Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection

NCT ID: NCT04348513

Last Updated: 2021-09-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-29
• Study Completion Date: 2021-04-19

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.

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.

Conditions

Pulmonary Infection; Covid-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

T3 solution for injection

Intervention Type: DRUG

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

Composition identical apart from the active substance. Same dosage.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Same as with T3 solution for injection.

Interventions

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.

Intervention Type: DRUG

Placebo

Same as with T3 solution for injection.

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Attikon Hospital

OTHER

Sponsor Role: collaborator

Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Georgia Kostopanagiotou, MD

Role: PRINCIPAL_INVESTIGATOR

ATTIKON University General Hospital

Locations

Attikon University General Hospital

Haidari/Athens, , Greece

Countries

Greece

References

Pantos C, Apostolaki V, Kokkinos L, Trikas A, Mourouzis I. Acute triiodothyronine treatment and red blood cell sedimentation rate (ESR) in critically ill COVID-19 patients: A novel association? Clin Hemorheol Microcirc. 2021;79(3):485-488. doi: 10.3233/CH-211215.

Reference Type: DERIVED

PMID: 34151781 (View on PubMed)

Pantos C, Kostopanagiotou G, Armaganidis A, Trikas A, Tseti I, Mourouzis I. Triiodothyronine for the treatment of critically ill patients with COVID-19 infection: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 26;21(1):573. doi: 10.1186/s13063-020-04474-0.

Reference Type: DERIVED

PMID: 32586399 (View on PubMed)

Other Identifiers

T3inj-02/ThySupport

Identifier Type: -

Identifier Source: org_study_id