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Phase 2 N=40 Randomized Quadruple-blind Treatment

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

ATIII Deficiency

Enrolled (actual)
40
Serious AEs
27.5%
Results posted
Jul 2017
Primary outcome: Primary: 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)

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Anti-thrombin III (Drug); Placebo (Other)
Age
Pediatric
Sex
All
Sponsor
Duke University
Primary completion
Jun 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
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)
SECONDARY
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)
SECONDARY
Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7
54; 54; 99; 49; 83; 55 0.982
SECONDARY
Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4
78.0; 69.0 0.048 sig
SECONDARY
Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7
1.1; 0.9; 0.6; 1.0; 1.3; 1.7 0.855
SECONDARY
Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.
0.1; 0.1
SECONDARY
Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group
SECONDARY
Total Dose of Heparin While on Cardiopulmonary Bypass
3775; 5000 0.056
SECONDARY
Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)
9.8; 10.0 0.545
SECONDARY
Total Volume of Blood Products While on CPB
57; 101.5; 68.5; 141.9; 89.7; 72.6
SECONDARY
Time From Protamine Administration to Skin Dressing
107.0; 89.0 0.757
SECONDARY
Total Volume of Fresh Frozen Plasma Given Prior to CPB
15; 5.8
SECONDARY
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
5; 5
SECONDARY
Volume of Postoperative Blood Loss
0.8; 2.8; 0; 2.7; 0; 2.1 0.2741
SECONDARY
Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters
59.0; 113.0 0.016 sig
SECONDARY
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group
1; 3; 0; 4; 0; 3
SECONDARY
Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group
6; 19 0.0004 sig
SECONDARY
Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively
56.1; 70.6 0.927
SECONDARY
Length of Post Operative Ventilation in Days
3.9; 3.6 0.738
SECONDARY
Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively
0; 2 0.231
SECONDARY
Incidence of Mediastinal Exploration Within 24 Hours Postoperatively
2; 3 0.661
SECONDARY
Incidence (Number) of Thrombotic Events Documented
0; 0
SECONDARY
Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria
1; 1 1.0
SECONDARY
Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage
1; 3 0.342
SECONDARY
Length of Time to Delayed Sternal Closure Measured in Days
2.7; 2.7 0.961

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.

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02103114). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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