Clinical Trial: Antithrombin III Supplementation for Cardiopulmonary Bypass in Neonates

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Antithrombin III Supplementation Prior to Cardiopulmonary Bypass for Neonates

Brief Summary: 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.

Detailed Summary:

Hypothesis:

ATIII supplementation prior to initiation of cardiopulmonary bypass (CPB) to neonates will be safe and result in less postoperative bleeding and transfusion of packed red blood cells (pRBC) as compared to placebo controls.

Specific Aims:

  1. To determine the safety and feasibility of ATIII supplementation prior to initiation of CPB in neonates.
  2. To determine the pharmacokinetics of ATIII supplementation prior to initiation of CPB in neonates
  3. To compare the postoperative blood loss and pRBC transfusion requirements in an experimental group of neonates undergoing surgery requiring CPB who receive ATIII prior to initiation of CPB to that of a placebo control group that did not receive ATIII.

Inclusion Criteria:

All sequential neonates (4-30 days of age) undergoing surgeries that require CPB at CHW are eligible to be included in the study.

Exclusion Criteria:

Patients with a prior operation utilizing CPB, 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, and prior therapeutic anticoagulant use.

Protocol:

After informed consent, patients will be risk stratified into two groups based on whether the planned surgery will result in a cyanotic or acyanotic palliation. The patients in these two groups will then be random
Sponsor: Medical College of Wisconsin

Current Primary Outcome: Measurements of safety will be same or less than placebo controls. [ Time Frame: Hospital Discharge ]

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.


Original Primary Outcome: Measurements of safety will be same or less than historical controls over the last two years from CHW. [ Time Frame: Hospital Discharge ]

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.


Current Secondary Outcome:

  • Postoperative blood loss [ Time Frame: 24 hours postoperatively ]
    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 ]
    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 ]
    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.


Original Secondary Outcome:

  • Postoperative blood loss [ Time Frame: 24 hours postoperatively ]
    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 historical controls.
  • Postoperative pRBC transfusion volume [ Time Frame: 24 hours postoperatively ]
    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 historical controls.
  • ATIII pharmacokinetics [ Time Frame: 24 hours postoperatively ]
    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.


Information By: Medical College of Wisconsin

Dates:
Date Received: June 17, 2010
Date Started: August 2011
Date Completion:
Last Updated: January 16, 2014
Last Verified: January 2014