COVID-19, Infection Viral, Thromboses, Venous
Conditions
Brief summary
The purpose of this study is to evaluate the safety, dose-requirements, and exploratory efficacy of twice-daily subcutaneous enoxaparin as venous thromboembolism prophylaxis in children (birth to 18 years) hospitalized with signs and/or symptoms of SARS-CoV-2 infection (i.e., COVID-19).
Interventions
Twice-daily low-dose enoxaparin thromboprophylaxis (starting dose, 0.5 m/gkg subcutaneously q12 hours, adjusted to achieve a 4 hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL)
Sponsors
Johns Hopkins All Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Birth to \<18 years of age; AND 2. Positive nucleic acid test for SARS-CoV-2 within the past 7 days; AND 3. Hospitalized, \<72 hours post-admission; AND 4. One or more signs and/or symptoms of COVID-19 illness within the past 72 hours, as follows: 1. Cough; OR 2. Fever (oral temperature \>100.4°F/38°C); OR 3. Chest pain; OR 4. Shortness of breath; OR 5. Myalgia; OR 6. Acute unexplained loss of smell or taste; OR 7. New/increased supplemental oxygen requirement; OR 8. Acute respiratory failure requiring non-invasive or invasive ventilation; OR 9. Encephalitis.
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: 1. Receiving therapeutic anticoagulation for treatment of a thromboembolic event diagnosed within the past 12 weeks; OR 2. Clinical-relevant bleeding (see criteria under Primary Outcome, below) within the past 72 hours; OR 3. Platelet count \<50,000/µL within the past 24 hours; OR 4. Prothrombin time (PT) ≥2 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR 5. Activated partial thromboplastin time (aPTT) ≥4 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR 6. Fibrinogen level \<75 mg/dL; OR 7. Severe renal impairment, as defined by estimated glomerular filtration rate (eGFR) \<31 mL/min/ 1.73 m2, as calculated by the Schwartz formula; OR 8. Parent or legally authorized representative unwilling to provide informed consent for patient participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of In-hospital Thromboprophylaxis as Assessed by Number of Participants With ISTH-defined Clinically-relevant Bleeding Events During Hospitalization | Day 30 | The safety of in-hospital thromboprophylaxis with twice-daily low-dose enoxaparin thromboprophylaxis will be measured by cumulative incidence (number of participants) of ISTH-defined clinically-relevant bleeding events during hospitalization. Clinically relevant bleeding episodes may include any of the following: 1. fatal bleeding; 2. clinically overt bleeding associated with a decline in hemoglobin of ≥2g/dL in a 24h period; 3. retroperitoneal, pulmonary, or central nervous system bleeding; 4. bleeding requiring surgical intervention in an operating suite; 5. bleeding for which a blood product is administered (blood product administration not directly attributable to the patient's underlying condition); 6. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating suite. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Twice-daily Enoxaparin Dose Required to Achieve 4-hour Post-dose Anti-factor Xa Between 0.20-0.49 U/mL | 4 hours post initial dose | The median twice-daily enoxaparin dose, as measured in mg/kg, required to achieve a 4-hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL in children hospitalized with COVID-19, and to compare dose-requirements by age group (\<12 and those \>12 years of age). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of In-hospital Thromboprophylaxis as Measured by the Proportion of Serial D-dimer Levels | Enrollment, Day 1, Day 2, and Day 3, 7, and 14 if still hospitalized | To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by the proportion of serial D-dimer levels obtained at standardized time points that are \<2 times the upper limit of normal (\<2x ULN) values for age. |
| Efficacy of In-hospital Thromboprophylaxis as Measured by Number of Participants With Confirmed HA-VTE | Day 30 | To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by number of participants with confirmed HA-VTE. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thromboprophylaxis Twice-daily low-dose enoxaparin thromboprophylaxis (starting dose, 0.5 mg/kg subcutaneously q12 hours, adjusted to achieve a 4 hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL)
Enoxaparin Prefilled Syringe \[Lovenox\]: Twice-daily low-dose enoxaparin thromboprophylaxis (starting dose, 0.5 m/gkg subcutaneously q12 hours, adjusted to achieve a 4 hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL) | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet criteria for study intervention | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Thromboprophylaxis |
|---|---|
| Age, Categorical <=18 years | 38 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous Median Age (IQR) | 12.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 38 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 38 |
| other Total, other adverse events | 0 / 38 |
| serious Total, serious adverse events | 0 / 38 |
Outcome results
Primary
Safety of In-hospital Thromboprophylaxis as Assessed by Number of Participants With ISTH-defined Clinically-relevant Bleeding Events During Hospitalization
The safety of in-hospital thromboprophylaxis with twice-daily low-dose enoxaparin thromboprophylaxis will be measured by cumulative incidence (number of participants) of ISTH-defined clinically-relevant bleeding events during hospitalization. Clinically relevant bleeding episodes may include any of the following: 1. fatal bleeding; 2. clinically overt bleeding associated with a decline in hemoglobin of ≥2g/dL in a 24h period; 3. retroperitoneal, pulmonary, or central nervous system bleeding; 4. bleeding requiring surgical intervention in an operating suite; 5. bleeding for which a blood product is administered (blood product administration not directly attributable to the patient's underlying condition); 6. bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating suite.
Time frame: Day 30
Population: There were 19 \< 12 years of age and 19 \>/= 12 years of age.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Thromboprophylaxis | Safety of In-hospital Thromboprophylaxis as Assessed by Number of Participants With ISTH-defined Clinically-relevant Bleeding Events During Hospitalization | 0 Participants |
Secondary
Median Twice-daily Enoxaparin Dose Required to Achieve 4-hour Post-dose Anti-factor Xa Between 0.20-0.49 U/mL
The median twice-daily enoxaparin dose, as measured in mg/kg, required to achieve a 4-hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL in children hospitalized with COVID-19, and to compare dose-requirements by age group (\<12 and those \>12 years of age).
Time frame: 4 hours post initial dose
Population: Analysis was done based on division of participants into two groups: \< 12 years old and \>/= 12 years old.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Thromboprophylaxis | Median Twice-daily Enoxaparin Dose Required to Achieve 4-hour Post-dose Anti-factor Xa Between 0.20-0.49 U/mL | Children 12 years or older | 0.5 mg/kg |
| Thromboprophylaxis | Median Twice-daily Enoxaparin Dose Required to Achieve 4-hour Post-dose Anti-factor Xa Between 0.20-0.49 U/mL | Children less than 12 years | 0.52 mg/kg |
Other Pre-specified
Efficacy of In-hospital Thromboprophylaxis as Measured by Number of Participants With Confirmed HA-VTE
To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by number of participants with confirmed HA-VTE.
Time frame: Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Thromboprophylaxis | Efficacy of In-hospital Thromboprophylaxis as Measured by Number of Participants With Confirmed HA-VTE | 2 Participants |
Other Pre-specified
Efficacy of In-hospital Thromboprophylaxis as Measured by the Proportion of Serial D-dimer Levels
To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by the proportion of serial D-dimer levels obtained at standardized time points that are \<2 times the upper limit of normal (\<2x ULN) values for age.
Time frame: Enrollment, Day 1, Day 2, and Day 3, 7, and 14 if still hospitalized