Antithrombin III Supplementation for Cardiopulmonary Bypass in Neonates

NCT01158729 | Terminated Phase 1 DMC

• 1 other identifier: Ped-ATIII CPB 001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Hemorrhage

Keywords

Antithrombin III; Postoperative Hemorrhage; Cardiopulmonary Bypass; Pediatrics; Blood Transfusion

Outcome Measures

Primary Outcomes (1)

• Measurements of safety will be same or less than placebo controls.

  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.

  Hospital Discharge

Secondary Outcomes (3)

• Postoperative blood loss

  24 hours postoperatively

• Postoperative pRBC transfusion volume

  24 hours postoperatively

• ATIII pharmacokinetics

  24 hours postoperatively

Study Arms (2)

ATIII experimental group

EXPERIMENTAL

30 neonates (4-30 days of age) undergoing surgery requiring cardiopulmonary bypass will receive Antithrombin (Recombinant) prior to initiation of bypass

Drug: Antithrombin (Recombinant)

Placebo Controls

PLACEBO COMPARATOR

30 neonates (4-30 days of age) undergoing surgery requiring cardiopulmonary bypass will receive placebo prior to initiation of bypass

Other: Placebo

Interventions

Antithrombin (Recombinant) DRUG

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)

Also known as: ATryn, Recombinant antithrombin

ATIII experimental group

Placebo OTHER

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)

Also known as: 0.9% NaCl, Normal Saline

Placebo Controls

Eligibility Criteria

• Age: 4 Days - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Children's National Research Institute: collaborator
• rEVO Biologics: collaborator

Study Sites (1)

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (21)

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MeSH Terms

Conditions

Postoperative Hemorrhage

Interventions

Antithrombins; Saline Solution

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications

Intervention Hierarchy (Ancestors)

Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticoagulants; Hematologic Agents; Therapeutic Uses; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Robert A Niebler, M.D.

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: July 8, 2010
• Study Start: August 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 20, 2014

Record last verified: 2014-01

Locations

US (1)