Spinal Fusion
Conditions
Brief summary
The purpose of this study is to see if Tranexamic Acid can safely reduce bleeding in people undergoing spinal fusion surgery.
Detailed description
This will be a multicenter, randomized, double-blind, parallel group study comparing tranexamic acid (test) to placebo (control) for reduction of perioperative blood loss after complex spinal fusion surgery (defined as T2 to Pelvis/Sacrum and greater than 4 Functional Spinal Units (4 discs/motion segments=5 Vertebral segments)). In addition to test and control treatments, all patients undergoing spinal fusion surgery will receive anesthesia and standard of care for blood loss including colloid/crystalloid fluid replacement and packed red cells, if necessary, according to a common multi-institutional protocol. Anesthesia will keep the mean arterial pressure as low as safe for the patient during exposure of surgery (estimated at 60-80 MAP). Patients will be randomized to receive either 30 mg/kg tranexamic acid as a one hour infusion (3 mL/kg) loading dose prior to start of procedure and as an infusion at 3 mg/kg/h (0.3 mL/kg/h) of tranexamic acid throughout the surgery in the test group; or, a one hour infusion at 3 mL/kg of 0.9% saline prior to start of the procedure and an infusion of 0.9% saline at 0.3 mL/kg/h in the control group. The maximum total dose will be 50 mg/kg. The active phase of the study will be until discharge postoperatively for efficacy measurements and at 6 weeks for safety follow-up. The randomization will be open only to the statistician generating the randomization sequence. All PI(s), study conduct and monitoring staff, as well as the subjects will be completely blinded to the treatments except in the case of emergency. The study will be terminated if ≥5/12 or 10/36 patients enrolled in the study are diagnosed with treatment related serious adverse events.
Interventions
Inactive ingredient mixture for injection without drug, intravenous infusion bags containing normal saline, manufactured and provided by Exela Pharma Sciences, LLC from a single batch / lot.
DRUGTranexamic Acid
Tranexamic Acid Intravenous Infusion Bags (10 mg/mL), manufactured and provided by Exela Pharma Sciences, LLC from a single batch / lot.
Sponsors
Exela Pharma Sciences, LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All adult patients (Male or Female) over age eighteen (\>18) electively undergoing complex spinal fusion surgery (defined as T2 to Pelvis/Sacrum and greater than 4 Functional Spinal Units (4 discs/motion segments=5 Vertebral segments). * Female subjects of childbearing potential with a negative serum (beta human chorionic gonadotropin \[HCG\]) pregnancy test at screening and urine pregnancy test at each admission; who are not breastfeeding; do not plan to become pregnant during the course of the study; and agree to use an approved method of birth control, such as condoms, foams, jellies, diaphragm, intrauterine device, sexual abstinence for at least 3 months prior to study * Able to provide written informed consent after risks and benefits of the study have been explained * Able to communicate effectively with study personnel.
Exclusion criteria
* History or presence of any clinically significant (based on the Investigator's judgment) cardiovascular, respiratory, metabolic, hepatic, gastrointestinal, renal, hematological, dermatological, neurological, or psychiatric disease or condition preventing the use of tranexamic acid * History of renal failure or elevated creatinine above 1.4 * Any diagnosis of spinal tumor or intradural pathology * Diagnosis of ankylosing spondylitis * History or presence of acquired disturbance of color vision * History of seizures * History of thromboembolic event (DVT or PE) within the past year * Current use of anticoagulant medications or past medical history leading to an abnormal coagulation profile preoperatively * Subjects diagnosed with fibrinolytic disorders requiring intra-operative antifibrinolytic treatment; hematological disease (thromboembolic events, hemoglobinopathy, coagulopathy, or hemolytic disease) * Significant drug sensitivity or significant allergic reaction to any drug, including tranexamic acid, based on the Investigator's judgment * A subject who has donated or lost 450 mL or more blood volume (including plasmaphoresis) or had a transfusion of any product within 3 months prior to the initial study drug administration * Pre-operative anemia (hb \<110 in females, Hb \<120 in males) * Any subject that chooses to refuse blood products for ethical or religious purposes (Jehovah's Witness) * Current participation in a drug or other investigational research study or participation within 30 days prior to the initial study drug administration * A subject who may not be able to comply with the safety monitoring requirements of this clinical trial or is considered by the investigator, for any reason, to be an unsuitable candidate for the study. * Intraoperative cardiovascular, pulmonary, orthopedic, or anesthetic complication such as myocardial infarction, intraoperative fracture, vasopressor support or emergent intubation. * Female patients who are using combination hormonal contraception. * Patients with history of subarachnoid hemorrhage. * Patients with serum creatinine above upper limit of normal (ULN).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Blood Loss | From time of surgery until discharge | The Total Blood Loss will be estimated based on the hemoglobin content of the blood prior to surgery (mg/dL) and at each of the desired post-surgery time-points (mg/dL). Blood samples for hemoglobin measurement will be collected prior to start of procedure, at the end of the procedure, at 24 h, and every 24 h thereafter until discharge and removal two subfascial drains. |
| Incidence of Autologous or Allogenic Blood Transfusion | From time of surgery until discharge | Number of Units of autologous transfusion and allogenic transfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Measured Blood Loss | From time of surgery up to 24 hours after surgery | Estimated as 3x cell saver |
| Number of Patients With Symptomatic Anemia Precipitated Transfusion | Until discharge | Number of patients with symptomatic anemia precipitated transfusion in each group |
| Number of Patients With Adverse Events Related to Tranexamic Acid | up to 6 weeks | Number of patients with adverse events related to tranexamic acid in each group |
Countries
United States
Participant flow
Recruitment details
Study terminated due to low recruitment
Pre-assignment details
Study terminated due to low recruitment
Participants by arm
| Arm | Count |
|---|---|
| Sodium Chloride 0.9% Sodium Chloride 0.9% infused at 3 mL/kg over one hour followed by continuous infusion at 0.3 mL/kg for maximum infusion volume of 5 mL/kg
Sodium Chloride 0.9% Inj: Inactive ingredient mixture for injection without drug, intravenous infusion bags containing normal saline, manufactured and provided by Exela Pharma Sciences, LLC from a single batch / lot. | 0 |
| Tranexamic Acid 10 mg/mL Tranexamic Acid 10 mg/mL infused at 3 mL/kg over one hour followed by continuous infusion at 0.3 mL/kg for maximum infusion volume of 5 mL/kg
Tranexamic Acid: Tranexamic Acid Intravenous Infusion Bags (10 mg/mL), manufactured and provided by Exela Pharma Sciences, LLC from a single batch / lot. | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence of Autologous or Allogenic Blood Transfusion
Number of Units of autologous transfusion and allogenic transfusion
Time frame: From time of surgery until discharge
Population: Study was terminated due to low recruitment. Data were not collected.
Primary
Total Blood Loss
The Total Blood Loss will be estimated based on the hemoglobin content of the blood prior to surgery (mg/dL) and at each of the desired post-surgery time-points (mg/dL). Blood samples for hemoglobin measurement will be collected prior to start of procedure, at the end of the procedure, at 24 h, and every 24 h thereafter until discharge and removal two subfascial drains.
Time frame: From time of surgery until discharge
Population: Data were not collected
Secondary
Number of Patients With Adverse Events Related to Tranexamic Acid
Number of patients with adverse events related to tranexamic acid in each group
Time frame: up to 6 weeks
Population: Total number of patients recruited and treated was 5 patients. No analyses were performed due to early termination of the study due to low recruitment.
Secondary
Number of Patients With Symptomatic Anemia Precipitated Transfusion
Number of patients with symptomatic anemia precipitated transfusion in each group
Time frame: Until discharge
Population: Total number of patients recruited and treated was 5 patients. No analyses were performed due to early termination of the study due to low recruitment.
Secondary
Total Measured Blood Loss
Estimated as 3x cell saver
Time frame: From time of surgery up to 24 hours after surgery
Population: Total number of patients recruited and treated was 5 patients. No analyses were performed due to early termination of the study due to low recruitment.