Antithrombin III Deficiency, Covid19
Conditions
Brief summary
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.
Interventions
DRUGAntithrombin 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).
Sponsors
Grifols Biologicals, LLC
Enrique Ginzburg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ISTH DIC Score | Baseline, Day 9 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fibrinogen Levels | Baseline, Day 9 | Fibrinogen levels assessed from blood samples will be evaluated in mg/dL. |
| Change in Prothrombin Time | Baseline, Day 9 | Prothrombin time assessed from blood samples will be evaluated in seconds. |
| Length of Hospital Stay | Up to 60 days | Length of Hospital Stay reported in days. |
| Mortality Rate | Up to 60 days | The number of participants with reported death. |
| Change in D-Dimer Levels | Baseline, Day 9 | D-Dimer levels assessed from blood samples will be evaluated in mcg/ml D-Dimer Units (DDU) |
| Change in SOFA Scores | Baseline, Day9 | Sequential Organ Failure Assessment (SOFA) is scored from 0-4 with the higher score indicating more organ failure. |
| Change in SOFA Respiratory Sub Score | Baseline, Day 9 | SOFA Respiratory Sub Score is scored from 0-4 with the higher score indicating worse organ failure. |
| Number of Events of Venous Thromboembolism | Up to 60 days | Number of events of venous thromboembolisms from admission to hospital discharge. |
| Number of Events of Major Bleeding | Up to 60 days | Number of events of major bleeding from admission to hospital discharge. |
| Pulmonary Function | Up to 60 days | 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. |
Countries
United States
Participant flow
Pre-assignment details
Participant death while on the study is considered completion of study.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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). | 20 |
| AT3 Less Than 100% With SOC Only Participants in this group, with endogenous Antithrombin III less than 100%, will receive SOC treatment only. | 20 |
| AT3 More Than 100% With SOC Only Participants in this group, with endogenous Antithrombin III more than 100%, will receive SOC treatment only. | 12 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Screening Period | Participant discharged before receiving intervention | 3 | 0 | 0 |
| Screening Period | Physician Decision | 1 | 0 | 0 |
| Screening Period | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | AT3 Less Than 100% With SOC Plus AT3 Supplement | AT3 Less Than 100% With SOC Only | AT3 More Than 100% With SOC Only | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 3 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 14 Participants | 9 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 14 Participants | 7 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 6 Participants | 5 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 5 Participants | 4 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 14 Participants | 8 Participants | 34 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 8 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 15 | 3 / 20 | 3 / 12 |
| other Total, other adverse events | 5 / 15 | 5 / 20 | 8 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 20 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline, Day 9
Population: Not all participants were able to complete the assessments required for evaluation of the DIC score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Change in ISTH DIC Score | 0.27 score on a scale | Standard Deviation 1.71 |
| AT3 Less Than 100% With SOC Only | Change in ISTH DIC Score | 0 score on a scale | Standard Deviation 1.73 |
| AT3 More Than 100% With SOC Only | Change in ISTH DIC Score | 0 score on a scale | Standard Deviation 1.65 |
Secondary
Change in D-Dimer Levels
D-Dimer levels assessed from blood samples will be evaluated in mcg/ml D-Dimer Units (DDU)
Time frame: Baseline, Day 9
Population: Not all participants were able to complete the assessments required for the evaluation of the D-dimer.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Change in D-Dimer Levels | -1.97 mcg/ml DDU | Standard Deviation 5.6 |
| AT3 Less Than 100% With SOC Only | Change in D-Dimer Levels | 0.4 mcg/ml DDU | Standard Deviation 3.18 |
| AT3 More Than 100% With SOC Only | Change in D-Dimer Levels | 0.25 mcg/ml DDU | Standard Deviation 2.18 |
Secondary
Change in Fibrinogen Levels
Fibrinogen levels assessed from blood samples will be evaluated in mg/dL.
Time frame: Baseline, Day 9
Population: Not all participants were able to complete the assessments required for evaluation of Fibrinogen levels.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Change in Fibrinogen Levels | -102.1 mg/dL | Standard Deviation 233.7 |
| AT3 Less Than 100% With SOC Only | Change in Fibrinogen Levels | -123 mg/dL | Standard Deviation 215.1 |
| AT3 More Than 100% With SOC Only | Change in Fibrinogen Levels | -111 mg/dL | Standard Deviation 307.5 |
Secondary
Change in Prothrombin Time
Prothrombin time assessed from blood samples will be evaluated in seconds.
Time frame: Baseline, Day 9
Population: Not all participants were able to complete the assessments required for evaluation of the Prothrombin Time levels.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Change in Prothrombin Time | 0.01 Seconds | Standard Deviation 2.07 |
| AT3 Less Than 100% With SOC Only | Change in Prothrombin Time | 0.31 Seconds | Standard Deviation 1.27 |
| AT3 More Than 100% With SOC Only | Change in Prothrombin Time | 0.59 Seconds | Standard Deviation 1.39 |
Secondary
Change in SOFA Respiratory Sub Score
SOFA Respiratory Sub Score is scored from 0-4 with the higher score indicating worse organ failure.
Time frame: Baseline, Day 9
Population: Not all participants were able to complete the assessments required for evaluation of the SOFA sub score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Change in SOFA Respiratory Sub Score | -0.67 score on a scale | Standard Deviation 0.98 |
| AT3 Less Than 100% With SOC Only | Change in SOFA Respiratory Sub Score | -0.07 score on a scale | Standard Deviation 0.7 |
| AT3 More Than 100% With SOC Only | Change in SOFA Respiratory Sub Score | -0.17 score on a scale | Standard Deviation 1.69 |
Secondary
Change in SOFA Scores
Sequential Organ Failure Assessment (SOFA) is scored from 0-4 with the higher score indicating more organ failure.
Time frame: Baseline, Day9
Population: Not all participants were able to complete the assessments required for evaluation of the SOFA score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Change in SOFA Scores | 0.43 score on a scale | Standard Deviation 3.41 |
| AT3 Less Than 100% With SOC Only | Change in SOFA Scores | 1.23 score on a scale | Standard Deviation 3.33 |
| AT3 More Than 100% With SOC Only | Change in SOFA Scores | 0.64 score on a scale | Standard Deviation 2.27 |
Secondary
Length of Hospital Stay
Length of Hospital Stay reported in days.
Time frame: Up to 60 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Length of Hospital Stay | 13 Days | Standard Deviation 15.1 |
| AT3 Less Than 100% With SOC Only | Length of Hospital Stay | 6 Days | Standard Deviation 8.35 |
| AT3 More Than 100% With SOC Only | Length of Hospital Stay | 8.5 Days | Standard Deviation 9.46 |
Secondary
Mortality Rate
The number of participants with reported death.
Time frame: Up to 60 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Mortality Rate | 2 Participants |
| AT3 Less Than 100% With SOC Only | Mortality Rate | 3 Participants |
| AT3 More Than 100% With SOC Only | Mortality Rate | 3 Participants |
Secondary
Number of Events of Major Bleeding
Number of events of major bleeding from admission to hospital discharge.
Time frame: Up to 60 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Number of Events of Major Bleeding | 0 events |
| AT3 Less Than 100% With SOC Only | Number of Events of Major Bleeding | 0 events |
| AT3 More Than 100% With SOC Only | Number of Events of Major Bleeding | 2 events |
Secondary
Number of Events of Venous Thromboembolism
Number of events of venous thromboembolisms from admission to hospital discharge.
Time frame: Up to 60 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Number of Events of Venous Thromboembolism | 0 Events |
| AT3 Less Than 100% With SOC Only | Number of Events of Venous Thromboembolism | 0 Events |
| AT3 More Than 100% With SOC Only | Number of Events of Venous Thromboembolism | 3 Events |
Secondary
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.
Time frame: Up to 60 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT3 Less Than 100% With SOC Plus AT3 Supplement | Pulmonary Function | 1.33 Days | Standard Deviation 5.16 |
| AT3 Less Than 100% With SOC Only | Pulmonary Function | 2.2 Days | Standard Deviation 6.7 |
| AT3 More Than 100% With SOC Only | Pulmonary Function | 3.08 Days | Standard Deviation 6.97 |