Pregabalin and Post-thoracotomy Pain

Study Overview
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Brief Summary
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With Institutional Ethics Board approval and signed informed consent, a pilot investigation was conducted in which 15 adult patients scheduled to undergo a thoractomy were randomly assigned to receive 1) 150 mg pregabalin 1 hour preoperatively and then 7 days postoperatively (BID) or 2) 300 mg pregabalin 1 hour preoperatively and 7 days postoperatively (BID) or 3) placebo for same regimen to assess the feasibility, safety and compliance of this drug regimen on this patient population. This assessment was necessary in order to plan a future fully powered randomized controlled trial looking at the efficacy of perioperative pregabalin ifor reducing the incidence/severity of chronic post-thoracotomy pain.

Detailed Description
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Chronic post thoracotomy pain syndrome (CPTPS) is a significant problem that has important effects on patients' daily activities. The severity of postoperative pain and the central sensitization associated with it are thought to play a role in the chronification of acute pain. Gabapentin has been shown to be effective in reducing acute post-surgical pain and treating CPTPS. There is conflicting data regarding its effects on the development of chronic post-surgical pain. Although pregabalin is similar to gabapentin there are only a few studies examining its use in the modification of post-surgical pain but evidence suggests that it might be effective. There are no studies examining the effect of pregabalin on the development of chronic post-surgical pain. Our hypothesis is that perioperative use of pregabalin will decrease the incidence of CPTPS. Our ultimate goal is to conduct a multi-center study assessing the effect of perioperative oral pregabalin on the development of CPTPS. Prior to this, we will carry out a prospective, randomized, placebo controlled, double-blinded pilot study to assess the feasibility, safety, and compliance associated with perioperative use of oral pregabalin in patients undergoing video assisted thoracotomy surgery (VATS) or open thoracotomy procedures.

Official Title
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A Prospective, Randomized, Double Blinded, Placebo Controlled Pilot Study Assessing the Effect of Perioperative Pregabalin on the Incidence of Chronic Post Thoracotomy Pain Syndrome

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective thoracotomy (ET) or video assisted thoracotomy (VAT); Understanding and provision of written informed consent; Age > 18 and < 75; ASA class I, II or III. Exclusion Criteria: Inability to adhere to study protocol; Intolerance or known hypersensitivity to any agents to be used in the study; Contraindication to thoracic epidural placement in open thoracotomy patients; Inability to respond to the study questionnaire; Renal insufficiency (serum creatinine > 1.5 x upper limit of normal); BMI > 40; Confounding procedural factors which might affect validity of data; Surgery for tumour extending into the chest wall; Requirement for second thoracotomy or re-occurrence of disease after surgery; Potential interaction with study medications and patient's current medications; Current ETOH or substance abuse; Pre-existing chronic pain requiring chronic analgesic use; History of seizure disorder requiring treatment with an anti-convulsant; Current therapy with thiazolidinedione class oral hypoglycemic agents (e.g. Actos, Avandia, or Avandamet); History of congestive heart failure; Major psychiatric disorder; Insufficient safety data in a specific patient population; Pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Perioperative pregabalin<br>Pregabalin 150mg administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-operatively (n=3) or Pregabalin 300mg administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-operatively (n=4). | Drug: Pregabalin<br>* PHASE 1 (N=3) Pregabalin 150mg administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-op. PHASE 2 (N=4) Pregabalin 300mg administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-op.<br>|
| Placebo Comparator: Placebo control<br>An identical placebo administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-op. (N=8) | Drug: Placebo<br>* An identical placebo administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-op (N=8)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome Measure for the Final Study Will be the Incidence of CPTPS at 2 Months. |  | 2, 4, and 6 months | 
| Incidence of Chronic Post-thoracotomy Pain at 2 Months Postoperatively | Incidence of post-thoracotomy pain syndrome (persistent continuous or intermittent chest pain with resting pain score > 4 on a 10 point NRS scale) | 2 months postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thoracotomy, Post-surgical, Pregabalin