CraniosynostosisPhase 2NCT02229968
Efficacy of Amicar for Children Having Craniofacial Surgery
A Phase 2 study testing Amicar (ε-aminocaproic acid) and normal saline in people with Craniosynostosis, run by Children's National Research Institute at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 2 to 36 months
- Conditions the study is for
- Craniosynostosis
- What is being tested?
- Amicar (ε-aminocaproic acid) and normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Mar 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: 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.
Read the 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.
- Conditions
- Craniosynostosis
- Being tested
- Amicar (ε-aminocaproic acid), normal saline
- Keywords
- craniosynostosis, craniofacial, amicar, epsilon aminocaproic acid, ε-aminocaproic acid
- Medical subject headings
- Craniosynostoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amicar (ε-aminocaproic acid)Drug
Also called Amicar, 6-aminohexanoic acid, epsilon aminocaproic acid
normal salineDrug
Also called normal saline 0.9%, placebo, placebo control
| Study group | Role | What they receive |
|---|---|---|
| Amicar (ε-aminocaproic acid) | Experimental | 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. Receives: Drug: Amicar (ε-aminocaproic acid) |
| normal saline | Placebo comparator | Treatment group 2: Equal volume of normal saline (placebo control) at the same rate as treatment group 1. Receives: Drug: normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intraoperative blood loss
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.
Measured: within the first 72 hours after surgery
Secondary outcomes (1)
Blood donor exposure
To establish that intraoperative administration of Amicar decreases perioperative blood donor exposure and need for transfusion following craniofacial reconstructive surgery
Measured: within the first 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2014 (estimated)
- Study startOct 2014
- Primary completionJan 2028 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for CraniosynostosisStudies of the same condition, open and under way.
- More trials run by Children's National Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's National Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Srijaya K Reddy, MD, MBA, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02229968
- Sponsor's protocol ID
- PRO00004263
- Status last verified
- Apr 2026
- First submitted
- 28 Aug 2014
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Stricker PA, Zuppa AF, Fiadjoe JE, Maxwell LG, Sussman EM, Pruitt EY, Goebel TK, Gastonguay MR, Taylor JA, Bartlett SP, Schreiner MS. Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery. Br J Anaesth. 2013 May;110(5):788-99. doi: 10.1093/bja/aes507. Epub 2013 Jan 25.
PubMed 23353035Faberowski LW, Black S, Mickle JP. Blood loss and transfusion practice in the perioperative management of craniosynostosis repair. J Neurosurg Anesthesiol. 1999 Jul;11(3):167-72. doi: 10.1097/00008506-199907000-00002.
PubMed 10414670Stricker PA, Shaw TL, Desouza DG, Hernandez SV, Bartlett SP, Friedman DF, Sesok-Pizzini DA, Jobes DR. Blood loss, replacement, and associated morbidity in infants and children undergoing craniofacial surgery. Paediatr Anaesth. 2010 Feb;20(2):150-9. doi: 10.1111/j.1460-9592.2009.03227.x.
PubMed 20078812Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, Ker K. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011 Mar 16;2011(3):CD001886. doi: 10.1002/14651858.CD001886.pub4.
PubMed 21412876Oppenheimer AJ, Ranganathan K, Levi B, Strahle JM, Kapurch J, Muraszko KM, Buchman SR. Minimizing transfusions in primary cranial vault remodeling: the role of aminocaproic acid. J Craniofac Surg. 2014 Jan;25(1):82-6. doi: 10.1097/SCS.0b013e3182a2e23f.
PubMed 24240766
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of ε-Aminocaproic Acid (EACA) in Children Undergoing Craniofacial Reconstruction Surgery
- ClinicalTrials.gov ID
- NCT02229968
- Acronym / sponsor ID
- PRO00004263
- Conditions
- Craniosynostosis
- Keywords
- craniosynostosis, craniofacial, amicar, epsilon aminocaproic acid, ε-aminocaproic acid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Children's National Research InstituteUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 3 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amicar (ε-aminocaproic acid) | Experimental | Drug: 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. |
| normal saline | Placebo comparator | Drug: normal salineTreatment group 2: Equal volume of normal saline (placebo control) at the same rate as treatment group 1. |
Who may qualify
- Ages
- 2 to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amicar (ε-aminocaproic acid)Also: Amicar, 6-aminohexanoic acid, epsilon aminocaproic acid | Drug | Amicar (ε-aminocaproic acid) |
| normal salineAlso: normal saline 0.9%, placebo, placebo control | Drug | normal saline |
Primary outcome
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.
1 secondary outcome
Blood donor exposure
Time frame: within the first 30 days after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Background: PubMed 23353035Stricker PA, Zuppa AF, Fiadjoe JE, Maxwell LG, Sussman EM, Pruitt EY, Goebel TK, Gastonguay MR, Taylor JA, Bartlett SP, Schreiner MS. Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery. Br J Anaesth. 2013 May;110(5):788-99. doi: 10.1093/bja/aes507. Epub 2013 Jan 25.
- Background: PubMed 10414670Faberowski LW, Black S, Mickle JP. Blood loss and transfusion practice in the perioperative management of craniosynostosis repair. J Neurosurg Anesthesiol. 1999 Jul;11(3):167-72. doi: 10.1097/00008506-199907000-00002.
- Background: PubMed 20078812Stricker PA, Shaw TL, Desouza DG, Hernandez SV, Bartlett SP, Friedman DF, Sesok-Pizzini DA, Jobes DR. Blood loss, replacement, and associated morbidity in infants and children undergoing craniofacial surgery. Paediatr Anaesth. 2010 Feb;20(2):150-9. doi: 10.1111/j.1460-9592.2009.03227.x.
- Background: PubMed 21412876Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, Ker K. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011 Mar 16;2011(3):CD001886. doi: 10.1002/14651858.CD001886.pub4.
- Background: PubMed 24240766Oppenheimer AJ, Ranganathan K, Levi B, Strahle JM, Kapurch J, Muraszko KM, Buchman SR. Minimizing transfusions in primary cranial vault remodeling: the role of aminocaproic acid. J Craniofac Surg. 2014 Jan;25(1):82-6. doi: 10.1097/SCS.0b013e3182a2e23f.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srijaya K Reddy, MD, MBA principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amicar (ε-aminocaproic acid) and normal saline in people with Craniosynostosis, run by Children's National Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intraoperative blood loss (time frame: within the first 72 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02229968, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.