Antithrombin III in Infectious Disease Caused by COVID-19

Antithrombin III (AT3) in Infectious Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2)/ Coronavirus Disease of 2019 (COVID-19)

The purpose of this research study is to see if participants who have SARS-CoV-2 and low levels of AT3 in the blood will benefit by being given AT3.

Study Overview

• Status: Terminated
• Conditions: Covid19; Antithrombin III Deficiency
• Intervention / Treatment: Drug: Antithrombin III

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

1. >18y of age,
2. Subject or proxy who can provide informed consent
3. Positive SARS-COV-2 by Polymerase Chain Reaction (PCR) or as determined by clinical team

EXCLUSION CRITERIA:

1. Adults or Proxy unable to consent
2. Individuals who are not yet adults (infants, children, teenagers)
3. Pregnant women
4. Prisoners
5. Patients expected to die within 24 hours or with a "do not resuscitate" order,
6. Multi-organ failure,
7. History of hypersensitivity or allergy to any component of the study drug,
8. Ongoing massive surgical or unexplained bleeding,
9. History of bleeding or clotting disorder,
10. Severe traumatic brain injury (Glasgow Coma Scale <6),
11. Spinal or multiple-trauma,
12. Cancer (incurable/terminal phase) and/or patients receiving palliative care,
13. Enrollment in another concurrent clinical interventional study if considered interfering with this study objectives
14. Per study team discretion, any condition(s) that may prevent safe treatment, preclude adequate evaluation or adding further risk to their underlying illness.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AT3 less than 100% with SOC plus AT3 supplement; Participants in this group, with endogenous Antithrombin lll less than 100%, will receive 5 doses of supplemental Antithrombin III on Days 1, 3, 5, 7 and 9, in addition to standard of care (SOC) treatment.	Drug: Antithrombin III; Five total doses of daily 1,821 to 9,100 IUs Antithrombin III, depending on participant's weight, will be administered intravenously every other infusion day (Days 1, 3, 5, 7 and 9).; Other Names: Thrombate III
No Intervention: AT3 less than 100% with SOC only; Participants in this group, with endogenous Antithrombin III less than 100%, will receive SOC treatment only.
No Intervention: AT3 more than 100% with SOC only; Participants in this group, with endogenous Antithrombin III more than 100%, will receive SOC treatment only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ISTH DIC Score	As measured by the International Society of Thrombosis and Haemostasis Disseminated Intravascular Coagulation scale (ISTH DIC) which has a total score ranging from 0-8 with a score of 5 and higher indicating overt DIC.	Baseline, Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in D-Dimer Levels	D-Dimer levels assessed from blood samples will be evaluated in mcg/ml D-Dimer Units (DDU)	Baseline, Day 9
Change in Fibrinogen Levels	Fibrinogen levels assessed from blood samples will be evaluated in mg/dL.	Baseline, Day 9
Change in Prothrombin Time	Prothrombin time assessed from blood samples will be evaluated in seconds.	Baseline, Day 9
Length of Hospital Stay	Length of Hospital Stay reported in days.	Up to 60 days
Mortality Rate	The number of participants with reported death.	Up to 60 days
Pulmonary Function	Pulmonary Function will be reported as the mean days the participant was on any of the following: mechanical ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) use.	Up to 60 days
Change in SOFA Scores	Sequential Organ Failure Assessment (SOFA) is scored from 0-4 with the higher score indicating more organ failure.	Baseline, Day9
Change in SOFA Respiratory Sub Score	SOFA Respiratory Sub Score is scored from 0-4 with the higher score indicating worse organ failure.	Baseline, Day 9
Number of Events of Venous Thromboembolism	Number of events of venous thromboembolisms from admission to hospital discharge.	Up to 60 days
Number of Events of Major Bleeding	Number of events of major bleeding from admission to hospital discharge.	Up to 60 days

Collaborators and Investigators

• Sponsor: Enrique Ginzburg
• Collaborators: Grifols Biologicals, LLC
• Investigators: Principal Investigator: Enrique Ginzburg, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Genetic Diseases, Inborn; Blood Protein Disorders; Blood Coagulation Disorders; Thrombophilia; COVID-19; Infections; Communicable Diseases; Antithrombin III Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Antithrombins; Antithrombin III
• Other Study ID Numbers: 20201048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No