Depot-opioids for Pre- and Postoperative Pain Relief After Primary Knee Arthroplasty.Tapentadol vs Oxycodone vs Placebo

Study Overview
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Brief Summary
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This study will provide knowledge about the use of long-acting opioids for pain relief after primary knee arthroplasty. The investigators will compare depot tapentadol, depot oxycodone and placebo for effect on pain relief and side effects. The three study groups reflect the three different postoperative pain regimens that have been used the last years at St. Olavs Hospital, so investigators know that no patient will receive an inadequate pain treatment. The purpose of the study is to find which of the three treatments that gives the best pain relief with the least amount of side effects. The results will be of use for postoperative pain treatment for knee arthroplasty, but also for other types of major surgery. Similar studies that are not sponsored by pharmaceutical industry have not been published yet.

Official Title
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Depot-opioids for Pre- and Postoperative Pain Relief After Primary Knee Arthroplasty. A Double Blinded Randomized Controlled Study. Tapentadol vs Oxycodone vs Placebo

Conditions
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Joint Diseases

Intervention / Treatment
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* Drug: Tapentadol
* Drug: Oxycodone
* Drug: Placebo
* Drug: usual pain treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: scheduled for knee arthroplasty at St. Olavs University Hospital consent in participation in the study Exclusion Criteria: Contraindications for any of the study drugs Lactose intolerance Known hypersensitivity against any of the additives Chronic Obstructive Pulmonary Disease (COPD) grade 3 or 4 Paralytic ileus Known alcohol or medical addiction/abuse History of asthma, urticaria or allergic reaction caused by acetyl salicylic acid or other NSAIDs Peptic ulcer Hemophilia Gastrointestinal bleeding Cerebrovascular bleeding Inflammatory bowel disease (ulcerous colitis, Crohn disease) Concomitant use of the following drugs: ACE-inhibitors, AT2-blockers, SSRI, Anti-psychotic drugs, MAO-inhibitors, Atazanavir and Nelfinavir (medicine used for HIV-infection) Known kidney failure (creatinin level above reference value) Known heart failure (NYHA III-IV) Pregnancy Women in fertile age with risk of pregnancy Nursing women operated under general anesthesia without use of spinal anesthesia using opioids on a regular basis except users of codeine or tramadol, or known former abuse of opioids Cognitive failure or other factors which make follow up impossible (for example language difficulties) No cell phone or internet connection at home (making follow up difficult)

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapentadol<br>depot Tapentadol in addition to usual pain treatment | Drug: Tapentadol<br> <br> * Other names: Palexia Depot;Drug: usual pain treatment<br>* premedication of Dexamethasone, Paracetamol, Vimovo; postoperative Paracetamol and Vimovo<br>|
| Active Comparator: Oxycodone<br>depot Oxycodone in addition to usual pain treatment | Drug: Oxycodone<br> <br> * Other names: Oxycontin;Drug: usual pain treatment<br>* premedication of Dexamethasone, Paracetamol, Vimovo; postoperative Paracetamol and Vimovo<br>|
| Placebo Comparator: Placebo<br>depot glucose placebo in addition to usual pain treatment. | Drug: Placebo<br> <br> * Other names: Glucose;Drug: usual pain treatment<br>* premedication of Dexamethasone, Paracetamol, Vimovo; postoperative Paracetamol and Vimovo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under curve (AUC) based on daily numeric rating score (NRS) scale 1-10 for pain by mobilization the first 8 postoperative days | NRS-scores | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain at rest in the previous 24 hours | NRS-scores 1-10 scale | 8 days | 
| worst pain in the previous 24 hours | NRS-scores 1-10 scale | 8 days | 
| quality of sleep in the previous night | NRS-scores 1-10 scale | 8 days | 
| nausea in the previous 24 hours | NRS-scores 1-10 scale | 8 days | 
| obstipation in the previous 24 hours | NRS-scores 1-10 scale | 8 days | 
| dizziness in the previous 24 hours | NRS-scores 1-10 scale | 8 days | 
| sedation in the previous 24 hours | NRS-scores 1-10 scale | 8 days | 
| headache | NRS-scores 1-10 scale | 8 days in the previous 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthroplasty, Replacement, Knee, Analgesics, Knee, Administration and dosage, Postoperational care, Pain management