CraniosynostosisPhase 1NCT00912119
Amicar Pharmacokinetics of Children Having Craniofacial Surgery
A Phase 1 study testing Epsilon-Aminocaproic Acid in people with Craniosynostosis, run by Paul Stricker at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 24 months
- Conditions the study is for
- Craniosynostosis
- What is being tested?
- Epsilon-Aminocaproic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Oct 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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)
- Known history of a coagulation disorder in either parent. Children in whom this history is not available (e.g., adopted children) will be eligible for study inclusion.
Show all 18Show fewer
- 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.
- Wards are not eligible for study
- Children who have been previously enrolled in this study may not be enrolled again.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pharmacokinetics of Epsilon-Aminocaproic Acid in Children Undergoing Craniofacial Reconstruction Surgery
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).
Read more
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.
Read the detailed description
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 activity through inhibition of plasmin formation.
We have chosen to study EACA in this population.
- Conditions
- Craniosynostosis
- Being tested
- Epsilon-Aminocaproic Acid
- Keywords
- craniofacial surgery, pharmacokinetics, cranial vault abnormalities, homologous blood products, wide scalp dissections, transfusion requirements
- Medical subject headings
- Craniosynostoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epsilon-Aminocaproic AcidDrug
Also called Amicar, 6-aminohexanoic acid
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.
Epsilon-Aminocaproic AcidDrug
Also called Amicar, 6-aminohexanoic acid
Group A (low dose) will receive a loading dose of EACA of 25 mg/kg over ten minutes followed by a continuous EACA infusion at 10 mg/kg/hr, which will be continued until the end of surgery
Epsilon-Aminocaproic AcidDrug
Also called Amicar, 6-aminohexanoic acid
Group B (intermediate dose) will receive a loading dose of EACA of 50 mg/kg over ten minutes followed by a continuous EACA infusion at 20 mg/kg/hr, which will be continued until the end of surgery
Epsilon-Aminocaproic AcidDrug
Also called Amicar, 6-aminohexanoic acid
Group D (extra low dose) will receive a loading dose of EACA of 12.5 mg/kg over ten minutes followed by a continuous EACA infusion at 5 mg/kg/hr, which will be continued until the end of surgery
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Group A - Low Dose Receives: Drug: Epsilon-Aminocaproic Acid |
| Group B | Experimental | Group B - Intermediate Dose Receives: Drug: Epsilon-Aminocaproic Acid |
| Group C | Experimental | Group C - High Dose Receives: Drug: Epsilon-Aminocaproic Acid |
| Group D | Experimental | Group D - Extra Low Receives: Drug: Epsilon-Aminocaproic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetic parameters of EACA including clearance, AUC0-∞, half-life, and volume of distribution
Measured: 80 hours
Secondary outcomes (4)
Volume of homologous blood (mL/kg) transfused postoperatively
Measured: 72 hours
Volume of homologous blood (mL/kg) transfused intraoperatively
Measured: 6 hours
Safety and tolerability of EACA based on the occurrence of Adverse Events
Measured: 720 hours
Potentially defining a Maximum Tolerated Dose (MTD) for EACA in the stated population
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2009 (estimated)
- Study startMay 2009
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CraniosynostosisStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paul Stricker
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Anesthesiology Associates, Ltd., Thomas B. and Jeannette E. Laws McCabe Fund Pilot Award
- Responsible party
- Sponsor-investigator, Paul Stricker, Children's Hospital of Philadelphia
- Investigators
- Paul Stricker, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00912119
- Sponsor's protocol ID
- 08-007017
- Status last verified
- Oct 2012
- First submitted
- 1 Jun 2009
- Last updated
- 1 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Epsilon-Aminocaproic Acid in Children Undergoing Craniofacial Reconstruction Surgery
- ClinicalTrials.gov ID
- NCT00912119
- Acronym / sponsor ID
- 08-007017
- Conditions
- Craniosynostosis
- Keywords
- craniofacial surgery, pharmacokinetics, cranial vault abnormalities, homologous blood products, wide scalp dissections, transfusion requirements
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Paul StrickerUniversity, hospital or other
- Collaborators
- Children's Anesthesiology Associates, Ltd., Thomas B. and Jeannette E. Laws McCabe Fund Pilot Award
- Study start
- May 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 3 Jun 2009 (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.
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 description
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 activity through inhibition of plasmin formation.
We have chosen to study EACA in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Epsilon-Aminocaproic AcidGroup A - Low Dose |
| Group B | Experimental | Drug: Epsilon-Aminocaproic AcidGroup B - Intermediate Dose |
| Group C | Experimental | Drug: Epsilon-Aminocaproic AcidGroup C - High Dose |
| Group D | Experimental | Drug: Epsilon-Aminocaproic AcidGroup D - Extra Low |
Who may qualify
- Ages
- 2 to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
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 |
|---|---|---|
| Epsilon-Aminocaproic AcidAlso: Amicar, 6-aminohexanoic acidGroup 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. | Drug | Group C |
| Epsilon-Aminocaproic AcidAlso: Amicar, 6-aminohexanoic acidGroup A (low dose) will receive a loading dose of EACA of 25 mg/kg over ten minutes followed by a continuous EACA infusion at 10 mg/kg/hr, which will be continued until the end of surgery | Drug | Group A |
| Epsilon-Aminocaproic AcidAlso: Amicar, 6-aminohexanoic acidGroup B (intermediate dose) will receive a loading dose of EACA of 50 mg/kg over ten minutes followed by a continuous EACA infusion at 20 mg/kg/hr, which will be continued until the end of surgery | Drug | Group B |
| Epsilon-Aminocaproic AcidAlso: Amicar, 6-aminohexanoic acidGroup D (extra low dose) will receive a loading dose of EACA of 12.5 mg/kg over ten minutes followed by a continuous EACA infusion at 5 mg/kg/hr, which will be continued until the end of surgery | Drug | Group D |
Primary outcome
pharmacokinetic parameters of EACA including clearance, AUC0-∞, half-life, and volume of distribution
Time frame: 80 hours
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2012.
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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.
Paul Stricker, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Epsilon-Aminocaproic Acid in people with Craniosynostosis, run by Paul Stricker 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 18 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: finished, as of the sponsor's last update on 1 Nov 2012. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
pharmacokinetic parameters of EACA including clearance, AUC0-∞, half-life, and volume of distribution (time frame: 80 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Nov 2012.