Efficacy of Amicar for Children Having Craniofacial Surgery

August 31, 2023 updated by: Children's National Research Institute

Efficacy of ε-Aminocaproic Acid (EACA) in Children Undergoing Craniofacial Reconstruction Surgery

The purpose of this study is to determine whether Amicar (ε-aminocaproic acid) is effective in reducing blood loss in children undergoing craniofacial reconstruction surgery.

The investigators hypothesize that Amicar will decrease intraoperative blood loss and decrease the need for perioperative blood product administration in children undergoing craniofacial surgery.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Craniosynostosis is a condition in which there is premature fusion of one or more of the sutures between the bones of the skull. Premature fusion of sutures in the skull limits the ability of the cranial vault to expand to accommodate the rapidly growing brain in infancy and early childhood and leads to bony deformation. Left uncorrected, craniosynostosis may adversely impact both neurologic and psychosocial development and in some cases, can result in high intracranial pressure and blindness.

Craniofacial (CF) reconstructive surgery is performed in young children with craniosynostosis to improve physical appearance, prevent functional neurologic disturbances, and enhance psychosocial development. Due to the complexities of the surgery as well as the young age and size of the patients, CF reconstruction carries potential life threatening risks and can result in significant morbidity. Reported complications include massive intraoperative hemorrhage, intraoperative cardiac arrest, transfusion-related reactions, venous air embolism, hypotension, coagulopathy, bradycardia, postoperative seizures, surgical site infections, facial swelling with airway compromise, and unplanned postoperative mechanical ventilation. The most severe and most common perioperative issues relate to the rate and extent of blood loss.

Fibrinolysis, which impairs adequate hemostasis, has been shown to occur in children during CF reconstruction. This most certainly contributes to the magnitude of blood loss in these types of operations. Thus, targeting this defect in clot hemostasis with the use of antifibrinolytics is a reasonable therapeutic approach.

Amicar (ε-aminocaproic acid) is a synthetic lysine analog that blocks the lysine binding sites on plasminogen, resulting in antifibrinolytic activity through inhibition of plasmin formation. We have chosen to study Amicar in this clinical context for a number of reasons. First, major hemorrhage continues to be a significant perioperative issue in this cohort. Secondly, Amicar is commonly and safely administered to children undergoing other types of high-risk surgery (i.e., spinal fusion surgery and open heart surgery). In addition, Amicar is inexpensive and easily administered, making it a viable and novel therapeutic option if shown to be effective for this type of surgery.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 3 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Any child diagnosed with craniosynostosis in need of surgical repair
  • Males and females between the ages of 2 - 36 months (minorities will be included)
  • Surgical procedure involving complex craniofacial reconstruction and craniotomy
  • Written informed consent from parent/guardian

Exclusion Criteria:

  • Subjects with known or suspected hypersensitivity reaction to Amicar or history of prior Amicar exposure
  • Presence or prior history of a known coagulation disorder or hypercoagulable state
  • Preoperative laboratory values that indicate clinically significant hematologic disease (hemoglobin, platelet count, prothrombin time, or partial thromboplastin time outside of normal range)
  • Subjects who are on anticoagulant therapy (Coumadin, heparin, aspirin, etc.)
  • Subjects with a prior history of a thrombotic event
  • History of renal malformation
  • Presence of hematuria
  • History of abnormal renal function - serum creatinine or blood urea nitrogen (BUN) value greater than 1.5 times the upper limit of the normal range
  • Craniofacial reconstruction surgery performed in conjunction with an additional surgical procedure associated with blood loss
  • Subjects who have been previously enrolled in this protocol may not be enrolled again

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Amicar (ε-aminocaproic acid)
Treatment group 1: Amicar 100 mg/kg (0.4 mL/kg) IV loading dose, followed by an intraoperative continuous infusion at 40 mg/kg/hr (0.16 mL/kg/hr) to be continued until skin closure.
Drug: Amicar (ε-aminocaproic acid)
Other Names:
  • Amicar
  • 6-aminohexanoic acid
  • epsilon aminocaproic acid
Placebo Comparator: normal saline
Treatment group 2: Equal volume of normal saline (placebo control) at the same rate as treatment group 1.
Drug: normal saline
Other Names:
  • placebo
  • placebo control
  • normal saline 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intraoperative blood loss
Time Frame: within the first 72 hours after surgery
As estimated blood loss is known to be inaccurate in this setting, mean intraoperative blood loss (in mL/kg) will be calculated using a formula previously described in this population.
within the first 72 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood donor exposure
Time Frame: within the first 30 days after surgery
To establish that intraoperative administration of Amicar decreases perioperative blood donor exposure and need for transfusion following craniofacial reconstructive surgery
within the first 30 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's National Research Institute

Investigators

  • Principal Investigator: Srijaya K Reddy, MD, MBA, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

August 28, 2014

First Submitted That Met QC Criteria

September 2, 2014

First Posted (Estimated)

September 3, 2014

Study Record Updates

Last Update Posted (Actual)

September 1, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO00004263

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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