Text Size

Antithrombin III Supplementation for Cardiopulmonary Bypass in Neonates

This study is currently recruiting participants.
Verified December 2012 by Medical College of Wisconsin
Sponsor:
Collaborators:
Children's Research Institute
GTC Biotherapeutics
Information provided by (Responsible Party):
Robert Niebler, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01158729
First received: June 17, 2010
Last updated: December 31, 2012
Last verified: December 2012
History of Changes
  Purpose

A prospective, randomized, placebo-controlled, double-blinded pilot study is planned. Neonates undergoing surgeries requiring cardiopulmonary bypass will receive antithrombin III (ATIII) supplementation or placebo in addition to standard anticoagulation with heparin as currently practiced at Children's Hospital of Wisconsin. We plan to enroll the first 60 sequential patients meeting criteria who consent to inclusion. The primary outcomes will be rates of adverse events to monitor safety. Secondary outcomes include volume of postoperative blood loss and packed red blood cell transfusion during the first 24 postoperative hours, and ATIII levels during and after bypass to determine pharmacokinetics.


Condition Intervention Phase
Postoperative Hemorrhage
 Drug: Antithrombin (Recombinant)
Other: Placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
Official Title: Antithrombin III Supplementation Prior to Cardiopulmonary Bypass for Neonates

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Measurements of safety will be same or less than placebo controls. [ Time Frame: Hospital Discharge ] [ Designated as safety issue: Yes ]
    Mortality rate, incidence of ECMO support within 24 hours postoperatively, incidence of mediastinal exploration within 24 hours postoperatively, incidence of thrombotic disease at discharge (ultrasound or other radiographic evidence if obtained for routine patient care), incidence of intracranial hemorrhage (ultrasound or computed tomography if obtained for routine patient care), days to delayed sternal closure, days to cessation of mechanical ventilation, and days to hospital discharge in the experimental and control groups.


Secondary Outcome Measures:
  • Postoperative blood loss [ Time Frame: 24 hours postoperatively ] [ Designated as safety issue: Yes ]
    Blood loss will be volumes (mL/kg) of blood loss and chest tube output from 10 minutes after protamine administration to 24 hours after ICU admission. We will compare this data to placebo controls.

  • Postoperative pRBC transfusion volume [ Time Frame: 24 hours postoperatively ] [ Designated as safety issue: Yes ]
    Transfusion will be volumes (mL/kg) of pRBC transfuion and 0.5 times volumes (mL/kg) of whole blood transfusion from 10 minutes after protamine administration to 24 hours after ICU admission. We will compare this data to placebo controls.

  • ATIII pharmacokinetics [ Time Frame: 24 hours postoperatively ] [ Designated as safety issue: Yes ]
    ATIII levels drawn preoperatively, within 30 minutes after administration (prior to start of CPB), within 30 minutes of start of CPB, just prior to discontinuation of CPB, and upon admission to the ICU will be assessed to determine if the single dose of ATIII sustained normal ATIII levels in the experimental group throughout these time periods.


Estimated Enrollment: 60
Study Start Date: August 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATIII experimental group
30 neonates (4-30 days of age) undergoing surgery requiring cardiopulmonary bypass will receive Antithrombin (Recombinant) prior to initiation of bypass
 Drug: Antithrombin (Recombinant)
Single dose of antithrombin (recombinant) to be given prior to initiation of cardiopulmonary bypass. Intravenous dose determined by following formula: ATIII dose given to patient = [(1.0 Units/mL - patient's measured ATIII concentration in Units/mL) X weight (kg) X 80 mL/kg] X (1 mL/175 Units)
Other Names:
  • ATryn
  • Recombinant antithrombin
Placebo Comparator: Placebo Controls
30 neonates (4-30 days of age) undergoing surgery requiring cardiopulmonary bypass will receive placebo prior to initiation of bypass
 Other: Placebo
Single dose of placebo (0.9% NaCl) to be given prior to initiation of cardiopulmonary bypass. Intravenous dose determined by following formula: Placebo dose given to patient = [(1.0 Units/mL - patient's measured ATIII concentration in Units/mL) X weight (kg) X 80 mL/kg] X (1 mL/175 Units)
Other Names:
  • 0.9% NaCl
  • Normal Saline

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

all sequential neonates (4 - 30 days of age) undergoing surgery requiring cardiopulmonary bypass are eligible to be included in the study.

Exclusion Criteria:

  • prior operation utilizing cardiopulmonary bypass
  • weight less than 2 kilograms
  • prematurity less than 37 weeks estimated gestational age
  • previously diagnosed pro-thrombotic or hemorrhagic disorder
  • known intracranial hemorrhage
  • prior ATIII supplementation
  • prior therapeutic anticoagulant use
  • known hypersensitivity to goat and goat milk proteins.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01158729

Contacts
Contact: Robert A Niebler, M.D. 414-266-3360 rniebler@mcw.edu

Locations
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Robert A Niebler, M.D.     414-266-3360     rniebler@mcw.edu    
Principal Investigator: Robert A Niebler, M.D.            
Sponsors and Collaborators
Medical College of Wisconsin
Children's Research Institute
GTC Biotherapeutics
Investigators
Principal Investigator: Robert A Niebler, M.D. Medical College of Wisconsin
  More Information

Publications:

Responsible Party: Robert Niebler, Assistant Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01158729     History of Changes
Other Study ID Numbers: Ped-ATIII CPB 001
Study First Received: June 17, 2010
Last Updated: December 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Medical College of Wisconsin:
Antithrombin III
Postoperative Hemorrhage
Cardiopulmonary Bypass
Pediatrics
Blood Transfusion

Additional relevant MeSH terms:
Hemorrhage
Postoperative Hemorrhage
Pathologic Processes
Postoperative Complications
Antithrombins
Antithrombin III
Antithrombin Proteins
Serine Proteinase Inhibitors
 Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013