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

Phase 2
Terminated
Conditions
Pulmonary Infection
Covid-19
Interventions
Registration Number
NCT04348513
Lead Sponsor
Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
5
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
T3 solution for injectionT3 solution for injectionT3 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).
PlaceboPlaceboComposition identical apart from the active substance. Same dosage.
Primary Outcome Measures
NameTimeMethod
Assessment of weaning from cardiorespiratory support30 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
NameTimeMethod
Assessment of cardiac function30 days

Echocardiographic assessment of cardiac left ventricular ejection fraction (LVEF, %)

Assessment of cardiac injury30 days

Measurements of cardiac troponin I (in μg/L) will be used to assess myocardial injury

Assessment of hepatic function30 days

Hepatic function will be assessed by laboratory measurements in blood. Changes in d-dimers in ng/ml will be measured.

Assessment of pulmonary function30 days

Pulmonary function will be assessed by arterial measurement of lactate levels (in mmol/L)

Assessment of the course of COVID-19 infection30 days

COVID-19 infection will be assessed by time needed (in days) for the patient to become negative in COVID-19

Assessment of hemodynamic status30 days

Hemodynamic status will be assessed by the number of participants with use of inotropic and vasoactive drugs

Assessment of renal function30 days

Changes in creatinine (in mg/dL) will be recorded.

Assessment of clinical outcome and safety30 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

Trial Locations

Locations (1)

Attikon University General Hospital

🇬🇷

Haidari/Athens, Greece

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