Outcomes Of Perioperative Pregabalin On Total Knee Arthroplasty

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

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.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: pregabalin; Drug: Etoricoxib; Drug: paracetamol; Drug: Morphine; Drug: Ropivacaine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PREGABALIN; 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; see arm/group description. Lyrica manufacture site: Pfizer Manufacturing Deutschland GmbH, Freiburg, Germany.; Other Names: Lyrica (Pfizer Pte Ltd, Singapore); Drug: Etoricoxib; Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore; Other Names: 'Arcoxia'; Drug: paracetamol; Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia; Other Names: acetaminophen; Drug: Morphine; patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany; Drug: Ropivacaine; Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden; Other Names: 'Naropin'
Placebo Comparator: PLACEBO; 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: Etoricoxib; Etoricoxib 120mg per oral once daily on postoperative days 1,2,3. 'Arcoxia' manufacture site: MSD International GMBH, Singapore; Other Names: 'Arcoxia'; Drug: paracetamol; Paracetamol 1g per oral 6hourly on postoperative days 1,2,3. Manufacture site: SM Pharmaceuticals, Malaysia; Other Names: acetaminophen; Drug: Morphine; patient-controlled analgesia intravenous morphine sulphate on postoperative days 1,2,3. Manufacture site: Hameln Pharma Plus GMBH, Hameln, Germany; Drug: Ropivacaine; Femoral block with ropivacaine 0.5% 30mls. Ropivacaine manufacture site: AstraZeneva AB, Sweden; Other Names: 'Naropin'; Drug: Placebo; Placebo capsule containing lactose and MCC (no active ingredients).; Other Names: Manufactured by Beacons Pharmaceuticals Pte Ltd, Singapore.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: lingaraj krishna, frcs (Orth), National University Health System, Singapore

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: October 1, 2016

More Information

Terms related to this study

• 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; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Anesthetics, Local; Calcium-Regulating Hormones and Agents; Cyclooxygenase 2 Inhibitors; Calcium Channel Blockers; Acetaminophen; Pregabalin; Ropivacaine; Morphine; Etoricoxib
• Other Study ID Numbers: 190514

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No