Trial record 5 of 6 for:    "antithrombin deficiency"

Anti-thrombin III (ATIII) vs Placebo in Children (<6mo) Undergoing Open Congenital Cardiac Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Duke University
Sponsor:
Collaborator:
Grifols Biologicals Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT02103114
First received: April 1, 2014
Last updated: July 21, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
ATIII Deficiency
Drug: Anti-thrombin III
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: Time 4 (just prior to termination from CPB) ] [ Designated as safety issue: No ]
    Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at Time 4 (just prior to termination from CPB approximately 5 to 15 minutes prior to CPB termination ).


Secondary Outcome Measures:
  • Decreased activation of the coagulation and fibrinolytic systems [ Time Frame: After initiation of bypass (Time 3), and ICU arrival (Time 5) to Time 7 (Post OP (post-operative) Day 4) ] [ Designated as safety issue: No ]
    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 Time 3 (10min to 30min after initiation of CPB), Time 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) ] [ Designated as safety issue: No ]
    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 thromboelastogram (TEG) measurements 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) ] [ Designated as safety issue: No ]
    Total dose of heparin and protamine

  • Total volume of blood products [ Time Frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Incidence of the use of rescue recombinant factor VIIa

  • Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ] [ Designated as safety issue: No ]
    Study the safety profile of dosing the ATIII by monitoring the incidence of extracorporeal membrane oxygenation (ECMO) support within 24 hours postoperatively.

  • Length of post operative ventilation [ Time Frame: ICU arrival (Time 5) to Time 7 (Post OP Day 4) ] [ Designated as safety issue: No ]
    Length of post operative ventilation

  • Safety profile of ATIII dosing [ Time Frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure


Estimated Enrollment: 40
Study Start Date: June 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anti-thrombin III Drug: Anti-thrombin III
  • If the Activated clotting time (ACT) is below the goal of 480 seconds the patient will first be given an additional dose of 200u/kg of heparin. If the patient's ACT remains below 480 seconds, they will be given 20ml/kg of Fresh Frozen Plasma (FFP). The above dose of heparin and FFP will be repeated until an ACT of greater than 480 seconds is achieved.
  • If Preoperative ATIII functional assay level is less than 70% - patients would be enrolled and randomized to either Placebo (normal saline) or ATIII. Intraoperatively- (correcting to 100%) according to the following formula:

Units required = ((100%- baseline ATIII level*%) X body weight)/1.4

  • expressed as a % normal level based on functional ATIII assay
Other Name: Thrombate III
Other: Placebo
Normal saline placebo
Placebo Comparator: Placebo

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients less than 6 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02103114

Locations
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27708
Contact: Angelo Porto    919-613-0469    angelo.porto@dm.duke.edu   
Contact: Naraida Balajonda    919-681-4377    narai.balajonda@duke.edu   
Principal Investigator: Edmund H Jooste, M.B, Ch.B.         
Sponsors and Collaborators
Duke University
Grifols Biologicals Inc.
Investigators
Principal Investigator: Edmund Jooste, MD Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02103114     History of Changes
Other Study ID Numbers: Pro00051186
Study First Received: April 1, 2014
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Antithrombin III Deficiency
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Blood Protein Disorders
Thrombophilia
Genetic Diseases, Inborn
Thrombin
Antithrombin III
Antithrombin Proteins
Antithrombins
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants

ClinicalTrials.gov processed this record on August 21, 2014