Degenerative Disc Disease
Conditions
Keywords
Posterior Lumbar Interbody Fusion, Transforaminal Lumbar Interbody Fusion, Tranexamic Acid, Neurosurgery, Delirium
Brief summary
Tranexamic acid and placebo will be given during surgery to patients who have elected to undergo lumber interbody fusion on 2 or more levels. Information regarding blood loss, transfusions needed, postoperative cognitive status (including delirium), postoperative markers of systemic inflammation and duration of hospital stay will be collected.
Detailed description
This study is to assess whether tranexamic acid (a drug that is used to coagulate the blood and reduce bleeding) use in lumbar spinal fusion can reduce blood loss and postoperative delirium compared to placebo. Thusly reducing need for transfusion, shorting the hospital stay and improving outcomes. For this the study will randomize patients who are receiving elective lumbar interbody fusion (PLIF or TLIF) of 2 or more levels for degenerative disc disease (DDD) into 2 groups. Group 1 would receive tranexamic acid during the surgery while group 2 will receive placebo. Blood loss during the surgery and postoperatively (while the patient has a drain) will be monitored along with the amount of transfusions needed, postoperative cognitive status (including delirium), postoperative markers of systemic inflammation, and and the duration of hospital stay. Delirium occurrence and severity will be assessed daily for the first 5 days after surgery or at discharge, whichever comes first. Cognitive status (neuropsychological tests) will be assessed at post-discharge follow up visits and compared to preoperative status. The drug or placebo are only given during the surgery. The patient population includes elective cases of patient undergoing lumbar spinal fusion of 2 or more levels. Spinal fusions are known to be associated with blood loss, especially when the surgeries are long and more levels need to be fused.
Interventions
DRUGTranexamic Acid
Antifibrinolytic Agent
DRUGSaline Solution
Placebo
DIAGNOSTIC_TESTVisual Acuity Exam
Supplemented into standard of care daily neurological exam on day of surgery and day after
DIAGNOSTIC_TEST3 Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)
3D-CAM is a brief verbal assessment tool that can be used to test patients and study patients for delirium.
Sponsors
Catherine R. Olinger
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Phase 2B randomized, single-center, double-blinded, placebo vs treatment clinical trial with 1:1 randomization
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-90 years 2. American Spinal Injury Association (ASA) Impairment Scale anesthesia risk of I to IV 3. Patients undergoing 2 or more levels of posterior lumbar interbody fusion for DDD. This includes PLIF or TLIF. 4. Patients have failed conservative management, which include physical therapy (PT) or occupational therapy (OT) and/or injections.
Exclusion criteria
1. ASA class V 2. Patient unable to consent 3. Patient with chronic kidney disease stage III or above: baseline plasma creatinine\>1.5mg/dL 4. Patient with known liver failure 5. Patients on anticoagulation or dual antiplatelets (presence of vascular stents). 6. Patients with artificial valves. 7. Patients with allergy to TXA 8. Patients with platelet count \< 150 000, 9. Patients with PT\>15s 10. Patients with Activated Partial Thromboplastin Time (APPT) \>38s 11. History of stroke or (an) unprovoked thromboembolic event(s). 12. History of intracranial bleeding, 13. Pregnancy 14. known defective color vision 15. history of venous or arterial thromboembolism or active thromboembolic disease 16. Patients with severe pulmonary or cardiac disease. 17. Patients who refuse transfusion of blood products 18. Patients with chronic anemia with Hg\<8 19. Patients undergoing lumbar fusion for disease other than DDD (neoplasm) 20. Patients undergoing lumbar fusion by anterior or lateral approach. 21. Minimally invasive TLIF are excluded. 22. Emergent cases. 23. Women on hormonal contraception 24. Retinal vein or artery occlusion 25. Hypercoagulability 26. Seizure disorder 27. Current use of tretinoin 28. Current use of chlorpromazine 29. Breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transfusion | Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported | The number of participants who had red blood cells (RBC) transfused: 1. Intraoperatively 2. Postoperatively (prior to discharge or at day 5, whichever occurred first) 3. Either Intraoperatively or Postoperatively |
| Blood Loss | Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported | Amount of blood loss: 1. Intraoperatively 2. Postoperatively (prior to discharge or at day 5, whichever occurred first) 3. Either Intraoperatively or Postoperatively |
| Delirium Occurrence | Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported | Delirium occurrence (yes/no) using daily 3D-CAM delirium assessment instrument. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delirium Severity | Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported | Severity (score 0-20) using daily 3D-CAM delirium assessment instrument. Minimum=0 (no delirium) Maximum=20 (worse delirium) |
| Change in Interleukin-6 Concentration. | Preoperatively and 24 hours postoperatively | Measure of systemic inflammation using Interleukin-6 change between preoperative and 24 postoperatively blood draw. |
| Length of Postoperative Stay Prior to Discharge | Days thru day of discharge | Length of postoperative stay prior to discharge in days |
Countries
United States
Participant flow
Recruitment details
123 subjects were enrolled and consented. Prior to randomization, 37 subjects were excluded and did not get randomized.
Pre-assignment details
37 subjects were excluded and not randomized due to the following reasons: * Exclusion criteria was found (14 subjects) * Surgery cancelled (8 subjects) * Subjects withdrew (5 subjects) * Surgery changed to min invasive and so subject did not qualify (3 subjects) * Surgeon decision (2 subjects) * trial on hold during randomization period (2 subjects) * study medication order problems (3 subjects)
Participants by arm
| Arm | Count |
|---|---|
| Treatment 1:1 randomization, given tranexamic acid during surgery, visual acuity exam
Tranexamic Acid: Antifibrinolytic Agent
Visual Acuity Exam: Supplemented into standard of care daily neurological exam on day of surgery and day after
3 Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM): 3D-CAM is a brief verbal assessment tool that can be used to test patients and study patients for delirium. | 43 |
| Placebo 1:1 randomization, given standard of care treatment during surgery, visual acuity exam
Saline Solution: Placebo
Visual Acuity Exam: Supplemented into standard of care daily neurological exam on day of surgery and day after
3 Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM): 3D-CAM is a brief verbal assessment tool that can be used to test patients and study patients for delirium. | 40 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Treatment | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 19 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 21 Participants | 47 Participants |
| Age, Continuous | 59 years | 63 years | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 37 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 38 Participants | 78 Participants |
| Region of Enrollment United States | 43 participants | 40 participants | 83 participants |
| Sex: Female, Male Female | 20 Participants | 22 Participants | 42 Participants |
| Sex: Female, Male Male | 23 Participants | 18 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 40 |
| other Total, other adverse events | 6 / 43 | 6 / 40 |
| serious Total, serious adverse events | 0 / 43 | 2 / 40 |
Outcome results
Primary
Blood Loss
Amount of blood loss: 1. Intraoperatively 2. Postoperatively (prior to discharge or at day 5, whichever occurred first) 3. Either Intraoperatively or Postoperatively
Time frame: Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment | Blood Loss | Intraoperatively | 167 ml per instrumented vertebral level |
| Treatment | Blood Loss | Postoperatively (prior to discharge or at day 5, whichever occurred first) | 128 ml per instrumented vertebral level |
| Treatment | Blood Loss | Either Intraoperatively or Postoperatively | 305 ml per instrumented vertebral level |
| Placebo | Blood Loss | Intraoperatively | 110 ml per instrumented vertebral level |
| Placebo | Blood Loss | Postoperatively (prior to discharge or at day 5, whichever occurred first) | 207 ml per instrumented vertebral level |
| Placebo | Blood Loss | Either Intraoperatively or Postoperatively | 333 ml per instrumented vertebral level |
Primary
Delirium Occurrence
Delirium occurrence (yes/no) using daily 3D-CAM delirium assessment instrument.
Time frame: Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Delirium Occurrence | 7 participants with delirium |
| Placebo | Delirium Occurrence | 11 participants with delirium |
Primary
Transfusion
The number of participants who had red blood cells (RBC) transfused: 1. Intraoperatively 2. Postoperatively (prior to discharge or at day 5, whichever occurred first) 3. Either Intraoperatively or Postoperatively
Time frame: Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Transfusion | Postoperatively (prior to discharge or at day 5, whichever occurred first) | 9 Participants |
| Treatment | Transfusion | Either Intraoperatively or Postoperatively | 10 Participants |
| Treatment | Transfusion | Intraoperatively | 7 Participants |
| Placebo | Transfusion | Intraoperatively | 6 Participants |
| Placebo | Transfusion | Postoperatively (prior to discharge or at day 5, whichever occurred first) | 8 Participants |
| Placebo | Transfusion | Either Intraoperatively or Postoperatively | 10 Participants |
Secondary
Change in Interleukin-6 Concentration.
Measure of systemic inflammation using Interleukin-6 change between preoperative and 24 postoperatively blood draw.
Time frame: Preoperatively and 24 hours postoperatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Change in Interleukin-6 Concentration. | 25.7 pg per ml |
| Placebo | Change in Interleukin-6 Concentration. | 10.6 pg per ml |
Secondary
Delirium Severity
Severity (score 0-20) using daily 3D-CAM delirium assessment instrument. Minimum=0 (no delirium) Maximum=20 (worse delirium)
Time frame: Assessed up to 5 days or until discharge, whichever came first, data collected on discharge day or day 5 reported
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Delirium Severity | 1.10 3D-CAM Points |
| Placebo | Delirium Severity | 1.00 3D-CAM Points |
Secondary
Length of Postoperative Stay Prior to Discharge
Length of postoperative stay prior to discharge in days
Time frame: Days thru day of discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Length of Postoperative Stay Prior to Discharge | 3 Days |
| Placebo | Length of Postoperative Stay Prior to Discharge | 3 Days |