Chronic Pain
Conditions
Keywords
Thoracotomy, Post-surgical, Pregabalin
Brief summary
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
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.
Interventions
DRUGPregabalin
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.
DRUGPlacebo
An identical placebo administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-op (N=8)
Sponsors
Queen's University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) |
Countries
Canada
Participant flow
Recruitment details
REB approval from our institution was received to enroll 15 patients, who had given written informed consent, into this pilot study. All elective ASA I - III patients aged 18 - 75 scheduled for open thoracotomy or video assisted thoracotomy (VAT) were screened for inclusion in this study.
Pre-assignment details
Thirty-nine patients were screened between April 23 and November 27, 2008. Fifteen patients were eligible for inclusion.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin 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. | 7 |
| Placebo An identical placebo administered one hour prior to surgery and 12 hours after surgery, then continued BID until day 7 post-op. (N=8) | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | somnolence | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Pregabalin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Continuous | 55.0 years STANDARD_DEVIATION 18.6 | 60.6 years STANDARD_DEVIATION 17.6 | 57.6 years STANDARD_DEVIATION 17.7 |
| Region of Enrollment Canada | 8 participants | 7 participants | 15 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 7 | 0 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 |
Outcome results
Primary
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)
Time frame: 2 months postoperatively
Population: pilot study--convenience
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Incidence of Chronic Post-thoracotomy Pain at 2 Months Postoperatively | 0 participants |
| Placebo | Incidence of Chronic Post-thoracotomy Pain at 2 Months Postoperatively | 0 participants |
Primary
The Primary Outcome Measure for the Final Study Will be the Incidence of CPTPS at 2 Months.
Time frame: 2, 4, and 6 months