Clinical Trial: Amicar Pharmacokinetics of Children Having Craniofacial Surgery

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pharmacokinetics of Epsilon-Aminocaproic Acid in Children Undergoing Craniofacial Reconstruction Surgery

Brief Summary:

Craniofacial reconstruction surgery involves a surgical approach to the craniofacial region to repair cranial vault and facial deformities. The surgery is extensive, often requiring wide scalp dissections and multiple osteotomies and has been associated with significant morbidity. Some of the most severe and commonly seen problems are associated with the rate and extent of blood loss.

Efforts to minimize surgical bleeding may translate to reduced transfusion requirements and a lessening of associated risks Epsilon-aminocaproic acid (EACA), an inhibitor of fibrinolysis, reduces transfusion requirements in children undergoing procedures on cardiopulmonary bypass (CPB), as well as in older children undergoing spinal surgery for scoliosis (1-6).

Before controlled studies to assess efficacy of EACA in a craniofacial surgical population can be done, appropriate pharmacokinetic (PK) data are needed to determine the optimal dosing strategy. PK data exist for EACA in children undergoing operations on CPB and hypothermia.

The aim of this study is to determine the pharmacokinetics of EACA in infants and children undergoing craniofacial reconstruction procedures.


Detailed Summary:

Craniosynostosis is the condition in which there is premature fusion of one or more of these sutures between the bones of the skull. Craniosynostosis limits the ability of the cranial vault to expand to accommodate the rapidly growing brain in infancy and early childhood. Deformation of skull shape results as cranial vault expansion occurs in areas of the skull that have not abnormally fused. Left uncorrected, craniosynostosis may adversely impact neurologic and psychosocial development. In some cases, increased intracranial pressure may also result.

Craniofacial (CF) reconstruction procedures to treat craniosynostosis are undertaken in young children to improve appearance, prevent functional disturbances, and enhance psychosocial development. Optimal surgical results are achieved when these procedures are performed in infancy. These procedures are extensive, often requiring wide scalp dissections and multiple osteotomies and have been associated with significant morbidity. Reported complications include massive blood loss, intraoperative cardiac arrest, transfusion reactions, venous air embolism, hypotension, coagulopathy, bradycardia, postoperative seizures, surgical site infections, facial swelling, and unplanned postoperative mechanical ventilation (7-13). Many of the most severe and commonly seen problems are associated with the rate and extent of blood loss.

Intraoperatively, the presence of hyperfibrinolysis has been demonstrated in children undergoing CF reconstruction procedures (8,14), although the extent of its contribution to bleeding is unclear.

Epsilon-aminocaproic acid (EACA), another inhibitor of fibrinolysis, is an attractive alternative. EACA is a synthetic lysine analog that blocks the lysine binding sites on plasminogen, resulting in antifibrinolytic act
Sponsor: Paul Stricker

Current Primary Outcome: pharmacokinetic parameters of EACA including clearance, AUC0-∞, half-life, and volume of distribution [ Time Frame: 80 hours ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Volume of homologous blood (mL/kg) transfused postoperatively [ Time Frame: 72 hours ]
  • Volume of homologous blood (mL/kg) transfused intraoperatively [ Time Frame: 6 hours ]
  • Safety and tolerability of EACA based on the occurrence of Adverse Events [ Time Frame: 720 hours ]
  • Potentially defining a Maximum Tolerated Dose (MTD) for EACA in the stated population [ Time Frame: 6 hours ]


Original Secondary Outcome: Same as current

Information By: Children's Hospital of Philadelphia

Dates:
Date Received: June 1, 2009
Date Started: May 2009
Date Completion:
Last Updated: October 31, 2012
Last Verified: October 2012