Pain Treatment With Combinations of NSAIDs

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain, Acute
• Intervention / Treatment: Drug: Celecoxib; Drug: Aspirin; Drug: Ketorolac

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Chuvashia
    • Cheboksary, Chuvashia, Russian Federation, 429500
      • Federal Center for Traumatology, Orthopedics and Endoprosthetics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Drug: celecoxib; 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; The patients received celecoxib in a dose of 400 mg orally daily.
Experimental: Drug: aspirin with ketorolac; 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; The patients received aspirin in a dose of 100 mg orally daily.; Drug: Ketorolac; The patients received ketorolac in a dose of 90 mg mg orally daily.
Experimental: Drug: ketorolac and celecoxib; 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: Celecoxib; The patients received celecoxib in a dose of 400 mg orally daily.; Drug: Ketorolac; The patients received ketorolac in a dose of 90 mg mg orally daily.
Active Comparator: Drug: aspirin, ketorolac and celecoxib; 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: Celecoxib; The patients received celecoxib in a dose of 400 mg orally daily.; Drug: Aspirin; The patients received aspirin in a dose of 100 mg orally daily.; Drug: Ketorolac; The patients received ketorolac in a dose of 90 mg mg orally daily.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federal State Budgetary Organization, Federal Center for Traumatology, Orthopedics and Arthroplasty
• Investigators: Principal Investigator: Vladimir U. Emelianov, MD PhD, Federal Center for Traumatology, Orthopedics and Arthroplasty, Cheboksary, Russia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 16, 2023

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Aspirin; Celecoxib; Postoperative pain; Ketorolac; Non-steroidal anti-inflammatory drugs; Combination of NSAID
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Acute Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Cyclooxygenase 2 Inhibitors; Aspirin; Ketorolac; Celecoxib
• Other Study ID Numbers: 2021-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No