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

Sponsor
Johns Hopkins All Children's Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT04354155
Collaborator
(none)
40
16
1
12.1
2.5
0.2

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
  • Drug: Enoxaparin Prefilled Syringe [Lovenox]
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
COVID-19 Anticoagulation in Children - Thromboprophlaxis (COVAC-TP) Trial
Actual Study Start Date :
Jun 2, 2020
Actual Primary Completion Date :
Jun 4, 2021
Actual Study Completion Date :
Jun 4, 2021

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

  1. 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

  1. 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

  1. 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.

  2. 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

Ages Eligible for Study:
0 Years to 18 Years
Sexes Eligible for Study:
All
Accepts 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:

  5. Cough; OR

  6. Fever (oral temperature >100.4°F/38°C); OR

  7. Chest pain; OR

  8. Shortness of breath; OR

  9. Myalgia; OR

  10. Acute unexplained loss of smell or taste; OR

  11. New/increased supplemental oxygen requirement; OR

  12. Acute respiratory failure requiring non-invasive or invasive ventilation; OR

  13. 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.

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.
Responsible Party:
Johns Hopkins All Children's Hospital
ClinicalTrials.gov Identifier:
NCT04354155
Other Study ID Numbers:
  • COVAC-TP
First Posted:
Apr 21, 2020
Last Update Posted:
Apr 1, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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
3. Other Pre-specified Outcome
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
4. Other Pre-specified Outcome
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

[Not Specified]

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
Email anthony.sochet@jhmi.edu
Responsible Party:
Johns Hopkins All Children's Hospital
ClinicalTrials.gov Identifier:
NCT04354155
Other Study ID Numbers:
  • COVAC-TP
First Posted:
Apr 21, 2020
Last Update Posted:
Apr 1, 2022
Last Verified:
Mar 1, 2022