Effects of Pregabalin on Pain After Total Knee Arthroplasty

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Total Knee Arthroplasty
• Intervention / Treatment: Drug: Placebo; Drug: Pregabalin 50mg; Drug: Pregabalin 100mg; Drug: Pregabalin 150mg

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control; Patients will receive 0mg of pregabalin	Drug: 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.
EXPERIMENTAL: 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 post-operative day (POD)14 and one capsule at bedtime POD15, POD16.	Drug: 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.; Other Names: Lyrica
EXPERIMENTAL: 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.	Drug: 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.; Other Names: Lyrica
EXPERIMENTAL: 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.	Drug: 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.; Other Names: Lyrica

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York

Publications and helpful links

General Publications

• YaDeau JT, Lin Y, Mayman DJ, Goytizolo EA, Alexiades MM, Padgett DE, Kahn RL, Jules-Elysee KM, Ranawat AS, Bhagat DD, Fields KG, Goon AK, Curren J, Westrich GH. Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial. Br J Anaesth. 2015 Aug;115(2):285-93. doi: 10.1093/bja/aev217.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: April 8, 2011
• First Submitted That Met QC Criteria: April 11, 2011
• First Posted (ESTIMATE): April 12, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 18, 2016
• Last Update Submitted That Met QC Criteria: April 12, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 11043