COVID-19 Anticoagulation in Children - Thromboprophlaxis (COVAC-TP) Trial

Study Overview
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Brief Summary
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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).

Official Title
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COVID-19 Anticoagulation in Children - Thromboprophlaxis (COVAC-TP) Trial

Conditions
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Infection Viral, Thromboses, Venous, COVID-19

Intervention / Treatment
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* Drug: Enoxaparin Prefilled Syringe [Lovenox]


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thromboprophylaxis<br>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]<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: 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. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 4 hours post initial dose |