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

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).

Study Overview

• Status: Completed
• Conditions: COVID-19; Thromboses, Venous; Infection Viral
• Intervention / Treatment: Drug: Enoxaparin Prefilled Syringe [Lovenox]

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Sacramento, California, United States, 95817
      • Hemostasis and Thrombosis Center UC Davis
    • San Diego, California, United States, 92123
      • Rady Children's Hospital
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Hospital of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital and Children's Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • New York
    • New Hyde Park, New York, United States, 11040
      • Cohen Children's Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center of Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Enrollment, Day 1, Day 2, and Day 3, 7, and 14 if still hospitalized
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.	Day 30

Collaborators and Investigators

• Sponsor: Johns Hopkins All Children's Hospital
• Investigators: Principal Investigator: Anthony Sochet, MD, Johns Hopkins All Children's Hospital

Publications and helpful links

General Publications

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.
• Sochet AA, Morrison JM, Jaffray J, Godiwala N, Wilson HP, Thornburg CD, Bhat RV, Zia A, Lawrence C, Kudchadkar SR, Hamblin F, Russell CJ, Streiff MB, Spyropoulos AC, Amankwah EK, Goldenberg NA; COVID-19 Anticoagulation in Children - Thromboprophylaxis (COVAC-TP) Trial Investigators. Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial. Pediatrics. 2022 Jul 1;150(1):e2022056726. doi: 10.1542/peds.2022-056726.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 2, 2020
• Primary Completion (ACTUAL): June 4, 2021
• Study Completion (ACTUAL): June 4, 2021

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (ACTUAL): April 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Embolism and Thrombosis; COVID-19; Virus Diseases; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: COVAC-TP

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