 30 days ]
    Measurements of cardiac troponin I (in μg/L) will be used to assess myocardial injury
20. Assessment of the course of COVID-19 infection [ Time Frame: 30 days ]
    COVID-19 infection will be assessed by inflammatory indices in blood (white blood cells in number per μL)
21. Assessment of the course of COVID-19 infection [ Time Frame: 30 days ]
    COVID-19 infection will be assessed by inflammatory indices in blood (CRP in mg/L)
22. Assessment of the course of COVID-19 infection [ Time Frame: 30 days ]
    COVID-19 infection will be assessed by inflammatory indices in blood (erythrocyte sedimentation rate in mm/hr)
23. Assessment of the course of COVID-19 infection [ Time Frame: 30 days ]
    COVID-19 infection will be assessed by temperature monitoring (in degrees Celsius)
24. Assessment of the course of COVID-19 infection [ Time Frame: 30 days ]
    COVID-19 infection will be assessed by time needed (in days) for the patient to become negative in COVID-19
25. Assessment of clinical outcome and safety [ Time Frame: 30 days ]
    Number of participants with major (death, cardiac Arrest, electromechanical dissociation, pulmonary embolism, new myocardial infarction, stroke, pulmonary edema, cardiogenic shock and hypotension, septic shock, pulmonary embolism, serious bleeding) events be recorded during the follow up period
26. Assessment of clinical outcome and safety [ Time Frame: 30 days ]
    Number of participants with minor (myocarditis, Venous Thromboembolism, left Ventricular mural thrombus, renal failure, hepatic failure, stress ulcers, minor bleeding, paroxysmal supraventricular tachycardia and atrial fibrillation, rhythm disturbances) events will be recorded during the follow up period

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients diagnosed with pulmonary infection due to COVID-19, admitted in ICU and require mechanical ventilation or ECMO
• Male and female with Age>18 years old
• Signed informed consent from patient or relatives

Exclusion Criteria:

• Pregnant or breast-feeding women
• Severe systemic disease (cancer, auto-immune etc) before infection accompanied by reduced life expectancy <6 months
• Participation in another trial of an investigational drug or device
• Corticosteroid Use before initiation of treatment
• Sympathomimetic Use before initiation of treatment (epinephrine, norepinephrine, dobutamine, dopamine, phenylephrine)

Contacts and Locations

Locations

Greece

Attikon University General Hospital

Haidari/Athens, Greece, 12462

Contact: Georgia Kostopanagiotou, MD +30 210 5831000 gkostopan@med.uoa.gr

Principal Investigator: Georgia Kostopanagiotou, MD

Principal Investigator: Apostolos Armaganidis, MD

Sponsors and Collaborators

Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

ATTIKON University Hospital

Investigators

• Principal Investigator: Georgia Kostopanagiotou, MD; ATTIKON University General Hospital

More Information

• Responsible Party: Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
• ClinicalTrials.gov Identifier: NCT04348513
• Other Study ID Numbers: T3inj-02/ThySupport
• First Posted: April 16, 2020
• Last Update Posted: April 16, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.:

Covid-19; Pulmonary Infection; T3; Triiodothyronine; SARS-CoV-2

Additional relevant MeSH terms:

Infection; Communicable Diseases