Prospective, Randomized Controlled Trial on Perioperative Pregabalin to Reduce Late-onset CRPS After TKA

Study Overview
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Brief Summary
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The Department of Anesthesiology is conducting a clinical trial to evaluate if pregabalin given prior to and for several days after Total Knee Arthroplasty (TKA) will reduce the prevalence of Complex Regional Pain Syndrome (CRPS) at late postoperative times. The prevalence of complex regional pain syndrome (CRPS) following total knee arthroplasty (TKA) is 13% at 6 months post-surgery. CRPS is a painful debilitating condition, with 4 main classes of symptoms : sensory, including burning, allodynia, and hyperalgesia in the affected limb; vasomotor, including temperature asymmetry and skin color changes; edema and sudomotor, including sweating; and movement disorders and dystrophy, including decreased range of motion, motor dysfunction (weakness, tremor, dystonia) and changes in hair, nails or skin.

Detailed Description
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The Department of Anesthesiology is conducting a clinical trial to evaluate if pregabalin given prior to and for several days after Total Knee Arthroplasty (TKA) will reduce the prevalence of Complex Regional Pain Syndrome (CRPS) at late postoperative times. The prevalence of complex regional pain syndrome (CRPS) following total knee arthroplasty (TKA) is 13% at 6 months post-surgery. CRPS is a painful debilitating condition, with 4 main classes of symptoms : sensory, including burning, allodynia, and hyperalgesia in the affected limb; vasomotor, including temperature asymmetry and skin color changes; edema and sudomotor, including sweating; and movement disorders and dystrophy, including decreased range of motion, motor dysfunction (weakness, tremor, dystonia) and changes in hair, nails or skin. Gabapentin and the related more potent compound pregabalin have been shown to reduce postoperative pain in animal models. Pregabalin also reduces neuropathic pain in rats. In patients, gabapentin has been administered before surgery to treat postoperative pain. In addition, pregabalin has been given postoperatively to reduce dental pain after molar extraction. Gabapentin has been used for many years in patients with neuropathic pain, including reflex sympathetic dystrophy. More recently, pregabalin has also been shown to be efficacious in the treatment of neuropathic pain. However, no clinical study has investigated whether perioperative administration of gabapentin or pregabalin can reduce persistent long-term pain syndromes e.g. CRPS.Subjects between the ages of 21 and 80 will be recruited after obtaining an Informed Consent.

Official Title
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A Prospective, Randomized Controlled Trial on Perioperative Pregabalin to Reduce Late-onset Complex Regional Pain Syndrome After Total Knee Arthroplasty

Conditions
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CRPS

Intervention / Treatment
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* Drug: pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of osteoarthritis Subjects who can understand and communicate in English. Exclusion Criteria: Younger than 21 years or older than 80 years. American Society of Anesthesiologists physical status IV. Prior usage of gabapentin (or pregabalin) will not be an exclusionary criterion; however, patients will have been withdrawn from these medications for at least 7 days before surgery. Patients with a history of neuropathic pain conditions. Patients who are currently enrolled in another investigational study. Pre-existing heart conditions Patients on thiazolidinedione class of anti-diabetic medications (eg. rosiglitazone, pioglitazone). -

Ages Eligible for Study
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Minimum Age: 21 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: 1 Placebo<br>Half of the patients will receive PO placebo for 14 days | Drug: Placebo<br>* Placebo for Given 2 hours prior to surgery, and twice a day for 14 postoperative days.<br>|
| Experimental: 2 Pregabalin<br>PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped. | Drug: pregabalin<br>* PO pregabalin 300 mg 2 hours prior to surgery, and 150 mg twice a day for 10 postoperative days. Pregabalin will be tapered to 75 mg twice daily between days 11 to 12 and then to 50 mg twice daily between days 13 to 14 post operatively and then stopped.<br>* Other names: Lyrica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epidural Medication Consumption Rate | Epidural medication consumption was recorded for each 4-h interval from the completion of surgery to the time that the epidural was discontinued (same as the time to achieve hospital discharge criteria). Because the discontinuation time varied from patient to patient (as they achieved physical therapy criteria), the average hourly consumption (total analgesic used divided by the total infusion time) was used as the measure of epidural drug use. | 36 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic Pain (S-LANSS > 12) | Patients will be evaluated in blinded fashion for lower extremity Complex Regional Pain Syndrome(CRPS) at pre-op, 1, 3, and 6 months postsurgery based initially on telephone interviews. An S-LANSS score of 12 or more was an indication of chronic neuropathic pain. Patients with an Self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs(S-LANSS) score of 12 or more at 6 mo came to the physician's office for a standardized physical examination, which included the S-LANSS examination items (allodynia and hyperalgesia) directly assessed by the physician, plus a pinprick evaluation. | 3 and 6 months post-surgery | 
| Knee Range of Motion (Active Flexion) |  | 1-30 days |