COVID-19 Anticoagulation in Children - Thromboprophlaxis (COVAC-TP) Trial
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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) |
Drug: 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)
|
Outcome Measures
Primary Outcome Measures
- 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: fatal bleeding; clinically overt bleeding associated with a decline in hemoglobin of ≥2g/dL in a 24h period; retroperitoneal, pulmonary, or central nervous system bleeding; bleeding requiring surgical intervention in an operating suite; bleeding for which a blood product is administered (blood product administration not directly attributable to the patient's underlying condition); bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating suite.
Secondary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Birth to <18 years of age; AND
-
Positive nucleic acid test for SARS-CoV-2 within the past 7 days; AND
-
Hospitalized, <72 hours post-admission; AND
-
One or more signs and/or symptoms of COVID-19 illness within the past 72 hours, as follows:
-
Cough; OR
-
Fever (oral temperature >100.4°F/38°C); OR
-
Chest pain; OR
-
Shortness of breath; OR
-
Myalgia; OR
-
Acute unexplained loss of smell or taste; OR
-
New/increased supplemental oxygen requirement; OR
-
Acute respiratory failure requiring non-invasive or invasive ventilation; OR
-
Encephalitis.
Exclusion Criteria:
An individual who meets any of the following criteria will be excluded from participation in this study:
-
Receiving therapeutic anticoagulation for treatment of a thromboembolic event diagnosed within the past 12 weeks; OR
-
Clinical-relevant bleeding (see criteria under Primary Outcome, below) within the past 72 hours; OR
-
Platelet count <50,000/µL within the past 24 hours; OR
-
Prothrombin time (PT) ≥2 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR
-
Activated partial thromboplastin time (aPTT) ≥4 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR
-
Fibrinogen level <75 mg/dL; OR
-
Severe renal impairment, as defined by estimated glomerular filtration rate (eGFR) <31 mL/min/ 1.73 m2, as calculated by the Schwartz formula; OR
-
Parent or legally authorized representative unwilling to provide informed consent for patient participation.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Children's of Alabama | Birmingham | Alabama | United States | 35233 |
2 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
3 | Hemostasis and Thrombosis Center UC Davis | Sacramento | California | United States | 95817 |
4 | Rady Children's Hospital | San Diego | California | United States | 92123 |
5 | Johns Hopkins All Children's Hospital | Saint Petersburg | Florida | United States | 33701 |
6 | Children's Hospital of Atlanta | Atlanta | Georgia | United States | 30322 |
7 | Lurie Children's Hospital | Chicago | Illinois | United States | 60611 |
8 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
9 | Children's Hospital New Orleans | New Orleans | Louisiana | United States | 70118 |
10 | Johns Hopkins Hospital and Children's Center | Baltimore | Maryland | United States | 21287 |
11 | Boston Children's Hospital | Boston | Massachusetts | United States | 02115 |
12 | Children's Hospital of Michigan | Detroit | Michigan | United States | 48201 |
13 | Cohen Children's Medical Center | New Hyde Park | New York | United States | 11040 |
14 | Akron Children's Hospital | Akron | Ohio | United States | 44308 |
15 | Children's Hospital Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
16 | Children's Medical Center of Dallas | Dallas | Texas | United States | 75235 |
Sponsors and Collaborators
- Johns Hopkins All Children's Hospital
Investigators
- Principal Investigator: Anthony Sochet, MD, Johns Hopkins All Children's Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.- COVAC-TP
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Thromboprophylaxis |
---|---|
Arm/Group Description | 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) |
Period Title: Overall Study | |
STARTED | 40 |
COMPLETED | 38 |
NOT COMPLETED | 2 |
Baseline Characteristics
Arm/Group Title | Thromboprophylaxis |
---|---|
Arm/Group Description | 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) |
Overall Participants | 38 |
Age (Count of Participants) | |
<=18 years |
38
100%
|
Between 18 and 65 years |
0
0%
|
>=65 years |
0
0%
|
Age (years) [Median (Inter-Quartile Range) ] | |
Median Age (IQR) |
12.1
|
Sex: Female, Male (Count of Participants) | |
Female |
18
47.4%
|
Male |
20
52.6%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
12
31.6%
|
Not Hispanic or Latino |
25
65.8%
|
Unknown or Not Reported |
1
2.6%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
1
2.6%
|
Native Hawaiian or Other Pacific Islander |
1
2.6%
|
Black or African American |
12
31.6%
|
White |
16
42.1%
|
More than one race |
1
2.6%
|
Unknown or Not Reported |
7
18.4%
|
Region of Enrollment (Count of Participants) | |
United States |
38
100%
|
Outcome Measures
Title | Safety of In-hospital Thromboprophylaxis as Assessed by Number of Participants With ISTH-defined Clinically-relevant Bleeding Events During Hospitalization |
---|---|
Description | 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: fatal bleeding; clinically overt bleeding associated with a decline in hemoglobin of ≥2g/dL in a 24h period; retroperitoneal, pulmonary, or central nervous system bleeding; bleeding requiring surgical intervention in an operating suite; bleeding for which a blood product is administered (blood product administration not directly attributable to the patient's underlying condition); bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating suite. |
Time Frame | Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
There were 19 < 12 years of age and 19 >/= 12 years of age. |
Arm/Group Title | Thromboprophylaxis |
---|---|
Arm/Group Description | 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) |
Measure Participants | 38 |
Count of Participants [Participants] |
0
0%
|
Title | Median Twice-daily Enoxaparin Dose Required to Achieve 4-hour Post-dose Anti-factor Xa Between 0.20-0.49 U/mL |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was done based on division of participants into two groups: < 12 years old and >/= 12 years old. |
Arm/Group Title | Thromboprophylaxis |
---|---|
Arm/Group Description | 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) |
Measure Participants | 38 |
Children 12 years or older |
0.5
|
Children less than 12 years |
0.52
|
Title | Efficacy of In-hospital Thromboprophylaxis as Measured by the Proportion of Serial D-dimer Levels |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Efficacy of In-hospital Thromboprophylaxis as Measured by Number of Participants With Confirmed HA-VTE |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Thromboprophylaxis |
---|---|
Arm/Group Description | 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) |
Measure Participants | 38 |
Count of Participants [Participants] |
2
5.3%
|
Adverse Events
Time Frame | From enrollment through follow up, up to 30 days after enrollment. | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Thromboprophylaxis | |
Arm/Group Description | 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) | |
All Cause Mortality |
||
Thromboprophylaxis | ||
Affected / at Risk (%) | # Events | |
Total | 1/38 (2.6%) | |
Serious Adverse Events |
||
Thromboprophylaxis | ||
Affected / at Risk (%) | # Events | |
Total | 0/38 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Thromboprophylaxis | ||
Affected / at Risk (%) | # Events | |
Total | 0/38 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Anthony Alexander Sochet |
---|---|
Organization | Johns Hopkins All Children's Hospital |
Phone | 17277672912 |
anthony.sochet@jhmi.edu |
- COVAC-TP