Primary Total Knee Arthroplasty
Conditions
Brief summary
Total knee arthroplasty can cause severe postoperative pain, and patients typically receive oral opioid analgesics for over 2 weeks. Side effects of pain management may impair participation in physical therapy and diminish patient satisfaction. Anecdotally, it seems that pregabalin is very helpful to patients after total knee arthroplasty. However, pregabalin can have side effects. It is not clear how much pregabalin to prescribe. Low doses may not be effective, but use of high doses may increase the incidence and severity of side effects.The purpose of this study is to determine which dosage of pregabalin is the most effective at reducing pain after knee surgery.
Interventions
DRUGPregabalin 50mg
Patients will receive 50mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
DRUGPregabalin 100mg
Patients will receive 100mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
DRUGPregabalin 150mg
Patients will receive 150mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
DRUGPlacebo
Patients will receive placebo drug with no active ingredients per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
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
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with osteoarthritis scheduled for primary tricompartmental total knee arthroplasty with a participating surgeon * Age 18 to 80 years old * 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
* Patients younger than 18 years old and older than 80 * Patients intending to receive general anesthesia * Allergy or intolerance to one of the study medications * Patients with an ASA of IV * Patients with hepatic (liver) failure * Patients with chronic renal (kidney) failure (Defined as estimated creatinine clearance \< 30 mL/min, based on recommendation that total daily pregabalin dose be reduced to 150 mg with Clcr \< 30 mL/min, CLcr=\[(140-age (years)\] x weight (kg)x0.85 (for female patients)/\[72xserum creatinine (mg/dL)\]) * Patients with difficult to manage diabetes mellitus, including insulin-dependence * 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. * Chronic neurontin/lyrica use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Pain | 2 weeks postoperatively | Pain assessment scale (Numeric Rating Scale) (0=no pain; 10=worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Self-assessed Sedation and Confusion | 1 day postoperatively | Self-assessed sedation and confusion (POD1). Confusion Assessment Method (CAM score) (pre-operative and on POD1) |
| Numeric Rating Scale (NRS) | 3 months | NRS Pain (pre-operative, POD1, POD3, 2 weeks, 3 months, at orthopedic visits). Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months) |
| Opioid-Related Symptom Distress Score | 2 weeks postoperatively | Opioid-Related Symptom Distress score (ORSDS) measured at POD1 and POD14. The ORSDS is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 12 symptom-specific scores. (0=low; 4=high). |
| Opioid Usage | 3 months | Opioid Usage (POD1, POD 3, 2 weeks, 3 months) |
| Satisfaction | 2 weeks | Satisfaction with pain management (1-10 scale; 1 = very dissatisfied, 10 = very satisfied) |
| Neuropathic Pain | 3 months | Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months). Scale of 0 to 24. Higher values represent worse outcomes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Patients will receive 0mg of pregabalin
Placebo: Patients will receive placebo drug with no active ingredients per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16. | 30 |
| 50mg Arm Patients will receive 50mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Pregabalin 50mg: Patients will receive 50mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16. | 30 |
| 100mg Arm Patients will receive 100mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Pregabalin 100mg: Patients will receive 100mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16. | 30 |
| 150mg Arm Patients will receive 150mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16.
Pregabalin 150mg: Patients will receive 150mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of POD14 and one capsule at bedtime POD15, POD16. | 30 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 1 |
| Overall Study | Unable to complete study procedure | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Control | 50mg Arm | 100mg Arm | 150mg Arm | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 9.8 | 66.8 years STANDARD_DEVIATION 6.3 | 65.1 years STANDARD_DEVIATION 7.1 | 67.7 years STANDARD_DEVIATION 8.1 | 66.3 years STANDARD_DEVIATION 7.9 |
| Body Mass Index (BMI) | 32 kg/m ^ 2 STANDARD_DEVIATION 5 | 32 kg/m ^ 2 STANDARD_DEVIATION 6 | 32 kg/m ^ 2 STANDARD_DEVIATION 6 | 30 kg/m ^ 2 STANDARD_DEVIATION 7 | 31.5 kg/m ^ 2 STANDARD_DEVIATION 2.45 |
| Region of Enrollment United States | 30 participants | 30 participants | 30 participants | 30 participants | 120 participants |
| Sex: Female, Male Female | 14 Participants | 18 Participants | 13 Participants | 23 Participants | 68 Participants |
| Sex: Female, Male Male | 16 Participants | 12 Participants | 17 Participants | 7 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Postoperative Pain
Pain assessment scale (Numeric Rating Scale) (0=no pain; 10=worst pain imaginable).
Time frame: 2 weeks postoperatively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Postoperative Pain | POD14 Pain score with flexion | 4 units on a scale | Standard Deviation 2.3 |
| Control | Postoperative Pain | POD14 Pain score at rest | 2.9 units on a scale | Standard Deviation 2.3 |
| Control | Postoperative Pain | POD14 Pain score with ambulation | 3.6 units on a scale | Standard Deviation 2 |
| 50mg Arm | Postoperative Pain | POD14 Pain score with flexion | 4.8 units on a scale | Standard Deviation 2.1 |
| 50mg Arm | Postoperative Pain | POD14 Pain score at rest | 2.9 units on a scale | Standard Deviation 2 |
| 50mg Arm | Postoperative Pain | POD14 Pain score with ambulation | 3.8 units on a scale | Standard Deviation 1.6 |
| 100mg Arm | Postoperative Pain | POD14 Pain score with ambulation | 3.5 units on a scale | Standard Deviation 1.8 |
| 100mg Arm | Postoperative Pain | POD14 Pain score with flexion | 4.5 units on a scale | Standard Deviation 2.4 |
| 100mg Arm | Postoperative Pain | POD14 Pain score at rest | 2.8 units on a scale | Standard Deviation 1.8 |
| 150mg Arm | Postoperative Pain | POD14 Pain score with flexion | 4.0 units on a scale | Standard Deviation 2.1 |
| 150mg Arm | Postoperative Pain | POD14 Pain score at rest | 2.7 units on a scale | Standard Deviation 2.1 |
| 150mg Arm | Postoperative Pain | POD14 Pain score with ambulation | 3.1 units on a scale | Standard Deviation 1.9 |
Secondary
Neuropathic Pain
Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months). Scale of 0 to 24. Higher values represent worse outcomes.
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Neuropathic Pain | 0 units on a scale |
| 50mg Arm | Neuropathic Pain | 0 units on a scale |
| 100mg Arm | Neuropathic Pain | 0 units on a scale |
| 150mg Arm | Neuropathic Pain | 0 units on a scale |
Secondary
Numeric Rating Scale (NRS)
NRS Pain (pre-operative, POD1, POD3, 2 weeks, 3 months, at orthopedic visits). Neuropathic pain incidence: Leeds assessment of neuropathic symptoms and signs (LANSS) score (3 months)
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control | Numeric Rating Scale (NRS) | POD14 NRS Pain Score with Flexion | 4 units on a scale |
| Control | Numeric Rating Scale (NRS) | POD1 NRS Pain Score with Flexion | 2.8 units on a scale |
| Control | Numeric Rating Scale (NRS) | 3 months NRS Pain Score with Flexion | 2 units on a scale |
| Control | Numeric Rating Scale (NRS) | POD3 NRS Pain Score with Flexion | 3.9 units on a scale |
| Control | Numeric Rating Scale (NRS) | Preop NRS Pain Score with Flexion | 4.9 units on a scale |
| 50mg Arm | Numeric Rating Scale (NRS) | POD3 NRS Pain Score with Flexion | 4.2 units on a scale |
| 50mg Arm | Numeric Rating Scale (NRS) | POD14 NRS Pain Score with Flexion | 4.9 units on a scale |
| 50mg Arm | Numeric Rating Scale (NRS) | 3 months NRS Pain Score with Flexion | 1.9 units on a scale |
| 50mg Arm | Numeric Rating Scale (NRS) | POD1 NRS Pain Score with Flexion | 2.9 units on a scale |
| 50mg Arm | Numeric Rating Scale (NRS) | Preop NRS Pain Score with Flexion | 5.4 units on a scale |
| 100mg Arm | Numeric Rating Scale (NRS) | POD3 NRS Pain Score with Flexion | 3.6 units on a scale |
| 100mg Arm | Numeric Rating Scale (NRS) | Preop NRS Pain Score with Flexion | 3.9 units on a scale |
| 100mg Arm | Numeric Rating Scale (NRS) | POD1 NRS Pain Score with Flexion | 2.7 units on a scale |
| 100mg Arm | Numeric Rating Scale (NRS) | POD14 NRS Pain Score with Flexion | 4.5 units on a scale |
| 100mg Arm | Numeric Rating Scale (NRS) | 3 months NRS Pain Score with Flexion | 1.7 units on a scale |
| 150mg Arm | Numeric Rating Scale (NRS) | POD14 NRS Pain Score with Flexion | 4.2 units on a scale |
| 150mg Arm | Numeric Rating Scale (NRS) | POD1 NRS Pain Score with Flexion | 2.5 units on a scale |
| 150mg Arm | Numeric Rating Scale (NRS) | Preop NRS Pain Score with Flexion | 5.7 units on a scale |
| 150mg Arm | Numeric Rating Scale (NRS) | POD3 NRS Pain Score with Flexion | 4.3 units on a scale |
| 150mg Arm | Numeric Rating Scale (NRS) | 3 months NRS Pain Score with Flexion | 1.8 units on a scale |
Secondary
Opioid-Related Symptom Distress Score
Opioid-Related Symptom Distress score (ORSDS) measured at POD1 and POD14. The ORSDS is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 12 symptom-specific scores. (0=low; 4=high).
Time frame: 2 weeks postoperatively
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control | Opioid-Related Symptom Distress Score | ORSDS POD1 | .4 units on a scale |
| Control | Opioid-Related Symptom Distress Score | ORSDS POD14 | .3 units on a scale |
| 50mg Arm | Opioid-Related Symptom Distress Score | ORSDS POD14 | .3 units on a scale |
| 50mg Arm | Opioid-Related Symptom Distress Score | ORSDS POD1 | .4 units on a scale |
| 100mg Arm | Opioid-Related Symptom Distress Score | ORSDS POD1 | .5 units on a scale |
| 100mg Arm | Opioid-Related Symptom Distress Score | ORSDS POD14 | .3 units on a scale |
| 150mg Arm | Opioid-Related Symptom Distress Score | ORSDS POD1 | .4 units on a scale |
| 150mg Arm | Opioid-Related Symptom Distress Score | ORSDS POD14 | .3 units on a scale |
Secondary
Opioid Usage
Opioid Usage (POD1, POD 3, 2 weeks, 3 months)
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control | Opioid Usage | Preop Total Opioid Use (mg) | 19 mg |
| Control | Opioid Usage | POD 1 Total Opioid Use (mg) | 50 mg |
| Control | Opioid Usage | POD 2 Total Opioid Use (mg) | 70 mg |
| Control | Opioid Usage | POD 3 Total Opioid Use (mg) | 55 mg |
| Control | Opioid Usage | POD 14 Total Opioid Use (mg) | 40 mg |
| Control | Opioid Usage | 3 months Total Opioid Use (mg) | 0 mg |
| 50mg Arm | Opioid Usage | 3 months Total Opioid Use (mg) | 3 mg |
| 50mg Arm | Opioid Usage | POD 3 Total Opioid Use (mg) | 60 mg |
| 50mg Arm | Opioid Usage | Preop Total Opioid Use (mg) | 18 mg |
| 50mg Arm | Opioid Usage | POD 2 Total Opioid Use (mg) | 60 mg |
| 50mg Arm | Opioid Usage | POD 1 Total Opioid Use (mg) | 46 mg |
| 50mg Arm | Opioid Usage | POD 14 Total Opioid Use (mg) | 36 mg |
| 100mg Arm | Opioid Usage | POD 1 Total Opioid Use (mg) | 57 mg |
| 100mg Arm | Opioid Usage | POD 2 Total Opioid Use (mg) | 63 mg |
| 100mg Arm | Opioid Usage | POD 3 Total Opioid Use (mg) | 40 mg |
| 100mg Arm | Opioid Usage | 3 months Total Opioid Use (mg) | 0 mg |
| 100mg Arm | Opioid Usage | POD 14 Total Opioid Use (mg) | 40 mg |
| 100mg Arm | Opioid Usage | Preop Total Opioid Use (mg) | 17 mg |
| 150mg Arm | Opioid Usage | POD 14 Total Opioid Use (mg) | 45 mg |
| 150mg Arm | Opioid Usage | 3 months Total Opioid Use (mg) | 4 mg |
| 150mg Arm | Opioid Usage | POD 1 Total Opioid Use (mg) | 45 mg |
| 150mg Arm | Opioid Usage | POD 3 Total Opioid Use (mg) | 36 mg |
| 150mg Arm | Opioid Usage | Preop Total Opioid Use (mg) | 18 mg |
| 150mg Arm | Opioid Usage | POD 2 Total Opioid Use (mg) | 55 mg |
Secondary
Satisfaction
Satisfaction with pain management (1-10 scale; 1 = very dissatisfied, 10 = very satisfied)
Time frame: 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Satisfaction | 9 units on a scale |
| 50mg Arm | Satisfaction | 8 units on a scale |
| 100mg Arm | Satisfaction | 8 units on a scale |
| 150mg Arm | Satisfaction | 8 units on a scale |
Secondary
Self-assessed Sedation and Confusion
Self-assessed sedation and confusion (POD1). Confusion Assessment Method (CAM score) (pre-operative and on POD1)
Time frame: 1 day postoperatively
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Self-assessed Sedation and Confusion | Drowsiness POD1 [ORSDS] | 34.5 percentage of patients |
| Control | Self-assessed Sedation and Confusion | Nausea POD1 [ORSDS] | 34.5 percentage of patients |
| 50mg Arm | Self-assessed Sedation and Confusion | Nausea POD1 [ORSDS] | 41.4 percentage of patients |
| 50mg Arm | Self-assessed Sedation and Confusion | Drowsiness POD1 [ORSDS] | 37.9 percentage of patients |
| 100mg Arm | Self-assessed Sedation and Confusion | Drowsiness POD1 [ORSDS] | 55.2 percentage of patients |
| 100mg Arm | Self-assessed Sedation and Confusion | Nausea POD1 [ORSDS] | 44.8 percentage of patients |
| 150mg Arm | Self-assessed Sedation and Confusion | Drowsiness POD1 [ORSDS] | 58.6 percentage of patients |
| 150mg Arm | Self-assessed Sedation and Confusion | Nausea POD1 [ORSDS] | 31.0 percentage of patients |