Trial Outcomes & Findings for Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty (NCT NCT03271151)

NCT ID: NCT03271151

Last Updated: 2024-12-27

Results Overview

Opioid use (measured in cumulative morphine equivalents)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

160 participants

Primary outcome timeframe

Post-operative day 14

Results posted on

2024-12-27

Participant Flow

Participant milestones

Participant milestones
Measure
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
Placebo
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
Overall Study
STARTED
80
80
Overall Study
COMPLETED
78
77
Overall Study
NOT COMPLETED
2
3

Reasons for withdrawal

Reasons for withdrawal
Measure
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
Placebo
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
Overall Study
Lost to Follow-up
1
3
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Duloxetine ("Cymbalta")
n=80 Participants
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
Placebo
n=80 Participants
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
Total
n=160 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
41 Participants
n=5 Participants
42 Participants
n=7 Participants
83 Participants
n=5 Participants
Age, Categorical
>=65 years
39 Participants
n=5 Participants
38 Participants
n=7 Participants
77 Participants
n=5 Participants
Age, Continuous
63 years
STANDARD_DEVIATION 11 • n=5 Participants
64 years
STANDARD_DEVIATION 7 • n=7 Participants
63 years
STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male
Female
40 Participants
n=5 Participants
35 Participants
n=7 Participants
75 Participants
n=5 Participants
Sex: Female, Male
Male
40 Participants
n=5 Participants
45 Participants
n=7 Participants
85 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants
n=5 Participants
2 Participants
n=7 Participants
6 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
76 Participants
n=5 Participants
78 Participants
n=7 Participants
154 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Post-operative day 14

Opioid use (measured in cumulative morphine equivalents)

Outcome measures

Outcome measures
Measure
Duloxetine ("Cymbalta")
n=78 Participants
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
Placebo
n=77 Participants
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
Opioid Use
288 Oral Morphine Equivalent (mg)
Standard Deviation 226
432.5 Oral Morphine Equivalent (mg)
Standard Deviation 374

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Duloxetine ("Cymbalta")
n=78 Participants
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
Placebo
n=77 Participants
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
Pain Scores
4.2 score on a scale (NRS)
Standard Deviation 2
4.8 score on a scale (NRS)
Standard Deviation 2.2

SECONDARY outcome

Timeframe: Day of surgery

2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome.

Outcome measures

Outcome measures
Measure
Duloxetine ("Cymbalta")
n=80 Participants
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
Placebo
n=80 Participants
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
Pain Phenotype
2 score on a scale
Interval 1.0 to 4.0
2 score on a scale
Interval 1.0 to 4.0

Adverse Events

Duloxetine ("Cymbalta")

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Duloxetine ("Cymbalta")
n=80 participants at risk
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
Placebo
n=80 participants at risk
Placebo to compare pain scores and opioid use againts Duloxetine Placebo: Placebo to compare outcomes against Duloxetine
General disorders
Hallucinations
1.2%
1/80 • Number of events 1 • 3 months
1.2%
1/80 • Number of events 1 • 3 months
Reproductive system and breast disorders
Unable to Ejaculate
1.2%
1/80 • Number of events 1 • 3 months
0.00%
0/80 • 3 months
General disorders
Increased diaphoresis, blood pressure, complaints of diarrhea decreased unration and tooth pain
0.00%
0/80 • 3 months
1.2%
1/80 • Number of events 1 • 3 months
General disorders
Acne
0.00%
0/80 • 3 months
1.2%
1/80 • Number of events 1 • 3 months

Additional Information

Dr. Jacques Yadeau

Anesthesiology Critical Care & Pain Management

Phone: 2127742224

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place