Clinical trial NCT02103114: Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery
Official title: Double Blind Randomized Placebo-controlled Study in Children (<6mo) Comparing the Effects of Anti-thrombin III (ATIII) or Placebo on the Coagulation System in Infants With Known Low ATIII Levels Undergoing Open Congenital Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ATIII Deficiency
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Grifols Biologicals, LLC
First posted: 2014-04-03
Enrollment: 45
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test whether the administration of ATIII during the intra-operative period results in improved anticoagulation for cardiopulmonary bypass (CPB) and an attenuation of the activation of the coagulation cascade, as represented by a decrease in fibrin degradation products. The investigators believe this benefit would extend into the post-operative period resulting in a decreased incidence of thrombosis generation, as represented by a decrease in fibrin degradation products in the ICU period.

Detailed description: If Preoperative ATIII functional assay level is less than 70% patients would be enrolled and randomized to either Placebo (normal saline) or ATIII.

Eligibility criteria: Inclusion Criteria:

* All patients less than 7 months of age going for cardiac surgery that will require cardiopulmonary bypass (CPB) with a documented ATIII level below 70%

Exclusion Criteria:

* Less than 2.5kg
* Known or suspected hereditary ATIII deficiency (family history of venous thrombosis with decreased plasma levels of ATIII and no other potential causes of acquired decreased ATIII)
* On Ecmo (extracorporeal membrane oxygenation ) at time of surgery
* Known history of thrombosis
* Renal failure as described by the pediatric RIFLE criteria
* H/o intracranial hemorrhage
* Prematurity less than 37 weeks estimated gestational age
* Previously diagnosed pro-thrombotic or hemorrhagic disorder
* Prior ATIII supplementation
* Prior therapeutic anticoagulant use

Primary outcomes:
measure: Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU)
timeFrame: Time 5 (on arrival in ICU)
Secondary outcomes:
measure: Difference in the Mean and SD of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Times 5-Time 7 (ICU Arrival to Post Operative Day 4)
timeFrame: ICU arrival (Time 5) to Time 7 (Post-operative Day 4)
measure: Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7
timeFrame: T1, T2, T3, T5, T6 and T7
measure: Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4
timeFrame: T4 (just prior to coming off of CPB)
measure: Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7
timeFrame: T1, T5, T6 and T7
measure: Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.
timeFrame: T5 (Intensive Care Unit Arrival)
measure: Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group
timeFrame: Baseline (T1) to Post-Operative Day 4 (T7)
measure: Total Dose of Heparin While on Cardiopulmonary Bypass
timeFrame: T1 (Baseline) to T5 (Arrival in ICU)
measure: Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)
timeFrame: T1 (Baseline) to T5 (Arrival in ICU)
measure: Total Volume of Blood Products While on CPB
timeFrame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
measure: Time From Protamine Administration to Skin Dressing
timeFrame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
measure: Total Volume of Fresh Frozen Plasma Given Prior to CPB
timeFrame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
measure: Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
timeFrame: Baseline (Intraoperatively)
measure: Volume of Postoperative Blood Loss
timeFrame: From 10min post protamine administration to 24 hour post protamine administration
measure: Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters
timeFrame: protamine time plus 24 hours
measure: Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group
timeFrame: 24 Hours Post-Operatively
measure: Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group
timeFrame: 24 Hours Post-Operatively
measure: Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively
timeFrame: Intraoperatively
measure: Length of Post Operative Ventilation in Days
timeFrame: ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)
measure: Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively
timeFrame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
measure: Incidence of Mediastinal Exploration Within 24 Hours Postoperatively
timeFrame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
measure: Incidence (Number) of Thrombotic Events Documented
timeFrame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
measure: Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria
timeFrame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
measure: Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage
timeFrame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
measure: Length of Time to Delayed Sternal Closure Measured in Days
timeFrame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Edmund Jooste, MD
role: PRINCIPAL_INVESTIGATOR
References: