Efficacy of Perioperative Pregabalin in Reducing the Incidence of Chronic Neuropathic Pain and Postthoracotomy Syndrome.

This study is designed to assess:

1. The impact of taking perioperative pregabalin on the incidence of chronic neuropathic pain and postthoracotomy syndrome at 3 months in patients who have undergone a thoracotomy with a thoracic epidural as the basic analgesic modality.
2. The impact of taking perioperative pregabalin on the relief of acute pain, and on the use of additional analgesics, such as opioids, for the relief of such pain in patients who have undergone thoracic surgery with a thoracic epidural as the basic analgesia.
3. The impact of taking perioperative pregabalin on the quality of life and level of functioning of patients who underwent thoracic surgery 3 months earlier.
4. The safety profile of pregabalin in this patient population.

Hypothesis: The basic hypothesis in this study is that a dose of pregabalin administered preemptively 1 hour before a thoracotomy, then repeatedly during the postoperative period, when neuronal hyperexcitability is at a maximum (i.e., 4 days), will lead to a 33.3% decrease in the prevalence of chronic pain 3 months after surgery.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebo

Detailed Description

Postthoracotomy pain syndrome is a rather frequent phenomenon. Its incidence, as reported in the literature, varies but is around 52% at 1 to 2 years after surgery. This syndrome is defined as a persistent and/or recurrent pain or burning sensation along the thoracotomy scar at least 2 months after surgery. The pain is very significant, given that 3 to 5% of patients report it as being severe, and approximately 50% of patients report limitations in their activities of daily living secondary to this pain and consider their pain as their worst medical problem. A neuropathic component makes a certain contribution to this pain. Patients with this neuropathic component report more-severe pain and take more analgesics. Little is known about the origin of this pain, but it seems that the intensity of acute postoperative pain is the best predictor of it. Pregabalin could be a possible approach to reducing the prevalence of chronic postthoracotomy pain. Its efficacy has been demonstrated in several diabetic, postherpetic, incisional and inflammatory neuropathic pain models.

Methods:

One hundred and twenty patients will be divided in two equal groups (to receive pregabalin or placebo).

Prior to the induction of general anesthesia, a thoracic epidural will be placed and started immediately prior to surgery. The anesthetic technique and monitoring will be standardized.

During the immediate postoperative period, the intensity of pain will be assessed using a VNPS (0-10). Pain will be assessed upon the patient's arrival in and discharge from the recovery room and daily thereafter, for a total duration of four postoperative days or until discharge from hospital if this occurs before the 4th postoperative day.

Three months after their surgery, the patients will be contacted by telephone and administered a standardized questionnaire for evaluating:

• The presence and intensity (based on a VNPS) of pain at the surgical and/or drainage tube sites.
• The type of pain, with specific attention to identifying the presence of neuropathic pain.
• The patients' assessment of their quality of life, and the impact, if any, of the pain on their level of functioning in their daily lives in relation to their preoperative quality of life and functioning.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Centre Hospitalier de l'Université de Montréal (Hôpital Notre-Dame)

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 aged 18 to 80 years.
• Patients who are to undergo an elective thoracotomy in the lateral decubitus position.
• Patients who are ASA I to III inclusive.

Exclusion Criteria:

• A contraindication to pregabalin.
• A contraindication to the epidural technique.
• The current use of drugs belonging to the class of opioids, NMDA receptor blockers, membrane stabilizing agents (lidocaine mesylates, flecainide) or topical coanalgesics (capsaicin cream, lidocaine patch).
• Previous use of pregabalin or gabapentin.
• Preexisting pain at the site where the surgical incision will be made.
• Presence of a coexisting chronic pain syndrome.
• A creatinine clearance of less than 60 mL/min.
• A previous ipsilateral thoracotomy.
• A recent history of alcohol and/or drug abuse.
• A known allergy to local anesthetics or hydromorphone.
• The inability to understand a verbal numerical pain scale (VNPS) despite previous instruction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin; Study subjects will be randomized to receive on the morning of surgery, at least 30 minutes before induction, a 150 mg oral dose of pregabalin. Patients will then receive a 150 mg oral dose of pregabalin on the evening of the surgery. Subsequently, patients will receive a 150 mg oral dose of pregabalin twice daily on the following four postoperative days.	Drug: Pregabalin; 150 mg oral dose of pregabalin twice daily for 5 consecutive days.; Other Names: Lyrica
Placebo Comparator: Placebo; Study subjects will be randomized to receive a matching placebo on the morning of surgery, at least 30 minutes before induction. Patients will then receive a placebo on the evening of the surgery. Subsequently, patients will receive a placebo twice daily on the following four postoperative days.	Drug: Placebo; Matching oral placebo twice daily for 5 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of neuropathic pain and intensity of pain assessed using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale and Brief Pain Inventory questionnaire (BPI).	At 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Intensity of postoperative pain using a Visual Numeric Pain Scale (VNPS).	Day 1 to Day 4

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Investigators: Principal Investigator: François Girard, MD, Centre Hospitalier de l'Universite de Montreal (CHUM)

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: August 26, 2009
• First Submitted That Met QC Criteria: August 26, 2009
• First Posted (Estimate): August 27, 2009

Study Record Updates

• Last Update Posted (Estimate): April 12, 2012
• Last Update Submitted That Met QC Criteria: April 11, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Neuropathic pain; Thoracotomy
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; 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: PC 2010-001