Analgesic Effect of Gabapentin in Total Knee Arthroplasty (TKA)

Analgesic Effect of Perioperative Gabapentin in Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled, Dose-response Study

Pain is a major problem after TKA. Gabapentin may reduce acute postoperative pain. The investigators therefore investigate the effect of Gabapentin as a perioperative analgesic.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Postoperative Sedation
• Intervention / Treatment: Drug: Gabapentin; Drug: Gabapentin; Drug: Placebo

Detailed Description

Pain is a major problem after TKA. Studies indicate that Gabapentin may reduce acute postoperative pain. However, the optimal dose is unknown and there is constant controversy on analgesic versus side-effects. The investigators therefore investigate the effect of Gabapentin as a perioperative analgesic in a dose-related manner and with a sample-size allowing evaluation of side-effects.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Dep. of ortopedic surgery, Aalborg Sygehus
  • Esbjerg, Denmark, 6700
    • Dep. of ortopedic surgery, Esbjerg Sygehus
  • Hvidovre
    • Copenhagen, Hvidovre, Denmark
      • Dep. of anesthesiology and ortopedic surgery Hvidovre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary, unilateral total knee arthroplasty (TKA)
• Age 50-85 years
• Ethnic Danes

Exclusion Criteria:

• Treatment with gabapentins, systemic glucocorticoids, opioids, anxiolytic agents, antiepileptics or antidepressive agents (last 4 weeks)
• History of depression or mania
• History of alcohol or drug abuse
• History of malignancy
• History of epilepsia
• BMI > 40
• Disease affecting central or peripheral nerve function
• History of dementia
• History of renal insufficiency
• Allergy to Gabapentin
• Women with menstruation (last 2 years)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gabapentin "high"; Tables with Gabapentin (1300 mg/day) for 7 days, starting on the day of surgery	Drug: Gabapentin; Tables with Gabapentin (1300 mg/ day) for 7 days, starting on the day of surgery; Drug: Gabapentin; Tables with Gabapentin (900 mg/day) for 7 days, starting on the day of surgery
Active Comparator: Gabapentin "intermediate"; Tables with Gabapentin for 7 days (900 mg/day), starting on the day of surgery	Drug: Gabapentin; Tables with Gabapentin (1300 mg/ day) for 7 days, starting on the day of surgery; Drug: Gabapentin; Tables with Gabapentin (900 mg/day) for 7 days, starting on the day of surgery
Placebo Comparator: Placebo; Placebo tablets for 7 days, starting on the day of surgery	Drug: Placebo; Placebo tablets for 7 days, starting on the day of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain	Pain during walking at 24 hour after surgery, visuel analog scale (VAS, 0-100 mm)	At 24 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation	Sedation at 6 hours, numeric range scale (NRS, 0-10)	At 6 hours
Pain	Pain at rest and during walking the first week after TKA, visuel analog scale (VAS, 0-100 mm)	1 week
Cumulated pain scores	Cumulated pain scores for pain the first week after TKA	1 week
Amount of rescue analgesic	Amount of rescue analgesic the first week after TKA, mg	1 week
Side effects	Side effects the first week after TKA	1 week
Cumulated side effects scores	Cumulated side effects scores the first week after TKA	1 week
Amount of ondansetron and sleeping medicine	Amount of ondansetron and sleeping medicine the first week after TKA, mg	1 week
Anxiety and depression	Anxiety and depression - questionnaire - the first week after TKA, Hospitality and Anxiety and Depression Scale	1 week
Gabapentin level in blood-sample	Gabapentin level in blood-sample at 12 am on the first day after surgery, serum-koncentration	1 Day

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Lundbeck Foundation
• Investigators: Principal Investigator: Torben B Hansen B Hansen, MD, Regionshospitalet Holstebro; Study Director: Henrik Kehlet, MD, Rigshospitalet, Denmark; Principal Investigator: Jørgen B Dahl, MD, Rigshospitalet, Denmark; Principal Investigator: Per W Kristensen, MD, Vejle Sygehus; Principal Investigator: Henrik Husted, MD, Hvidovre University Hospital; Principal Investigator: Søren Solgaard, MD, Gentofte Hospital; Principal Investigator: Mogens B Laursen, MD, Phd., Aalborg Sygehus; Principal Investigator: Lars Hansen, MD, Esbjerg Sygehus

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: January 6, 2012
• First Submitted That Met QC Criteria: January 6, 2012
• First Posted (Estimate): January 10, 2012

Study Record Updates

• Last Update Posted (Estimate): April 11, 2014
• Last Update Submitted That Met QC Criteria: April 10, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: THL-06-11; 2011-003105-22 (EudraCT Number); H-4-2011-082 (Registry Identifier: Ethics Committee)