Amicar Pharmacokinetics of Children Having Craniofacial Surgery

NCT00912119 | Completed Phase 1

• 1 other identifier: 08-007017
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Craniosynostosis

Keywords

craniofacial surgery; pharmacokinetics; cranial vault abnormalities; homologous blood products; wide scalp dissections; transfusion requirements

Outcome Measures

Primary Outcomes (1)

• pharmacokinetic parameters of EACA including clearance, AUC0-∞, half-life, and volume of distribution

  80 hours

Secondary Outcomes (4)

• Volume of homologous blood (mL/kg) transfused postoperatively

  72 hours

• Volume of homologous blood (mL/kg) transfused intraoperatively

  6 hours

• Safety and tolerability of EACA based on the occurrence of Adverse Events

  720 hours

• Potentially defining a Maximum Tolerated Dose (MTD) for EACA in the stated population

  6 hours

Study Arms (4)

Group A

EXPERIMENTAL

Group A - Low Dose

Drug: Epsilon-Aminocaproic Acid

Group B

EXPERIMENTAL

Group B - Intermediate Dose

Drug: Epsilon-Aminocaproic Acid

Group C

EXPERIMENTAL

Group C - High Dose

Drug: Epsilon-Aminocaproic Acid

Group D

EXPERIMENTAL

Group D - Extra Low

Drug: Epsilon-Aminocaproic Acid

Interventions

Epsilon-Aminocaproic Acid DRUG

Group C (high dose) will receive a loading dose of EACA of 100 mg/kg over ten minutes followed by a continuous EACA infusion at 40 mg/kg/hr, which will be continued until the end of surgery.

Also known as: Amicar, 6-aminohexanoic acid

Group C

Eligibility Criteria

• Age: 2 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males or females of every race and ethnicity ages 2 months- 24 months
• Diagnosis - Craniosynostosis (including syndromic craniosynostosis)
• Surgical procedure - Pediatric patients undergoing craniofacial reconstruction procedures involving a craniotomy
• Written informed parent/guardian consent

You may not qualify if:

• Children with known or suspected hypersensitivity reaction to epsilon-aminocaproic acid
• Subjects who do not have a parent or legal guardian who speaks English
• Presence of a known coagulation abnormality
• Presence of hematuria
• Presence of a preoperative coagulation test abnormality (PT or PTT outside of normal range)
• History of abnormal renal function
• Serum creatinine or blood urea nitrogen (BUN) value outside of normal range (collected within 30 days of proposed EACA administration)
• Initial intra-operative serum creatinine or BUN value outside of normal range
• Children undergoing strip craniectomy for sagittal craniosynostosis
• Presence of a preexisting neurologic deficit, seizure disorder, or other neurologic disorder
• History of congenital cardiac disease (does not include patent ductus arteriosis, patent foramen ovale, or spontaneously closed muscular ventricular septal defect)
• Children having other surgical procedures performed in addition to craniofacial reconstruction surgery
• Preoperative laboratory abnormalities that indicate clinically significant hematologic disease (collected within 30 days of proposed EACA administration):
• Hemoglobin \< 9 gm/dL Platelet count \< 100,000/mm3
• Any investigational drug use within 30 days prior to proposed EACA administration.

Sponsors & Collaborators

• Paul Stricker: lead
• Children's Anesthesiology Associates, Ltd.: collaborator
• Thomas B. and Jeannette E. Laws McCabe Fund Pilot Award: collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Craniosynostoses

Interventions

Aminocaproic Acid

Condition Hierarchy (Ancestors)

Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Aminocaproates; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Paul Stricker, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor for the University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia

Study Record Dates

• First Submitted: June 1, 2009
• First Posted: June 3, 2009
• Study Start: May 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: November 1, 2012

Record last verified: 2012-10

Locations

US (1)