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

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.

Study Overview

• Status: Completed
• Conditions: Severe Acute Respiratory Syndrome; Covid19; Distress Respiratory Syndrome
• Intervention / Treatment: Drug: Antithrombin + best available treatment; Drug: Best available treatment

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Investigators: Principal Investigator: Ángel Salvatierra, MD, Hospital Universitario Reina Sofia

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): December 20, 2020
• Study Completion (Actual): January 15, 2021

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Antithrombin; Distress Respiratory Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: ANTITROMBINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: The information will be provided after the results are published in a journal.
• IPD Sharing Access Criteria: Upon request to uicec@imibic.org
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No