Improvement of severe respiratory failure in Covid-19 patients

INTERVENTION: Trade Name: NATRIUM THIOSULFAT 25% Product Name: NATRIUMTHIOSULFAT 25% Pharmaceutical Form: Solution for infusion INN or Proposed INN: SODIUM THIOSULFATE CAS Number: 7772‐98‐7 Other descriptive name: SODIUM THIOSULFATE Concentration unit: g/ml gram(s)/millilitre Concentration type: equal Concentration number: 0.25‐ CONDITION: Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] Assessment of clinical improvement of critically ill patients with confirmed Covid‐19 by administering of sodium thiosulfate ; MedDRA version: 23.0 Level: PT Classification code 10084268 Term: COVID‐19 System Organ Class: 10021881 ‐ Infections and infestations PRIMARY OUTCOME: Secondary Objective: A secondary purpose is to describe data on the clinical efficacy of administration of up to three doses of STS in critically ill patients with confirmed COVID‐19.; Timepoint(s) of evaluation of this end point: Day 28 Main Objective: It has been described that in patients with critical COVID‐19 disease with ARDS in the Intensive Care Unit there is significant hydrogen sulfide (H2S) deficiency. H2S exerts significant anti‐inflammatory effects while competing with IL‐6. Sodium thiosulfate (STS) is a known H2S donor available for intravenous administration used for to treat cyanide poisoning and the side effects of cisplatin and is being investigated for its cardioprotective effect in patients with myocardial infarction. The aim of this study is to determine whether administration of sodium thiosulfate as a slow‐release hydrogen sulfide donor could improve the outcome of critically ill patients with confirmed COVID‐19.; ; Primary end point(s): Comparison of treatment‐emergent serious and non‐serious adverse events between treatment groups.; ; SECONDARY OUTCOME: Secondary end point(s): Comparison of treatment groups below:; ‐WHO‐CPS on day 7 from inclusion in the study; ‐WHO‐CPS on day 14 from inclusion in the study; ‐WHO‐CPS on day 28 of inclusion in the study; ‐Average value of the total SOFA score on day 7; ‐Hydrogen sulfide concentrations daily until day 7 in patient’s blood serum.; ‐Cytokine concentrations daily until day 7 in patient’s blood serum.; ‐Production of cytokines from mononuclear cells of patient’s blood on days 1,4 and 7; ; Timepoint(s) of evaluation of this end point: Day 7 ; Day 14 ; Day 28; Day 1‐7; Day 1,4,7 INCLUSION CRITERIA: ‐Age equal to or older than 18 years ‐Both genders ‐For women of childbearing potential, they must use or be willing to use a dual contraceptive method during the study. ‐Written consent statement provided by the patient or his / her legal representative in case patients are unable to consent. ‐Confirmed COVID‐19 disease ‐WHO‐CPS 7 to 9 ‐Hospitalization in Intensive Care Unit ‐Serum H2S levels less than 140 µM Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15