Clinical trial NCT00819988: Pregabalin in the Prevention of Postoperative Delirium and Pain
Official title: A Randomized, Double-blind, Placebo-controlled Trial to Assess the Safety and Efficacy of the Perioperative Administration of Pregabalin in Reducing the Incidence of Postoperative Delirium and Improving Acute Postoperative Pain Management
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Delirium
Pain
Keywords: Postoperative
Perioperative
Orthopedic surgery
Vascular surgery
Gabapentinoid
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2009-01-09
Enrollment: 240
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether administration of pregabalin by mouth immediately preoperatively and three times daily for 3 days after surgery reduces the incidence of delirium postoperatively and improves overall pain control.

Detailed description: Delirium is a common postoperative complication occurring in up to 73% of patients sometime during their hospital stay. Elderly patients undergoing major surgical procedures are at highest risk. While many risk factors for delirium are known, the specific pathophysiology of postoperative delirium remains unclear and is likely multifactorial. The most common inciting agents and events include metabolic causes, medications, blood loss, hypoxemia and pain. Pain and its management are intimately related to the likelihood of developing postoperative delirium. As a class, gabapentinoids, such as pregabalin, have proven to reduce postoperative pain and narcotic consumption and therefore may have a role to play in the prevention of postoperative delirium.

Eligibility criteria: Inclusion Criteria:

* aged 60 years and older
* booked for major orthopaedic or vascular procedure
* expected length of stay \> 2 days

Exclusion Criteria:

* open AAA repair
* EVAR
* allergy/sensitivity to pregabalin or gabapentin
* use of pregabalin or gabapentin in previous 14 days
* severe liver disease
* severe renal dysfunction defined as either having creatinine clearance \< 30 ml/min or being dialysis-dependent
* seizure disorder
* MMSE \< 24/30
* inability to speak English or French

Primary outcomes:
measure: Delirium (patient is either CAM-ICU positive or positive for delirium by chart review)
timeFrame: postoperative day 1, 2, 3
Secondary outcomes:
measure: Interference with daily activities using BPI
timeFrame: postoperative day 3
measure: Pain at rest using NRS
timeFrame: postoperative days 1, 2, 3
measure: Pain with movement of the operative site using NRS
timeFrame: postoperative days 1, 2, 3
measure: Narcotic analgesic requirements
timeFrame: postoperative days 0, 1, 2, 3
measure: Sedation using RSS
timeFrame: postoperative days 1, 2, 3
measure: Narcotic-related adverse effects using ORSDS
timeFrame: postoperative days 1, 2, 3
measure: Recovery using the QoR
timeFrame: postoperative day 3
measure: Length of stay
timeFrame: Discharge day
measure: Medical Outcome Study (MOS) sleep score
timeFrame: Postoperative day 3
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: The Ottawa Hospital
name: Alan J Chaput, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: The Ottawa Hospital
name: Homer Yang, MD
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Gregory L Bryson, MD, MSc
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Holly Evans, MD
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Paul Beaule, MD
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Prasad Jetty, MD
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Barbara Power, MD
role: STUDY_DIRECTOR
References:
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citation: Bitsch M, Foss N, Kristensen B, Kehlet H. Pathogenesis of and management strategies for postoperative delirium after hip fracture: a review. Acta Orthop Scand. 2004 Aug;75(4):378-89. doi: 10.1080/00016470410001123.
citation: Morrison RS, Magaziner J, Gilbert M, Koval KJ, McLaughlin MA, Orosz G, Strauss E, Siu AL. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci. 2003 Jan;58(1):76-81. doi: 10.1093/gerona/58.1.m76.
citation: Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly. Best Pract Res Clin Anaesthesiol. 2003 Jun;17(2):259-72. doi: 10.1016/s1521-6896(03)00005-3.
citation: Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio ER. The impact of postoperative pain on the development of postoperative delirium. Anesth Analg. 1998 Apr;86(4):781-5. doi: 10.1097/00000539-199804000-00019.
citation: Gilron I. Review article: the role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective. Can J Anaesth. 2006 Jun;53(6):562-71. doi: 10.1007/BF03021846.
citation: Peng PW, Wijeysundera DN, Li CC. Use of gabapentin for perioperative pain control -- a meta-analysis. Pain Res Manag. 2007 Summer;12(2):85-92. doi: 10.1155/2007/840572.
citation: Leung JM, Sands LP, Rico M, Petersen KL, Rowbotham MC, Dahl JB, Ames C, Chou D, Weinstein P. Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients. Neurology. 2006 Oct 10;67(7):1251-3. doi: 10.1212/01.wnl.0000233831.87781.a9. Epub 2006 Aug 16.