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

• ClinicalTrials.gov Identifier: NCT04354155
• Recruitment Status: Completed
• First Posted: April 21, 2020
• Results First Posted: March 31, 2022
• Last Update Posted: April 1, 2022
• Sponsor: Johns Hopkins All Children's Hospital
• Information provided by (Responsible Party): Johns Hopkins All Children's Hospital

Tracking Information

• First Submitted Date: April 13, 2020
• First Posted Date: April 21, 2020
• Results First Submitted Date: March 1, 2022
• Results First Posted Date: March 31, 2022
• Last Update Posted Date: April 1, 2022
• Actual Study Start Date: June 2, 2020
• Actual Primary Completion Date: June 4, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2022)

Safety of In-hospital Thromboprophylaxis as Assessed by Number of Participants With ISTH-defined Clinically-relevant Bleeding Events During Hospitalization [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 16, 2020)

Safety of in-hospital thromboprophylaxis [ Time Frame: Day 30 ]

To investigate the safety of in-hospital thromboprophylaxis with twice-daily low-dose enoxaparin thromboprophylaxis as measured by cumulative incidence 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.

Current Secondary Outcome Measures (submitted: March 1, 2022)

Median Twice-daily Enoxaparin Dose Required to Achieve 4-hour Post-dose Anti-factor Xa Between 0.20-0.49 U/mL [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: April 16, 2020)

Median twice-daily enoxaparin dose [ Time Frame: 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 (birth to <1 year old, 1-<6 years old, 6-<13 years old, and 13-<18 years old).

Current Other Pre-specified Outcome Measures (submitted: March 1, 2022)

• Efficacy of In-hospital Thromboprophylaxis as Measured by the Proportion of Serial D-dimer Levels [ Time Frame: 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 [ Time Frame: 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.

Original Other Pre-specified Outcome Measures (submitted: April 16, 2020)

• Efficacy of in-hospital thromboprophylaxis as measured by the proportion of serial D-dimer levels [ Time Frame: 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 confirmed HA-VTE [ Time Frame: 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 confirmed HA-VTE.
• Efficacy of in-hospital thromboprophylaxis as measured by median duration of increased respiratory support [ Time Frame: 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 median duration of in-hospital increased respiratory support (new requirement for high-flow nasal cannula, non-invasive ventilation, and/or mechanical ventilation, relative to any at-home baseline requirement).

Descriptive Information

• Brief Title: COVID-19 Anticoagulation in Children - Thromboprophlaxis (COVAC-TP) Trial
• Official Title: COVID-19 Anticoagulation in Children - Thromboprophlaxis (COVAC-TP) Trial
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Infection Viral
• Thromboses, Venous
• COVID-19

Intervention

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)

Study Arms

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)

Intervention: Drug: Enoxaparin Prefilled Syringe [Lovenox]

Publications *

• Flumignan RL, Civile VT, Tinôco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah ÁN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3:CD013739. doi: 10.1002/14651858.CD013739.pub2. Review.
• Flumignan RL, Tinôco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah ÁN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10:CD013739. doi: 10.1002/14651858.CD013739. Update in: Cochrane Database Syst Rev. 2022 Mar 4;3:CD013739.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 19, 2021): 40
• Original Estimated Enrollment (submitted: April 16, 2020): 38
• Actual Study Completion Date: June 4, 2021
• Actual Primary Completion Date: June 4, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04354155
• Other Study ID Numbers: COVAC-TP
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Johns Hopkins All Children's Hospital
• Original Responsible Party: Neil Goldenberg, Johns Hopkins All Children's Hospital, Sponsor-investigator
• Current Study Sponsor: Johns Hopkins All Children's Hospital
• Original Study Sponsor: Neil Goldenberg
• Collaborators: Not Provided

Investigators

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

• PRS Account: Johns Hopkins All Children's Hospital
• Verification Date: March 2022