Osteoarthritis, Knee
Conditions
Keywords
Total knee arthroplasty, Total joint arthroplasty, Knee replacement, Osteoarthritis of the knee
Brief summary
The purpose of this study is to determine whether liposomal bupivacaine is effective in the management of pain following total knee arthroplasty, as compared to standard of care analgesia.
Detailed description
Liposomal bupivacaine (Exparel®) is a local anesthetic made up of liposomal encapsulated bupivacaine. It is designed to be injected at the time of surgery into the local soft tissues. Because of its unique liposomal delivery system, Liposomal bupivacaine (Exparel®) has been shown to provide up to 96 hours of pain relief following surgeries. This makes it an attractive option in total knee arthroplasty patients. Combined with the proven efficacy of regional anesthesia, intraoperative liposomal bupivacaine (Exparel®) may provide extended pain relief following total knee arthroplasty. This has the potential to avoid the need for opioid medications. With better pain control, medication side effects can be avoided and patient's length of stay in the hospital can be shortened.
Interventions
DRUGLiposomal bupivacaine
DRUGStandard of Care
Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.
Sponsors
OhioHealth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age * Scheduled to undergo total knee arthroplasty (TKA) performed by the principal investigator
Exclusion criteria
* Age \<18 years * Pregnant or breastfeeding * Non-English-speaking * Unable to give informed consent * Patients admitted from or discharged to a medical facility (due to likelihood of limited mobility and/or required minimum lengths of stay, confounding primary outcome), including other hospitals, skilled nursing facilities, long-term acute care hospitals, etc. * Patients unable to complete a device-assisted 140 foot walk at baseline * Patients with contraindication(s) to any bupivacaine or ropivacaine formulation, to nerve blocks or any of the local agents used (IV morphine, ketorolac, or methylprednisolone). * Patients on a long-acting maintenance opioid prior to admission for surgery (e.g., methadone, oxycontin) * Patients undergoing simultaneous bilateral TKAs, as this would increase the dose of Exparel per patient (we are limited to one dose per patient)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Physical Therapy Sessions Necessary for Discharge | Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days. | Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Stay (LOS, in Days) | Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days. | — |
| Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams) | Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days. | — |
| Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay | Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days. | VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated |
| Total Cost of Care (Dollars) | Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days. | — |
| Hospital Readmission Not Including Admissions Planned Procedures | Participants will be followed for 30 days after leaving the hospital. | — |
| Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay | Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days. | 1. Nausea 2. Vomiting 3. Constipation 4. Ileus 5. Pruritus 6. Respiratory depression 7. Over-sedation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liposomal Bupivacaine Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Liposomal bupivacaine (diluted to 60mL): 20mL into the posterior pocket, 20mL into the lateral, and 20mL into the medial, including all deep and superficial tissues of these areas.
Liposomal bupivacaine | 30 |
| Standard of Care Pre-operative adductor canal nerve block (20mL of 0.5% ropivacaine). Intra-operative popliteal nerve block from the surgeon: 20mL 0.2% ropivacaine and a peri-articular injection of 10mg morphine, 30mg ketorolac and 40mg methylprednisolone.
ropivacaine, morphine ,ketorolac, methylprednisolone: Standard of care analgesia | 29 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Randomization envelope pulled out of seq | 0 | 1 |
Baseline characteristics
| Characteristic | Liposomal Bupivacaine | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 8.3 | 61.2 years STANDARD_DEVIATION 8.9 | 63.1 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 30 | 11 / 29 |
| serious Total, serious adverse events | 0 / 30 | 0 / 29 |
Outcome results
Primary
Number Physical Therapy Sessions Necessary for Discharge
Number of physical therapy (PT) sessions necessary for discharge. A significant decrease in the number of sessions will be defined as ≥ 2. Typically, there are 2 sessions per day, with each patient completing an average of 4-5 sessions during their admission.
Time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Number Physical Therapy Sessions Necessary for Discharge | 3.0 Physical Therapy Sessions | Standard Deviation 1.2 |
| Standard of Care | Number Physical Therapy Sessions Necessary for Discharge | 3.6 Physical Therapy Sessions | Standard Deviation 1.3 |
p-value: 0.137t-test, 2 sided
Secondary
Hospital Readmission Not Including Admissions Planned Procedures
Time frame: Participants will be followed for 30 days after leaving the hospital.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liposomal Bupivacaine | Hospital Readmission Not Including Admissions Planned Procedures | 0 participants |
| Standard of Care | Hospital Readmission Not Including Admissions Planned Procedures | 1 participants |
Secondary
Length of Stay (LOS, in Days)
Time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Length of Stay (LOS, in Days) | 2.5 Days | Standard Deviation 0.8 |
| Standard of Care | Length of Stay (LOS, in Days) | 2.3 Days | Standard Deviation 0.5 |
p-value: 0.208t-test, 2 sided
Secondary
Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay
VAS was measured using a scale that ranged from 0 to 10. Higher scores indicate more pain, or a worse outcome. Patients had pain measured a variable number of times following surgery before discharge. Mean VAS score during the hospital stay for each patient was calculated
Time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay | 4.4 Units on a scale | Standard Deviation 1.3 |
| Standard of Care | Mean Visual Analog Scale (VAS) Pain Scores During Hospital Stay | 4.7 Units on a scale | Standard Deviation 1.5 |
p-value: 0.343t-test, 2 sided
Secondary
Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay
1. Nausea 2. Vomiting 3. Constipation 4. Ileus 5. Pruritus 6. Respiratory depression 7. Over-sedation
Time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liposomal Bupivacaine | Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay | 13 participants |
| Standard of Care | Number of Participants With Opioid-related Adverse Events (ORAEs) During Hospital Stay | 11 participants |
p-value: 0.843Chi-squared
Secondary
Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams)
Time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams) | 274.6 Milligrams | Standard Deviation 121 |
| Standard of Care | Opioid Consumption in Oral Morphine Equivalents (OMEs, in Milligrams) | 304.8 Milligrams | Standard Deviation 143.4 |
p-value: 0.385t-test, 2 sided
Secondary
Total Cost of Care (Dollars)
Time frame: Participants will be followed for the duration of their hospital stay, an expected average of 2.5 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liposomal Bupivacaine | Total Cost of Care (Dollars) | 64582.90 Dollars |
| Standard of Care | Total Cost of Care (Dollars) | 62601.50 Dollars |
p-value: 0.438Wilcoxon (Mann-Whitney)