Pregabalin, Celecoxib, Total Knee Arthroplasty and Intrathecal Morphine

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

Detailed Description
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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.

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

Conditions
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Postoperative Pain Management, Total Knee Arthroplasty

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Celecoxib
* Drug: Pregabalin with celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregabalin, Celecoxib, Intrathecal morphine, Total knee arthroplasty