Parecoxib in Total Knee Arthroplasty

Study Overview
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Brief Summary
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Early mobilization and rehabilitation can be difficult after total knee arthroplasty (TKA) due to a high incidence of moderate to severe postoperative pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are important to multimodal analgesic protocols. Parecoxib is an NSAID that selectively inhibits the enzyme cyclooxygenase-2 (COX-2). Clinical trials have shown that it does not alter platelet function or gastric mucosa. A recent study, after comparing ketorolac and parecoxib used at the same time in infiltration and systemically, found no differences in perioperative analgesia with a tendency to less bleeding in the parecoxib group. This randomized study will compare the effectiveness of adding a COX-2 inhibitor in the pain management of patients undergoing TKA as part of a multimodal analgesia regimen. The morphine consumption was selected as the primary outcome. The study hypothesis is that patients receiving parecoxib would have a lower opioid consumption.

Official Title
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A Randomized Comparison Between Parecoxib and Placebo Added to a Standard Perioperative Analgesic Protocol for Total Knee Arthroplasty

Conditions
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Pain, Postoperative, Pain, Acute, Analgesia, Analgesic Nephropathy, Analgesic Adverse Reaction, Knee Osteoarthritis

Intervention / Treatment
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* Drug: Intravenous study drug
* Other: Intravenous saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA I - III BMI 20 - 35 (kg/m2) Exclusion Criteria: Adults who are not capable of giving their own consent Pre-existing neuropathy (assessed in the history and physical examination) Coagulation disturbance (assessed on history and physical examination, if clinically necessary, by blood test, i.e. platelets ≤ 100,000, international normalized ratio ≥ 1.4 or prothrombin time ≥ 50) Renal failure (assessed by history and physical examination, if considered clinically necessary, by blood test, i.e. creatinine ≥ 1.04 mg/dl) Hepatic impairment (assessed by history and physical examination, if considered clinically necessary, by blood tests, i.e. transaminases (GGT ≥ 50 u/lt) Allergy to local anesthetics, morphine, paracetamol, ketorolac or parecoxib Pregnancy Chronic pain syndromes that require the use of opioids at home Known history of sulfa allergy History of ischemic heart disease History of chronic gastritis or peptic ulcer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parecoxib<br>This arm will receive intravenous parecoxib in the intraoperative period. | Drug: Intravenous study drug<br>* 40mg parecoxib will be administered intravenously after general anesthesia induction and before tourniquet inflation and surgical incisión<br>|
| Placebo Comparator: Placebo<br>This arm will receive a placebo intravenous injection containing saline solution in the same volume as the intervention group | Other: Intravenous saline solution<br>* Saline solution (same volume as the study drug) will be administered intravenously after general anesthesia induction and before tourniquet inflation and surgical incision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine consumption | Morphine consumed postoperatively during the first 24 hrs utilizing a patient-controlled analgesia device programmed 1mg/ml morphine solution, no infusion, 1ml dose, 8 minutes lockout. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basal quadriceps strength in the operative side | Leg extension strength measured with a handheld dynamometer | 1 hour before surgery | 
| Basal level of pain during leg extension in the operative side | Pain level measured with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 1 hour before surgery | 
| Basal plasmatic creatinine | Plasmatic creatinine level measured in mg/dL from a blood sample | 1 hour before surgery | 
| Nerve block performance time | Time elapsed between skin disinfection and the end of local anesthetic injection in femoral triangle and posterior capsule blocks. | 5 minutes after anesthesia induction (before surgical incision) | 
| Incidence of Block complications | Report of vascular puncture, hematoma, local anesthetic systemic toxicity symptoms | 5 minutes after anesthesia induction and before surgical incision | 
| Time to first morphine dose request | Time in minutes between arrival to post anesthesia care unit arrival and first request of morphine with the patient controlled analgesia device | 24 hours | 
| Morphine consumption during first 48 hours | Morphine consumed postoperatively during the first 48 hrs utilizing a patient-controlled analgesia device programmed 0.01mg/Kg/ml morphine solution, no infusion, 1ml dose, 8 minutes lockout. | 48 hours | 
| Incidence of opioid related side effects | Report of nausea, vomitus, pruritus, urinary retention, respiratory depression | 48 hours | 
| Incidence of NSAIDs related clinical side effects | Report of allergic reactions, pyrosis, evident gastrointestinal bleeding, hematoma | 48 hours | 
| Postoperative static pain level at 3 hours | Pain level measured at rest with an 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 3 hours | 
| Postoperative dynamic pain level at 3 hours | Pain level measured during leg extension with an 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 3 hours | 
| Postoperative static pain level at 6 hours | Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 6 hours | 
| Postoperative dynamic pain level at 6 hours | Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 6 hours | 
| Postoperative static pain level at 12 hours | Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 12 hours | 
| Postoperative dynamic pain level at 12 hours | Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 12 hours | 
| Postoperative static pain level at 24 hours | Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 24 hours | 
| Postoperative dynamic pain level at 24 hours | Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 24 hours | 
| Postoperative static pain level at 48 hours | Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 48 hours | 
| Postoperative dynamic pain level at 48 hours | Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain) | 48 hours | 
| Medial malleolus sensory block level | 0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch | 3 hours | 
| Lateral malleolus sensory block level | 0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch | 3hours | 
| Medial malleolus sensory block level | 0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch | 24 hours | 
| Lateral malleolus sensory block level | 0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch | 24 hours | 
| Postoperative quadriceps strength | Leg extension strength measured with a handheld dynamometer | 3 hours | 
| Postoperative quadriceps strength | Leg extension strength measured with a handheld dynamometer | 24 hours | 
| Incidence of restriction to perform physiotherapy | Inability to perform physiotherapy secondary to pain or motor blockade | 6 hours | 
| Incidence of restriction to perform physiotherapy | Inability to perform physiotherapy secondary to pain or motor blockade | 24 hours | 
| Incidence of restriction to perform physiotherapy | Inability to perform physiotherapy secondary to pain or motor blockade | 48 hours | 
| Postoperative plasmatic creatinine level | Plasmatic creatinine level measured in mg/dL from a blood sample | 48 hours |