Pregabalin, Celecoxib, Total Knee Arthroplasty and Intrathecal Morphine (PCTKA)

Comparison of Analgesic Efficacy Among Pregabalin, Celecoxib, Pregabalin With Celecoxib and Placebo After Total Knee Arthroplasty Under Intrathecal Morphine

To evaluate whether pregabalin and/or celecoxib could improve analgesic efficacy of intrathecal morphine for patients after total knee arthroplasty.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty; Postoperative Pain Management
• Intervention / Treatment: Drug: Pregabalin; Drug: Celecoxib; Drug: Pregabalin with celecoxib; Drug: Placebo

Detailed Description

A single-dose spinal anesthesia combining with morphine for total knee arthroplasty (TKA) is a simple, economical anesthetic technique commonly used in our hospital. Still some patients could not get effective postoperative pain control. Pregabalin, an anticonvulsant, has been shown to reduce acute pain after molar extraction, laparoscopic cholecystectomy, and reduce postoperative morphine requirement after total hip arthroplasty, and celecoxib, a selective cyclo-oxygenase (COX) - 2 inhibitor, with perioperative prescription is successfully reduces pain score and opioid consumption after TKA under spinal anesthesia alone. However, no clinical study has yet investigated whether preoperative single-dose of pregabalin, celecoxib or in combination compared to placebo can improve analgesic efficacy of intrathecal morphine after TKA. The primary objective of this study was to evaluate whether these medications could reduce pain scores at rest / when movement and morphine requirement after TKA under spinal anesthesia with intrathecal morphine. Secondary outcome assessed include adverse effects, anxiety score and patients' satisfaction score.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Supranee Niruthisard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients between 50-75 years of age
• Patients with an American Society of Anesthesiologists physical status of I to III
• Patients scheduled for primary TKA with a diagnosis of osteoarthritis under spinal anesthesia

Exclusion Criteria:.

• Patients had a known allergy to any of the medications being used
• a history of drug or alcohol abuse
• a history of taking chronic pain medications (ie, show-release preparations of opioids, given that morphine consumption was the primary outcome)
• a history of taking pregabalin or gabapentin / non-steroidal anti-inflammatory drugs / COX-2 inhibitors
• a psychiatric disorder
• a history of impaired renal function (Cr > 1.5 mg/dl), peptic ulcer, asthma, thrombotic cerebrocardiovascular diseases, uncontrolled hypertension
• a history of contraindication for spinal anesthesia
• a history of bleeding tendency
• pregnancy
• unable or unwilling to use patient - controlled analgesic (PCA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pregabalin; Oral single-dose of pregabalin (150 mg) and 1 capsule of placebo (P) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.	Drug: Pregabalin; Oral single-dose of pregabalin (150 mg) and placebo (P) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.; Other Names: Pregabalin: Lyrica
Active Comparator: Celecoxib; Oral single-dose of celecoxib (400 mg) and 1 capsule of placebo (C) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.	Drug: Celecoxib; Oral single-dose of celecoxib (400 mg) and placebo(C)1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.; Other Names: Celecoxib: Celebrex
Active Comparator: Pregabalin with celecoxib; Oral single-dose of pregabalin (150 mg) and celecoxib (400 mg) (PC) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.	Drug: Pregabalin with celecoxib; Oral single-dose of pregabalin (150 mg) and celecoxib (400 mg) (PC) 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg.; Other Names: Pregabalin: Lyrica; Celecoxib: Celebrex
Placebo Comparator: Placebo; Oral single-dose of placebo 2 capsules 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg	Drug: Placebo; Oral single dose of placebo 2 capsules 1-2 hours before starting spinal anesthesia with intrathecal morphine 0.2 mg; Other Names: Placebo: sugar capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour cumulative morphine consumption	The time to first morphine requirement will be recorded; The cumulative morphine consumption will be recorded at the end of surgery and 2-h, 6-h, 10-h, 24-h, and 48-h postoperatively; Visual analog scale (VAS) pain scores at rest will be assessed at the night before surgical date, before starting anesthesia, at the end of surgery, and 2-h, 6-h, 10-h, 24-h and 48-h postoperatively; Visual analog scale (VAS) pain scores when on movement will be assessed at the end of surgery, and 2-h, 6-h, 10-h, 24-h and 48-h postoperatively	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety scores (VAS), patients' satisfaction	Anxiety scores will be assessed at the night before surgical date, before starting anesthesia, at the end of surgery, and 2-h, 6-h, 10-h, 24-h and 48-h postoperatively;; 24-h and 48-h patients' satisfaction (0-10,0=dissatisfied and 10= very satisfied)	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Collaborators: King Chulalongkorn Memorial Hospital; Bhumibol Adulyadej Hospital
• Investigators: Principal Investigator: Supranee Niruthisard, BSc, MD, King Chulalongkorn Memorial Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: April 26, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (Estimate): April 29, 2011

Study Record Updates

• Last Update Posted (Estimate): August 4, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Celecoxib; Total knee arthroplasty; Intrathecal morphine; Pregabalin
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Cyclooxygenase 2 Inhibitors; Calcium Channel Blockers; Celecoxib; Pregabalin
• Other Study ID Numbers: anesTKA08