Outcomes Of Perioperative Pregabalin On Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study aims to provide high quality evidence from a double-blinded, randomized controlled trial on the efficacy of perioperative pregabalin in reducing morphine requirements, improving pain scores and reducing chronic neuropathic pain when compared with placebo for primary total knee arthroplasty. It hence aims to improve on choice of analgesia adjuncts for total knee arthroplasty.

Detailed Description
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Aims: Whether pregabalin given preoperatively and for one week postoperatively in addition to patient-controlled analgesia (PCA) morphine is effective in reducing morphine requirements, improving pain scores and reducing chronic neuropathic pain when compared with placebo for primary total knee arthroplasty. Methodology: A single-centre double-blind randomized controlled trial in patients undergoing primary total knee arthroplasty. All subjects receive PCA morphine, paracetamol 1g every six hours, etoricoxib 120mg once daily postoperatively. Subjects receive either pregabalin 75mg po preoperatively followed by 75mg OM and 25mg ON for two days postoperatively or matching placebo. The primary outcome is cumulative morphine consumption at 72 hr following surgery. Secondary outcome measures included pain scores, knee range of motion and patient satisfaction.

Official Title
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Outcomes Of Perioperative Pregabalin On Total Knee Arthroplasty: A Randomized Controlled Trial

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: pregabalin
* Drug: Placebo
* Drug: Etoricoxib
* Drug: paracetamol
* Drug: Morphine
* Drug: Ropivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients undergoing primary total knee arthroplasty Exclusion Criteria: revision or bilateral arthroplasty, significant renal or hepatic impairment, documented allergy or intolerance to NSAIDs, paracetamol, morphine or pregabalin, chronic pain syndrome treated with chronic opioids, obstructive sleep apnea not treated with continuous positive airway pressure, seizures, breastfeeding, inability to use patient-controlled analgesia.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PREGABALIN<br>All subjects receive intravenous PCA morphine, paracetamol 1g po six hourly and etoricoxib 120mg po once daily. Subjects receive pregabalin 75mg orally preoperatively followed by 75mg at night for two days. During surgery, patients received general anaesthesia with femoral nerve block on the side of surgery. | Drug: pregabalin<br>* see arm/group description. Lyrica manufacture site: Pfizer Manufacturing Deutschland GmbH, Freiburg, Germany.<br>* Other names: Lyrica (Pfizer Pte Ltd, Singapore);Drug: Etoricoxib<br>* Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore<br>* Other names: 'Arcoxia';Drug: paracetamol<br>* Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia<br>* Other names: acetaminophen;Drug: Morphine<br>* patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany<br>Drug: Ropivacaine<br>* Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden<br>* Other names: 'Naropin';|
| Placebo Comparator: PLACEBO<br>All subjects receive intravenous PCA morphine, paracetamol 1g po six hourly and etoricoxib 120mg po once daily. Subjects receive either placebo tablet (of identical appearance to pregabalin) orally preoperatively followed by 75mg at night for two days. During surgery, patients received general anaesthesia with femoral nerve block on the side of surgery. | Drug: Placebo<br>* Placebo capsule containing lactose and MCC (no active ingredients).<br>* Other names: Manufactured by Beacons Pharmaceuticals Pte Ltd, Singapore.;Drug: Etoricoxib<br>* Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore<br>* Other names: 'Arcoxia';Drug: paracetamol<br>* Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia<br>* Other names: acetaminophen;Drug: Morphine<br>* patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany<br>Drug: Ropivacaine<br>* Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden<br>* Other names: 'Naropin';|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative morphine consumption at 72 hours postoperatively |  | 72 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional scores: SF-36v2 at 3 months and 6 months postoperatively |  | 3 months and 6 months postoperatively | 
| Functional scores: Knee Society Score at 3 months and 6 months postoperatively |  | 3 months and 6 months postoperatively | 
| Functional scores: WOMAC at 3 months and 6 months postoperatively | Western Ontario and McMaster Universities Arthritis Index (WOMAC) | 3 months and 6 months postoperatively | 
| Knee range of motion at 3 months and 6 months postoperatively |  | 3 months and 6 months postoperatively |