Effects of Pregabalin on Pain After Total Knee Arthroplasty

Phase 1

Completed

Interventions: Drug: Pregabalin 50mg
Drug: Placebo
Drug: Pregabalin 100mg
Drug: Pregabalin 150mg

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
50mg Arm	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 post-operative day (POD)14 and one capsule at bedtime POD15, POD16.
Control	Placebo	Patients will receive 0mg of pregabalin
100mg Arm	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.
150mg Arm	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.

Primary Outcome Measures

Name	Time	Method
Postoperative Pain	2 weeks postoperatively	Pain assessment scale (Numeric Rating Scale) (0=no pain; 10=worst pain imaginable).

Secondary Outcome Measures

Name	Time	Method
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).
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)
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.
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)