Effects of Pregabalin on Pain After Total Knee Arthroplasty

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Pregabalin on Pain After Total Knee Arthroplasty: A Randomized, Controlled, Double-Blind Trial

Conditions
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Primary Total Knee Arthroplasty

Intervention / Treatment
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* Drug: Pregabalin 50mg
* Drug: Pregabalin 100mg
* Drug: Pregabalin 150mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Patients will receive 0mg of pregabalin | Drug: Placebo<br>* 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.<br>|
| Experimental: 50mg Arm<br>Patients will receive 50mg of pregabalin per dose. 2 capsules will be taken pre-operatively. One capsule twice a day until end of post-operative day (POD)14 and one capsule at bedtime POD15, POD16. | Drug: Pregabalin 50mg<br>* 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.<br>* Other names: Lyrica;|
| Experimental: 100mg Arm<br>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. | Drug: Pregabalin 100mg<br>* 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.<br>* Other names: Lyrica;|
| Experimental: 150mg Arm<br>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. | Drug: Pregabalin 150mg<br>* 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.<br>* Other names: Lyrica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Pain | Pain assessment scale (Numeric Rating Scale) (0=no pain; 10=worst pain imaginable). | 2 weeks postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 2 weeks postoperatively | 
| Self-assessed Sedation and Confusion | Self-assessed sedation and confusion (POD1). Confusion Assessment Method (CAM score) (pre-operative and on POD1) | 1 day postoperatively | 
| 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) | 3 months | 
| 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. | 3 months | 
| Opioid Usage | Opioid Usage (POD1, POD 3, 2 weeks, 3 months) | 3 months | 
| Satisfaction | Satisfaction with pain management (1-10 scale; 1 = very dissatisfied, 10 = very satisfied) | 2 weeks |