Pilot Study of Antithrombin as Prophylaxis of Acute Respiratory Distress Syndrome in Patients With COVID-19

• Antithrombin + best available treatment (Drug): The subject will be treated with Antithrombin (50 IU/Kg/12h) for 72 hours and the best available treatment for COVID-19.
• Best available treatment (Drug): The subject will be treated with the best available treatment for COVID-19.

Primary outcomes

• Combined variable: mortality or worsening rate with need for non-invasive mechanical ventilation or with need for invasive mechanical ventilation [At day 31 after randomization or hospital discharge (whichever occurs first)]: Combined variable: mortality or worsening rate with need for non-invasive mechanical ventilation or with need for invasive mechanical ventilation

Secondary outcomes

• Time to clinical improvement (decreased risk of developing SARS or death) [At day 31 after randomization or hospital discharge (whichever occurs first)]: Time (in days) to improvement in the National Early Warning (NEWS) Score 2. Defined as the time, in days, from the start of treatment a two-point improvement on this scale.
• Evaluate the improvement of the oxygenation index - PaO2 / FiO2- at 24 and 48 hours. [At 24 and 48 hours.]: Evaluate the improvement of the oxygenation index - PaO2 / FiO2- at 24 and 48 hours.
• Improvement of the analytical parameters: time (in days) until the tendency to normalization (decrease >= 20%) of DD, ferritin, LDH, PCR and IL-6; the criteria reached before will be used. [At day 31 after randomization or hospital discharge (whichever occurs first)]: Improvement of the analytical parameters: time (in days) until the tendency to normalization (decrease >= 20%) of DD, ferritin, LDH, PCR and IL-6; the criteria reached before will be used.
• Time (in days) until improvement in oxygenation: - Time until the SpO2 / FiO2 ratio exceeds the worst SpO2 / FiO2 prior to AT treatment. [At day 31 after randomization or hospital discharge (whichever occurs first)]: Time until the absence of oxygen need to maintain a basal saturation >= 92%.
• Time to radiological improvement in radiological report. [At day 31 after randomization or hospital discharge (whichever occurs first)]: Time to radiological improvement in radiological report.
• Time (in days) of non-invasive mechanical ventilation. [At day 31 after randomization or hospital discharge (whichever occurs first)]: Time (in days) of non-invasive mechanical ventilation.
• Time (in days) of invasive mechanical ventilation. [At day 31 after randomization or hospital discharge (whichever occurs first)]: Time (in days) of invasive mechanical ventilation.
• Mortality rate in hospital and one month after pharmacological intervention. [One month after pharmacological intervention.]: Mortality rate in hospital and one month after pharmacological intervention.
• Percentage of patients who suffer any adverse effect related to pharmacological intervention. [One month after pharmacological intervention.]: Percentage of patients who suffer any adverse effect related to pharmacological intervention.
• Incidence of adverse events related to medication and its administration. [At day 31 after randomization or hospital discharge (whichever occurs first)]: Incidence of adverse events related to medication and its administration.
• Incidence in the appearance of allergic type hypersensitivity [At day 31 after randomization or hospital discharge (whichever occurs first)]: Incidence in the appearance of Acne, Generalized urticaria, Chest tightness, Dyspnoea, Hypotension and/or Anaphylaxis.
• Incidence of B19 parvovirus infection [At day 31 after randomization or hospital discharge (whichever occurs first)]: Incidence of B19 parvovirus infection
• Bleeding [At day 31 after randomization or hospital discharge (whichever occurs first)]: Incidence of Bleeding

Sex: All, ages: 18 Years to 85 Years

Inclusion Criteria:

* Age >= 18 and < 85 years
* COVID-19 diagnosis confirmed.
* Radiological image compatible with COVID-19
* Present any of the following clinical-functional criteria considered RISK:

  1. Respiratory distress: Tachypnea > 26 breaths / minute
  2. PaO2 / FiO2 oxygenation index # 300
  3. Alteration of one or more of the following parameters:

  c.i. DD> 1,000 µg / L c.ii. Ferritin> 800 ng / mL 4.c.iii. Lymphocytes <800 cells / µL 4.c.iv. PCR> 100 mg / L 4.c.v. LDH> 500 U / L c.vi. IL-6> 15 pg / mL
* Direct or delegated verbal informed consent

Exclusion Criteria:

* Signs of active bleeding
* Immunosuppression by cancer or transplant
* Intolerance or allergy to AT or its components
* Pregnancy

• Ángel Salvatierra, MD, Principal investigator, Hospital General Universitario Reina Sofía de Murcia