Pain Treatment With Combinations of NSAIDs

Study Overview
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Brief Summary
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The search for new safe and effective methods of pain relief after surgery on large joints is still an urgent problem. The most optimal approach in the treatment of postoperative pain is the use of multimodal analgesia with a different mechanism of action that act on various mechanisms of pain and can include opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, anticonvulsants, NMDA antagonists, alpha-2-agonists, and sodium and calcium channel blocking agents, as well as local anesthetics. NSAIDs are the most popular and safe means for pain relief. Therefore, a lot of efforts are aimed at increasing the effectiveness of NSAIDs use. The aim of this study was to evaluate the effectiveness of simultaneously administering two or three NSAIDs, compared to using only one NSAID, for pain relief after surgery on large joints such as hip or knee arthroplasty.

Detailed Description
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This is 6 days, randomized, double blind, parallel group, single-center study in 105 subjects. The distribution into groups was carried out by sequentially alternating the set into 4 groups celecoxib 400 mg orally daily, aspirin 100 mg and ketorolac 90 mg orally daily, ketorolac 90 mg and celecoxib 400 mg orally daily; aspirin 200 mg, ketorolac 90 mg and celecoxib 400 mg orally daily.

Official Title
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Pain Treatment After Joint Surgery With a Combination of Aspirin, Ketorolac, and Celecoxib.

Conditions
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Postoperative Pain, Acute

Intervention / Treatment
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* Drug: Aspirin
* Drug: Ketorolac
* Drug: Celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients with diagnosis of osteoarthritis of the knee or hip joint (M15.0, M16, M17) after primary knee or hip arthroplasty. Informed consent. Exclusion Criteria: Patients who cannot cooperate with the trial. Pregnant or breast feeding women, Оpioid addiction, Contraindication to NSAIDs (allergy to NSAID, history of ulcer and gastrointestinal bleeding, liver failure, renal failure (eGRF < 60 ml/kg/1,73m2) and chronic kidney disease 2-5, known thrombocytopenia (<100 mia/L)

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drug: celecoxib<br>The patients received celecoxib in a dose of 400 mg orally daily. The drug was prescribed from the second day of the operation for 5 days. | Drug: Celecoxib<br>* The patients received celecoxib in a dose of 400 mg orally daily.<br>|
| Experimental: Drug: aspirin with ketorolac<br>The patients received aspirin in a dose of 100 mg and ketorolac 90 mg orally daily. The drugs were prescribed from the second day of the operation for 5 days. | Drug: Aspirin<br>* The patients received aspirin in a dose of 100 mg orally daily.<br>Drug: Ketorolac<br>* The patients received ketorolac in a dose of 90 mg mg orally daily.<br>|
| Experimental: Drug: ketorolac and celecoxib<br>The patients received ketorolac in a dose of 90 mg and celecoxib 400 mg orally daily. The drugs were prescribed from the second day of the operation for 5 days. | Drug: Ketorolac<br>* The patients received ketorolac in a dose of 90 mg mg orally daily.<br>Drug: Celecoxib<br>* The patients received celecoxib in a dose of 400 mg orally daily.<br>|
| Active Comparator: Drug: aspirin, ketorolac and celecoxib<br>The patients received aspirin in a dose of 200 mg, ketorolac 90 mg, and celecoxib 400 mg orally daily. The drugs were prescribed from the second day of the operation for 5 days. | Drug: Aspirin<br>* The patients received aspirin in a dose of 100 mg orally daily.<br>Drug: Ketorolac<br>* The patients received ketorolac in a dose of 90 mg mg orally daily.<br>Drug: Celecoxib<br>* The patients received celecoxib in a dose of 400 mg orally daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measuring postoperative pain using the visual analog scale for pain (VAS-P) | The patients choose the score on the 10 cm line scale with (VAS-P) rage from 0 ('no pain') to 10 (severe pain). | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arachidonic acid-stimulated platelet tests | Assessed by Multiplate ASPItest, Roche Diagnostics GmbH. The platelet aggregation expressed in arbitrary aggregation units (AU) multiplied by the recorded time in minutes (AU*min). | 5 days | 
| Hemoglobin | Hemoglobin (HGB) level in g/L | 5 days | 
| Hematocrit | Hematocrit level in % | 5 days | 
| Erythrocytes | Erythrocytes (RBC) number in 1 litter | 5 days | 
| Platelets cells | Platelets cells (PLT) number in 1 litter | 5 days | 
| Fibrinogen | Fibrinogen level in g/L | 5 days | 
| Partial thromboplastin time | Partial thromboplastin time (PTT) in seconds | 5 days | 
| Prothrombin time | Prothrombin time in % | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-steroidal anti-inflammatory drugs, Postoperative pain, Combination of NSAID, Aspirin, Ketorolac, Celecoxib