Tranexamic Acid (TXA) Versus Epsilon Aminocaproic Acid (EACA) Versus Placebo for Spine Surgery
Information source: New York University
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Scoliosis
Intervention: Tranexamic Acid (Drug); Normal Saline (Drug); Epsilon aminocaproic acid (Drug)
Phase: Phase 4
Sponsored by: New York University
Official(s) and/or principal investigator(s):
Thomas J Errico, MD, Principal Investigator, Affiliation: New York University School of Medicine - Department of Orthopaedic Surgery
Baron S Lonner, MD, Principal Investigator, Affiliation: New York University - Department of Orthopaedic Surgery
Thomas J Errico, MD, Phone: (212)263-7182, Email: firstname.lastname@example.org
Tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been reported to reduce
blood loss in the cardiac surgery literature but they have not been reported in use
head-to-head in the orthopedic surgery literature. In a randomized, double-blind,
prospective study we believe that TXA will be more effective than both EACA and placebo at
reducing blood loss for corrective spinal surgery.
Official title: A Prospective, Randomized, Double-blinded Single-site Control Study Comparing Blood Loss Prevention of Tranexamic Acid (TXA) to Epsilon Aminocaproic Acid (EACA) for Corrective Spinal Surgery
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Total Blood Loss over Course of Stay (Intraoperative and Postoperatively until discharge)
Total Units of Autologous and allogenic transfusion (Both intraoperatively and postoperatively until discharge)
Length of Hospital Stay from admission until Patient Discharge
Study Design The study is designed as a prospective, randomized, double-blinded control
trial. The patient, researcher, surgeon, and anesthesiologist will all be blinded to the
patient's treatment. Patients will either receive TXA, EACA, or normal saline. The study
will determine and compare differences in blood loss intra-operatively and estimate blood
loss postoperatively through monitoring of subfascial Hemovac drain outputs at the incision
site between the three groups. Postoperatively, laboratory values, drain outputs, and
clinical outcomes will be carefully followed.
The primary goal of this study is to compare the efficacy of TXA to EACA to placebo in
patients undergoing corrective spinal surgery for adolescent idiopathic scoliosis (AIS),
neuromuscular scoliosis (NMS), and with adult deformity (AD). Outcome measures will include
intra-operative and perioperative blood loss, transfusion rates, complete blood counts, and
coagulation profiles, as well as postoperative wound drainage, complications, and length of
Standardized treatment protocol For EACA, the loading dose is 100mg/kg infused over 15
minutes, while the maintenance dose is 10mg/kg hr. For TXA, the loading dose is 10mg/kg
infused over 15 minutes, while the maintenance dose is 1/mg/kg hr. Since TXA is prepared by
pharmacy at a concentration ten times less than the concentration of EACA, the volume of
medication administered during the loading and maintenance phase is identical. This is the
ideal method for physician blinding and has been discussed in depth with the anesthesia
department. The dosing regimen is also in accordance with existing guidelines and current
literature. The literature also reports safely using TXA at a 100mg/kg loading dose
followed by a 10mg/kg hr maintenance dose. However, improved efficacy at this higher dose
of TXA has not been proven in a single orthopedic study. Since TXA is reported to be ten
times more potent than EACA, delivering a dose of TXA that is ten times smaller than EACA is
valid and well supported in the literature.
Surgical correction of the spine Dorsal lumbar access is achieved by a posterior lumbar skin
incision along the midline. Paravertebral muscles are dissected away from bony structures
taking care to achieve adequate hemostasis. Multi-level spinal osteotomies and/or releases
of bony and ligamentous structures are performed to increase mobility of the spinal column.
Bone grafts consisting of autologous bone or allograft are filled in to allow for bony
fusion of the spinal column and limit motion. Pedicle screws are placed segmentally into
vertebral bodies to provide adequate fixation of rod instrumentation. Stainless steel,
titanium, or cobalt rods are placed to help correct and stabilize the spine while fusion
occurs. Generally the greatest blood loss occurs during dissection and placement of pedicle
screws while rod placement is associated with less blood loss. Subfascial Hemovac or
Jackson-Pratt drains are placed at the wound site during closure to allow for adequate
drainage and determination of post-operative blood loss.
Investigation schedule and follow-up Data will be collected pre-operatively regarding
individual patient demographics, laboratory values, and the surgical procedure to be
performed. Intra-operatively, data will be gathered to estimate blood loss and account for
changes in fluid balance. Anesthesiologists are asked to maintain a MAP of 60 during the
surgical exposure and anchor placement and a MAP of 70-90 during the surgical correction.
Similarly, surgeons are asked to place only subfascial Hemovac drains at the incision site.
These are both standard practice and have . Postoperatively, laboratory values, drain
output, and clinical outcomes are carefully followed until the patient is discharged. Given
the increased risk of renal failure with the use of Aprotinin changes in BUN to CR ratio are
carefully monitored post-operatively. This data is recorded onto a de-identified data
collection sheet by the researchers. These patient data sheets are then entered onto a
protected electronic database, while the data sheets are stored as a back-up until the study
is complete. Once the completed database is analyzed and summarized, the results will be
presented to the involved participants without any identifiable patient information.
Statistical considerations While useful, this analysis is limited by the great variability
in study design and control groups between prior orthopedic studies. Since no orthopedic
study has compared TXA and EACA together, conducting a power analysis required pooling of
data from two or three studies. This proved difficult, as control groups were dissimilar
between the studies.
Power analysis was performed multiple times using data from several studies. When
estimating the sample size required comparing TXA and EACA, attempts were made to choose two
studies with similar intra-operative blood losses within the control groups. A cardiac
study, albeit with dissimilar sample variance, was also used to estimate the sample size
needed for this study. Finally, determining the sample size for outcomes of total blood
loss and transfusion requirements proved difficult as even fewer studies reported these
outcomes. Blood loss will be estimated in the operation room, but will also be calculated
taking into account patient body mass, pre/postoperative hematocrit, and relative fluid
balance. This will minimize the variance in reported blood loss. A power analysis will be
performed again once 60 patients with AIS, NMS, or AD have been enrolled into the study.
With a single institution of surgeons and anesthesiologists participating in the study, we
expect a smaller variation in operative blood loss than reported in prior studies. Data
will not only be analyzed for all patients collectively, but will also be stratified by
diagnosis (AIS, NMS, and AD). The purpose of stratifying into these groups is threefold.
First, separation by diagnosis allows for more diligent control of patient-related factors
that may affect blood loss and transfusion rate. Secondarily, stratification by diagnosis
allows for a better understanding of which patients benefit most from one treatment option
over another. Lastly, it allows for a broader application of the results from this study
not only to patients with AIS, but to all spinal deformity patients.
An analysis of variance, univariate, and multivariate logistic regression analysis will be
used to analyze the difference in outcomes. Odds ratios will be calculated regarding the
risk for autologous or allogenic transfusion both intra and postoperatively. P-values will
be calculated regarding the relative blood loss in the intra and postoperative periods as
well. The groups will be analyzed to characterize the homogeneity of their pre-operative
characteristics that may influence blood loss. Patients with AIS, NMS or AD will be
stratified by primary diagnosis and analyzed separately but also collectively accounting for
patient and surgery-related confounders. Non-continuous data will be analyzed with a
non-parametric test. Pre-operative curve characteristics including Cobb angle and number of
vertebrae fused will be categorized to ensure similar groups for comparison.
Minimum age: 10 Years.
Maximum age: 80 Years.
- Undergoing thoracic and/or lumbar surgery for correction of adolescent idiopathic
scoliosis, neuromuscular scoliosis, or adult deformity for correction of condition
via posterior spinal fusion of 6 levels or greater.
- No renal dysfunction identified by elevated blood urea nitrogen (BUN) and creatinine
(CR) or BUN to CR ratio greater than 20: 1
- Hold religious and/or other beliefs limiting blood transfusion
- Currently use anti-coagulant medication or have past medical history leading to
abnormal coagulation profile pre-operatively
- Significant past medical history preventing the use of TXA or EACA described in the
Locations and Contacts
Thomas J Errico, MD, Phone: (212)263-7182, Email: email@example.com
New York University School of Medicine - Department of Orthopaedic Surgery - Spine, New York, New York 10016, United States; Recruiting
Thomas J Errico, MD, Principal Investigator
Baron S Lonner, MD, Principal Investigator
Kushagra Verma, MS, Sub-Investigator
Starting date: December 2008
Last updated: August 12, 2009