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

Study Overview
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Brief Summary
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Pilot clinical trial, with a marketed drug -natural component of human plasma-, not approved for this indication, single-center, exploratory, open, randomized, controlled, to study the efficacy and safety of human Antithrombin in patients with confirmed COVID-19 disease and criteria high risk to develop SARS.

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

Conditions
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Covid19, Severe Acute Respiratory Syndrome, Distress Respiratory Syndrome

Intervention / Treatment
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* Drug: Antithrombin + best available treatment
* Drug: Best available treatment


Participation Criteria
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Eligibility Criteria
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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: Respiratory distress: Tachypnea > 26 breaths / minute PaO2 / FiO2 oxygenation index # 300 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Best available treatment + Antithrombin<br>The subject will be treated with Antithrombin (50 IU/Kg/12h) for 72 hours and the best available treatment for COVID-19. | Drug: Antithrombin + best available treatment<br>* The subject will be treated with Antithrombin (50 IU/Kg/12h) for 72 hours and the best available treatment for COVID-19.<br>|
| Active Comparator: Best available treatment<br>The subject will be treated with the best available treatment for COVID-19. | Drug: Best available treatment<br>* The subject will be treated with the best available treatment for COVID-19.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined variable: mortality or worsening rate with need for non-invasive mechanical ventilation or with need for invasive mechanical ventilation | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement (decreased risk of developing SARS or death) | 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. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Evaluate the improvement of the oxygenation index - PaO2 / FiO2- at 24 and 48 hours. | Evaluate the improvement of the oxygenation index - PaO2 / FiO2- at 24 and 48 hours. | 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. | 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) | 
| Time (in days) until improvement in oxygenation: - Time until the SpO2 / FiO2 ratio exceeds the worst SpO2 / FiO2 prior to AT treatment. | Time until the absence of oxygen need to maintain a basal saturation >= 92%. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Time to radiological improvement in radiological report. | Time to radiological improvement in radiological report. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Time (in days) of non-invasive mechanical ventilation. | Time (in days) of non-invasive mechanical ventilation. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Time (in days) of invasive mechanical ventilation. | Time (in days) of invasive mechanical ventilation. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Mortality rate in hospital and one month after pharmacological intervention. | Mortality rate in hospital and one month after pharmacological intervention. | One month after pharmacological intervention. | 
| Percentage of patients who suffer any adverse effect related to pharmacological intervention. | Percentage of patients who suffer any adverse effect related to pharmacological intervention. | One month after pharmacological intervention. | 
| Incidence of adverse events related to medication and its administration. | Incidence of adverse events related to medication and its administration. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Incidence in the appearance of allergic type hypersensitivity | Incidence in the appearance of Acne, Generalized urticaria, Chest tightness, Dyspnoea, Hypotension and/or Anaphylaxis. | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Incidence of B19 parvovirus infection | Incidence of B19 parvovirus infection | At day 31 after randomization or hospital discharge (whichever occurs first) | 
| Bleeding | Incidence of Bleeding | At day 31 after randomization or hospital discharge (whichever occurs first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antithrombin, COVID-19, Distress Respiratory Syndrome