Adolescent idiopathic scoliosis surgery is an extensive procedure associated with
significant blood loss frequently requiring the transfusion of blood. Tranexamic acid (TXA)
is a synthetic antifibrinolytic (prevents breakdown of the blood clot) that has been used to
extensively reduce transfusion in pediatric major surgery, including cardiac, craniofacial
and orthopedic surgery. In this prospective randomized double-blinded study, the
investigators wish to evaluate the hypothesis that TXA is more effective than standard of
care at decreasing blood loss and blood transfusion perioperatively in children and
adolescents undergoing idiopathic scoliosis surgery.
This prospective randomized double-blinded study will enroll 120 children and adolescents
ages undergoing scoliosis repair with the diagnosis of idiopathic scoliosis. The primary aim
is to determine if intravenous infusion of TXA is more effective than standard care (no TXA)
at decreasing blood loss and blood transfusion perioperatively in children and adolescents
presenting for scoliosis surgery.
1. Investigate and compare the efficacy of TXA (as measured by intraoperative blood loss
and blood transfusion) intravenously administered during surgery vs placebo in patients
with idiopathic scoliosis coming for surgery.
2. Determine the PK profile of TXA in children and adolescents undergoing scoliosis
3. Investigate the contribution of these different factors (plasma concentration of TXA,
age related differences in PK/PD and renal function, and polymorphism of the
Plasminogen activator inhibitor-1 (PAI-1) gene and PAI-1 levels with TXA efficacy in
pediatric patients undergoing and scoliosis surgery.
4. Determine the safety profile of intravenous TXA in children and adolescents presenting
for scoliosis surgery.
Following a standardized general anesthetic protocol, patients coming with idiopathic
scoliosis will be randomized to either:
1. placebo i.e. saline 0.9% (intravenous injection)
2. intravenous TXA given as a loading dose over 15 minutes of 50 mg/kg bolus ( 30- 60
minutes prior to surgical incision) and 10 mg/kg/hr infusion for the duration of the
During the surgery, we will follow standardized, defined fluid, blood and blood production
The following data are part of routine patient care and will be collected for study
1. Age, weight, height, gender, race, coexisting diseases, preoperative hemoglobin,
hematocrit, platelets, PT, PTT, and INR, creatinine.
2. Intraoperative data: total volume of intraoperative blood loss as estimated by weighing
sponges amount of blood in suction canisters, total volumes and units of blood products
administered, total volume of cell saver blood administered, total volumes of
crystalloid and colloid agents administered, hemodynamic parameters; mean arterial
blood pressure & heart rate, total urine output, total surgical time, and number spinal
3. Laboratory data: Perioperative baseline and serial hemoglobin, hematocrit, platelet
count, PT, PTT, INR and fibrinogen as dictated by standard clinical practice.
4. Postoperative data collection will include: blood transfusion requirement in the first
24 hours after surgery, amount of blood collected in the surgical drains for the first
24 hours postoperatively, the occurrence of any postoperative complications and
duration of ICU and hospital stay.
A research team member will follow the patient daily after the surgery and a follow-up phone
call will be made to the family at one month after discharge from the hospital with the aim
to identify adverse events related to TXA. Potential adverse advents include
hypersensitivity or allergic reaction to tranexamic acid, thromboembolic events,
neurological complications, and development of renal insufficiency. Adverse events will be
reported immediately to the IRB as per institutional protocols. As the estimate of blood
loss is somewhat inaccurate, blood loss will also be calculated as previously described.
The following measures are not part of routine patient care but are required by the study
During the course of the operation, a total of four samples consisting of 2 ml each of blood
will be drawn from the arterial catheter for DNA, PAI-1 protein level, and baseline TXA.
After the study drug infusion is started, subsequent 2 ml samples will be drawn utilizing
one of four different sampling schemes randomly assigned.
TXA plasma concentrations will be measured as described with some modifications we have made
in our laboratory18. The samples will be immediately anticoagulated with ethylene diamine
tetraacetic acid (EDTA) and stored on ice. Plasma will be separated by centrifugation (1000g
x10 min at 4oC) and stored at -70 oC pending analysis for TXA concentrations. TXA plasma
concentrations will be measured using high performance liquid chromatography (HPLC) after
ultrafiltration and derivatization18.
Potential eligibility for the study will be identified via the surgical schedule which will
be screened daily by a designated member of the research team. A cover letter, brochure, and
consent form will be mailed to the prospective patient's family prior to the scheduled
pre-operative appointment. The study protocol will be reviewed with the patient/family and
all queries will be addressed on the day of the visit to the preoperative clinic prior to
the scheduled date of surgery. Informed consent will be obtained from the parents/legal
guardians as per institutional IRB guidelines. The child's assent (when appropriate) will
also be obtained at least 24 hours before the scheduled surgery when possible.
Data Analysis Plan:
A preliminary power analysis indicated that a total sample size of 120 children randomized
equally to TXA vs. standard of care (no TXA) will provide 80% power (α = 0.05, β = 0.20) to
detect a decrease from 30% to 10% of patients loosing a significant amount of blood (defined
as >/= 25 ml/kg) using a chi-square test of independent binomial proportions assuming a
standard deviation of 25% (effect size = 1.2) (version 7.0, nQuery Advisor, Statistical
Solutions, Saugus, MA).
Adverse Event Criteria and Reporting Procedures:
Potential adverse events include hypersensitivity or allergic reaction to tranexamic acid or
any component, thromboembolic events, neurologic events such as seizures, hypotension (with
rapid IV administration). In awake patients, the following has been reported: nausea,
diarrhea or vomiting. The patients will be assessed the next day by a member of the research
team and interviewed for the occurrence of any of these adverse events. In the event of a
serious adverse event, it will be reported to the IRB immediately and the study halted until
a thorough investigation into the cause can be made.
Data and Safety Monitoring Plan Data collection for this study will include the collection
of any data pertaining to adverse events. Any adverse events will be promptly reported to
the IRB and the members of the research team responsible for data and safety monitoring.
Data and safety monitoring will be reviewed by the research team every 10 subjects recruited
or earlier if a specific problem is identified
- Children and adolescents (age 10-21 yr) for elective Idiopathic scoliosis corrective
surgery; posterior repair.
- Preexisting coagulopathy, (INR>1.4, PTT>1.4xN, PT>1.4xN, platelet count<150,000/mm3),
severe hematological disorders, hepatic failure, or renal failure. Ingestion of
acetylsalicylate within 14 days or NSAIDs within 2 days of the scheduled surgery
date; history of prior blood transfusion. Pre-donation of autologous blood. Patients
having anterior-posterior repair.