Pharmacokinetics of Bivalirudin for Pediatric Anticoagulation

This study will measure plasma concentrations of bivalirudin in pediatric patients undergoing cardiac catheterization, cardiac surgical procedures utilizing cardiopulmonary bypass (CPB), or extracorporeal support with ECMO, ventricular support devices (VAD) or lung-assist devices (LAD). The aim is to understand the pharmacokinetics of bivalirudin in these settings.

Study Overview

• Status: Recruiting
• Conditions: Drug Effect
• Intervention / Treatment: Drug: Bivalirudin

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Zaleski L Zaleski, MD; Phone Number: 6173557737; Email: katherine.zaleski@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Recruiting
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric (age less than 18 years and more than 3kg) patients who present to Boston Children's Hospital (BCH) for cardiac catheterization, a cardiac surgical procedure utilizing CPB, or the institution of extracorporeal support and who require the administration of bivalirudin as part of their treatment plan will be included.

Description

Inclusion Criteria:

• pediatric patient (age less than 18 years)
• weight > 3kg
• scheduled to undergo 1) cardiac catheterization, 2)cardiac surgical procedure utilizing CPB, and/or 3) the institution of extracorporeal support
• must already require the administration of bivalirudin as part of their treatment plan

Exclusion Criteria:

• Age equal to or greater than 18 years,
• weight less than 3kg
• end-stage renal failure requiring renal replacement therapy.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric Cardiac Catheterization	Drug: Bivalirudin; CPB: Per hospital protocol, bivalirudin 1 mg/kg IV will be administered to the patient 10 minutes prior to the start of CPB along with an infusion of bivalirudin at 2.5 mg/kg/hr. Additional bolus doses of 0.5 to 1 mg/kg will be administered for ACTs less than the specified target (either 2 times baseline ACT or > 400 seconds per the discretion of the patient's providers). 50mg of bivalirudin will be administered to the bypass circuit. Cardiac Catheterization: Bivalirudin will be administered to the patient as 0.75mg/kg IV bolus followed by a 1.75mg/kg/hr infusion for the length of the procedure. Changes in infusion rate or bolus dosing during the procedure and post-procedure will be at the discretion of the patient's care providers. ECMO/VAD: Dosing will be informed by the hospital's formulary recommendations(http://online.lexi.com/lco/action/doc/retrieve/docid/chibos_f/6317841), but will ultimately be determined by patient's primary provider.
Pediatric Cardiac Surgery	Drug: Bivalirudin; CPB: Per hospital protocol, bivalirudin 1 mg/kg IV will be administered to the patient 10 minutes prior to the start of CPB along with an infusion of bivalirudin at 2.5 mg/kg/hr. Additional bolus doses of 0.5 to 1 mg/kg will be administered for ACTs less than the specified target (either 2 times baseline ACT or > 400 seconds per the discretion of the patient's providers). 50mg of bivalirudin will be administered to the bypass circuit. Cardiac Catheterization: Bivalirudin will be administered to the patient as 0.75mg/kg IV bolus followed by a 1.75mg/kg/hr infusion for the length of the procedure. Changes in infusion rate or bolus dosing during the procedure and post-procedure will be at the discretion of the patient's care providers. ECMO/VAD: Dosing will be informed by the hospital's formulary recommendations(http://online.lexi.com/lco/action/doc/retrieve/docid/chibos_f/6317841), but will ultimately be determined by patient's primary provider.
Pediatric Extracorporeal Life Support (ECLS)	Drug: Bivalirudin; CPB: Per hospital protocol, bivalirudin 1 mg/kg IV will be administered to the patient 10 minutes prior to the start of CPB along with an infusion of bivalirudin at 2.5 mg/kg/hr. Additional bolus doses of 0.5 to 1 mg/kg will be administered for ACTs less than the specified target (either 2 times baseline ACT or > 400 seconds per the discretion of the patient's providers). 50mg of bivalirudin will be administered to the bypass circuit. Cardiac Catheterization: Bivalirudin will be administered to the patient as 0.75mg/kg IV bolus followed by a 1.75mg/kg/hr infusion for the length of the procedure. Changes in infusion rate or bolus dosing during the procedure and post-procedure will be at the discretion of the patient's care providers. ECMO/VAD: Dosing will be informed by the hospital's formulary recommendations(http://online.lexi.com/lco/action/doc/retrieve/docid/chibos_f/6317841), but will ultimately be determined by patient's primary provider.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Bivalirudin Concentration	The primary end-point will be the plasma bivalirudin concentration (nanogram/mL) measured at multiple set time-points throughout the administration of bivalirudin in order to delineate the pharmacokinetic profile in the pediatric population.	Throughout the duration of treatment with bivalirudin and for one hour after the infusion is stopped. To be specific: 1. In CPB and cath lab cases arm: average 6 hours. 2. In ECLS arm: average 10 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
thrombotic complications	arterial, venous, and/or CPB/ECMO/VAD thrombosis; embolic stroke	Data will be assessed continuously in the procedural groups throughout the duration of the infusion and then continued weekly throughout the length of the hospital stay up to one year from enrollment.
bleeding in excess of expectations for a given procedure or ECLS modality		Data will be assessed continuously in the procedural groups throughout the duration of the infusion and then continued weekly throughout the length of the hospital stay up to one year from enrollment.
mortality		Data will be assessed continuously in the procedural groups throughout the duration of the infusion and then continued weekly throughout the length of the hospital stay or until death up to one year from enrollment.

Collaborators and Investigators

• Sponsor: Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2018
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: May 21, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 28, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Bivalirudin
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Antithrombins; Serine Proteinase Inhibitors; Bivalirudin
• Other Study ID Numbers: IRB-P00027930

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