Joint Disease, Pain, Acute, Pain, Chronic
Conditions
Brief summary
Post-discharge pain after total knee arthroplasty remains problematic; many patients have excessive pain at the 2 week time point (and often thereafter). Reduction in opioid use has become a national goal, due to the 'epidemic' in opioid misuse. In addition to enrolling non-opioid users, we will enroll up to 15 chronic opioid users.
Interventions
DRUGCymbalta
Duloxetine (Cymbalta) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain
OTHERPlacebo
Placebo to compare outcomes against Duloxetine
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
* 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
* Current Use of duloxetine or other SNRIs, SSRIs, MAOIs, Tricyclic antidepressants, triptans (sumatriptan, rizatriptan, naratriptan, eletriptan, almotriptan, frovatriptan), lithium, buspirone, St. John's Wort * Hepatic insufficiency o Hepatoxicity is reported as a side effect of duloxetine. Median time to detection of transaminase elevation was about two months (package insert 5.2 * Renal insufficiency (ESRD, HD, estimated creatinine clearance \< 50 ml/min) * Severe CRI may impair duloxetine clearance * CLcr=\[(140-age (years)\] x weight (kg)x0.85 (for female patients)/\[72xserum creatinine (mg/dL)\] * 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) * Patients with major prior ipsilateral open knee surgery. * Chronic opioid use (taking opioids for longer than 3 months) * However, patients using chronic opioids may enroll in a parallel pilot study entitled 'effect of duloxetine on opioid use after total knee athroplasty among patients exposed to opioids- a pilot study'. The chronic opioid users will be allowed to continue their customary analgesics. The pilot study is otherwise identical to the main study. * This study will enroll up to 15 chronic opioid users. After that, all chronic opioid users are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Use | Post-operative day 14 | Opioid use (measured in cumulative morphine equivalents) |
| Pain Scores | Post-operative day 14 | Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Phenotype | Day of surgery | 2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine (Cymbalta) Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (Cymbalta) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia.
Cymbalta: Duloxetine (Cymbalta) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain | 80 |
| Placebo Placebo to compare pain scores and opioid use againts Duloxetine
Placebo: Placebo to compare outcomes against Duloxetine | 80 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Duloxetine (Cymbalta) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 39 Participants | 38 Participants | 77 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 42 Participants | 83 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 11 | 64 years STANDARD_DEVIATION 7 | 63 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 78 Participants | 154 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 40 Participants | 35 Participants | 75 Participants |
| Sex: Female, Male Male | 40 Participants | 45 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 80 |
| other Total, other adverse events | 2 / 80 | 3 / 80 |
| serious Total, serious adverse events | 0 / 80 | 0 / 80 |
Outcome results
Primary
Opioid Use
Opioid use (measured in cumulative morphine equivalents)
Time frame: Post-operative day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Opioid Use | 288 Oral Morphine Equivalent (mg) | Standard Deviation 226 |
| Placebo | Opioid Use | 432.5 Oral Morphine Equivalent (mg) | Standard Deviation 374 |
Primary
Pain Scores
Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome.
Time frame: Post-operative day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Pain Scores | 4.2 score on a scale (NRS) | Standard Deviation 2 |
| Placebo | Pain Scores | 4.8 score on a scale (NRS) | Standard Deviation 2.2 |
Secondary
Pain Phenotype
2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.
Time frame: Day of surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duloxetine (Cymbalta) | Pain Phenotype | 2 score on a scale |
| Placebo | Pain Phenotype | 2 score on a scale |