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

• ClinicalTrials.gov Identifier: NCT04745442
• Recruitment Status: Completed
• First Posted: February 9, 2021
• Last Update Posted: February 9, 2021
• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Information provided by (Responsible Party): Maimónides Biomedical Research Institute of Córdoba

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid19; Severe Acute Respiratory Syndrome; Distress Respiratory Syndrome	Drug: Antithrombin + best available treatment; Drug: Best available treatment	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Antithrombin as Prophylaxis of Acute Respiratory Distress Syndrome in Patients With COVID-19
• Actual Study Start Date: April 27, 2020
• Actual Primary Completion Date: December 20, 2020
• Actual Study Completion Date: January 15, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Combined variable: mortality or worsening rate with need for non-invasive mechanical ventilation or with need for invasive mechanical ventilation [ Time Frame: 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 Outcome Measures :

1. Time to clinical improvement (decreased risk of developing SARS or death) [ Time Frame: 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.
2. Evaluate the improvement of the oxygenation index - PaO2 / FiO2- at 24 and 48 hours. [ Time Frame: At 24 and 48 hours. ]
   Evaluate the improvement of the oxygenation index - PaO2 / FiO2- at 24 and 48 hours.
3. 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 Frame: 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.
4. Time (in days) until improvement in oxygenation: - Time until the SpO2 / FiO2 ratio exceeds the worst SpO2 / FiO2 prior to AT treatment. [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
   Time until the absence of oxygen need to maintain a basal saturation >= 92%.
5. Time to radiological improvement in radiological report. [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
   Time to radiological improvement in radiological report.
6. Time (in days) of non-invasive mechanical ventilation. [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
   Time (in days) of non-invasive mechanical ventilation.
7. Time (in days) of invasive mechanical ventilation. [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
   Time (in days) of invasive mechanical ventilation.
8. Mortality rate in hospital and one month after pharmacological intervention. [ Time Frame: One month after pharmacological intervention. ]
   Mortality rate in hospital and one month after pharmacological intervention.
9. Percentage of patients who suffer any adverse effect related to pharmacological intervention. [ Time Frame: One month after pharmacological intervention. ]
   Percentage of patients who suffer any adverse effect related to pharmacological intervention.
10. Incidence of adverse events related to medication and its administration. [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
    Incidence of adverse events related to medication and its administration.
11. Incidence in the appearance of allergic type hypersensitivity [ Time Frame: 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.
12. Incidence of B19 parvovirus infection [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
    Incidence of B19 parvovirus infection
13. Bleeding [ Time Frame: At day 31 after randomization or hospital discharge (whichever occurs first) ]
    Incidence of Bleeding

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Spain

Hospital Universitario Reina Sofía

Córdoba, Spain, 14004

Sponsors and Collaborators

Maimónides Biomedical Research Institute of Córdoba

Investigators

• Principal Investigator: Ángel Salvatierra, MD; Hospital Universitario Reina Sofía

More Information

• Responsible Party: Maimónides Biomedical Research Institute of Córdoba
• ClinicalTrials.gov Identifier: NCT04745442
• Other Study ID Numbers: ANTITROMBINA
• First Posted: February 9, 2021
• Last Update Posted: February 9, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: The information will be provided after the results are published in a journal.
• Access Criteria: Upon request to uicec@imibic.org

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maimónides Biomedical Research Institute of Córdoba:

Antithrombin; COVID-19; Distress Respiratory Syndrome

Additional relevant MeSH terms:

COVID-19; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Disease; Pathologic Processes; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Antithrombins; Antithrombin III; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants