Total Knee Arthroplasty
Conditions
Brief summary
We are investigating the impact of duloxetine (Cymbalta), a serotonin and norepinephrine reuptake inhibitor, on pain after total knee arthroplasty (TKA). Specifically, the investigators will determine whether duloxetine, 60 mg daily for 2 weeks, reduces pain scores 2 weeks after TKA.
Interventions
DRUGPlacebo
Patients will receive placebo drug with no active ingredients per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14.
DRUGDuloxetine 60mg
Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14.
Sponsors
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with osteoarthritis scheduled for primary tricompartmental total knee arthroplasty with a participating surgeon * Age 25 to 75 years * Planned use of regional anesthesia * Ability to follow study protocol * English speaking (primary outcome obtained via telephone call and secondary outcomes include questionnaires validated in English only) * Patients planning on being discharged home or to a rehabilitation center that has agreed to participate
Exclusion criteria
* Concurrent use of duloxetine or other SNRIs, MAOIs, Tricyclic antidepressants, triptans (sumatriptan, rizatriptan, naratriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan), lithium, buspirone, St. John's Wort * Hepatic insufficiency * Renal insufficiency * Patients younger than 25 years old and older than 75 * Patients intending to receive general anesthesia * Allergy or intolerance to one of the study medications * Patients with an ASA of IV * Chronic gabapentin/pregabalin use (regular use for longer than 3 months) * Chronic opioid use (taking opioids for longer than 3 months) * Patients with major prior ipsilateral open knee surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NRS Pain With Ambulation at 2 Weeks | 2 weeks after surgery | When considering the pain in the knee in which you are having/had surgery, on a scale of 0-10, with 0 being no pain and 10 being pain as bad as you can imagine, how would you describe your level of pain in the last 24 hours during ambulation? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Opioid Use (mg Oral Morphine Equivalents) | POD 1 | Total daily opioid use (including PO, PCEA, IV, subcutaneous, IV push) in mg oral morphine equivalents on POD 1. |
| Nausea Severity | POD 1 | Nausea severity measured using Likert scale ranging from 0 (none) to 10 (severe). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken preoperatively. Starting on postoperative day (POD) 1, patients will take one capsule once a day until end of POD14.
Duloxetine 60mg: Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14. | 53 |
| Control Patients will receive 0mg of duloxetine
Placebo: Patients will receive placebo drug with no active ingredients per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14. | 53 |
| Total | 106 |
Baseline characteristics
| Characteristic | Duloxetine | Control | Total |
|---|---|---|---|
| Age, Continuous | 67 years | 63 years | 64 years |
| Body Mass Index | 31 kg/m^2 | 31 kg/m^2 | 31 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 46 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Knee pain severity with ambulation | 5.8 Units on a scale STANDARD_DEVIATION 2.5 | 5.2 Units on a scale STANDARD_DEVIATION 2.6 | 5.5 Units on a scale STANDARD_DEVIATION 2.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 48 Participants | 48 Participants | 96 Participants |
| Region of Enrollment United States | 53 participants | 53 participants | 106 participants |
| Sex: Female, Male Female | 28 Participants | 26 Participants | 54 Participants |
| Sex: Female, Male Male | 25 Participants | 27 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 53 |
| other Total, other adverse events | 4 / 53 | 3 / 53 |
| serious Total, serious adverse events | 0 / 53 | 0 / 53 |
Outcome results
Primary
NRS Pain With Ambulation at 2 Weeks
When considering the pain in the knee in which you are having/had surgery, on a scale of 0-10, with 0 being no pain and 10 being pain as bad as you can imagine, how would you describe your level of pain in the last 24 hours during ambulation?
Time frame: 2 weeks after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | NRS Pain With Ambulation at 2 Weeks | 3.5 NRS pain score | Standard Deviation 2.1 |
| Control | NRS Pain With Ambulation at 2 Weeks | 3.8 NRS pain score | Standard Deviation 2.3 |
Secondary
Nausea Severity
Nausea severity measured using Likert scale ranging from 0 (none) to 10 (severe).
Time frame: POD 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Nausea Severity | 0.9 units on a scale | Standard Deviation 2.2 |
| Control | Nausea Severity | 2.3 units on a scale | Standard Deviation 3.4 |
Secondary
Total Daily Opioid Use (mg Oral Morphine Equivalents)
Total daily opioid use (including PO, PCEA, IV, subcutaneous, IV push) in mg oral morphine equivalents on POD 1.
Time frame: POD 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Total Daily Opioid Use (mg Oral Morphine Equivalents) | 57.8 mg oral morphine equivalents | Standard Deviation 28.4 |
| Control | Total Daily Opioid Use (mg Oral Morphine Equivalents) | 72.7 mg oral morphine equivalents | Standard Deviation 34.9 |