Clinical Trial: Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Un

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 Summary:
Sponsor: Duke University

Current Primary Outcome: Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: Time 5 (on arrival in ICU) ]

Original Primary Outcome: Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: T4 (just prior to termination from CPB) ]

Current Secondary Outcome:

• Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: ICU arrival (Time 5) to Time 7 (Post OP (post-operative) Day 4) ]
  Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a 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 OP Day 4)
• Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: After initiation of bypass (Time 3) to Time 7 (Post OP Day 4) ]
  Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the ATIII (functional assay) and D dimer of the control and ATIII groups at Time 3-Time 7 (10min to 30min after initiation of CPB to Post OP Day 4).
• Total dose of heparin and protamine [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Total dose of heparin and protamine
• Total volume of blood products [ Time Frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) ]
  Total volume of blood products exposed intraoperatively including the pump prime (ml/kg)
• Time from protamine administration to skin dressing [ Time Frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) ]
  Time from protamine administration to skin dressing
• Volume of postoperative blood loss [ Time Frame: From 10min post protamine administration to 24 hour post protamine administration ]
  Volume of postoperative blood loss from 10min post protamine administration to 24 hour post protamine administration- (ml/kg)
• Volume of blood products [ Time Frame: From start of surgery to 24 hours post protamine administration ]
  Volume of packed Red blood cell, Fresh frozen plasma and cryoprecipitate transfused (ml/kg) from start of surgery to 24 hours post protamine administration
• Use of recombinant factor 7a (VIIa) [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Incidence of the use of rescue recombinant factor VIIa
• Length of post operative ventilation [ Time Frame: ICU arrival (Time 5) to Time 7 (Post OP Day 4) ]
  Length of post operative ventilation
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of extracorporeal membrane oxygenation (ECMO) support within 24 hours postoperatively.
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of mediastinal exploration within 24 hours postoperatively
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of thrombotic disease
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of renal disease
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of intracranial hemorrhage
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure

Original Secondary Outcome:

• Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: After initiation of bypass (T3), and ICU arrival (T5) to T7 (POD4) ]
  Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at times T3 (10min to 30min after initiation of CPB), T5-T7 (ICU arrival to Post OP Day 4)
• Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: After initiation of bypass (T3) to T7 (Post OP Day 4) ]
  Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the ATIII (functional assay), D dimer and TEG measurements of the control and ATIII groups at times T3-T7 (10min to 30min after initiation of CPB to Post OP Day 4).
• Total dose of heparin and protamine [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Total dose of heparin and protamine
• Total volume of blood products [ Time Frame: Baseline (intraoperatively) (T1) to before termination of bypass (T4) ]
  Total volume of blood products exposed intraoperatively including the pump prime (ml/kg)
• Time from protamine administration to skin dressing [ Time Frame: Baseline (intraoperatively) (T1) to before termination of bypass (T4) ]
  Time from protamine administration to skin dressing
• Volume of postoperative blood loss [ Time Frame: From 10min post protamine administration to 24h post protamine administration ]
  Volume of postoperative blood loss from 10min post protamine administration to 24h post protamine administration- (ml/kg)
• Volume of blood products [ Time Frame: From start of surgery to 24 hours post protamine administration ]
  Volume of packed Red blood cell, Fresh frozen plasma and cryoprecipitate transfused (ml/kg) from start of surgery to 24 hours post protamine administration
• Use of recombinant factor VIIa [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Incidence of the use of rescue recombinant factor VIIa
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of ECMO support within 24 hours postoperatively.
• Length of post operative ventilation [ Time Frame: ICU arrival (T5) to T7 (Post OP Day 4) ]
  Length of post operative ventilation
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of mediastinal exploration within 24 hours postoperatively
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of thrombotic disease
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of renal disease
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the incidence of intracranial hemorrhage
• Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (T1) to T7 (Post OP Day 4) ]
  Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure

Information By: Duke University

Dates:
Date Received: April 1, 2014
Date Started: June 2014
Date Completion:
Last Updated: November 29, 2016
Last Verified: November 2016