Pharmacokinetics of Bivalirudin for Pediatric Anticoagulation

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Pharmacokinetics of Bivalirudin for Pediatric Anticoagulation

Conditions
-----------------
Drug Effect

Intervention / Treatment
-----------------
* Drug: Bivalirudin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric Cardiac Catheterization<br> | Drug: Bivalirudin<br>* 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.<br>|
| Pediatric Cardiac Surgery<br> | Drug: Bivalirudin<br>* 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.<br>|
| Pediatric Extracorporeal Life Support (ECLS)<br> | Drug: Bivalirudin<br>* 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.<br>|

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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bivalirudin