A Study to Compare Different Ways of Steroid Administration After Total Knee Implantation

Comparison of Perioperative Intravenous vs Periarticular Dexamethasone vs no Steroid Supplementation in Terms of Post-operative Pain, Function, Nausea, Hospitalization Length, and Risk of Complications in Patients Undergoing Primary Total Knee Arthroplasty for Knee Osteoarthritis - A Randomized Controlled Trial Clinical Study Protocol

We are going to evaluate the difference between perioperative intravenous steroid supplementation, perioperative periarticular steroid supplementation, and standard anaesthesia protocols. We'll evaluate the outcome of patients with knee osteoarthritis who are undergoing Total Knee Arthroplasty to understand which of the three treatments give more benefits to the patient.

Study Overview

• Status: Recruiting
• Conditions: Total Knee Replacement
• Intervention / Treatment: Drug: Dexamethasone Sodium Phosphate 4 mg/ml intravenous; Drug: Dexamethasone Sodium Phosphate 4 mg/ml intra-articular

Detailed Description

A total of 159 patients will be needed (53 patients per arm, 3 arms in total). Dexamethasone (brand name: Mephameson) is the steroid drug that we perioperative administer in two different ways: intra-venous (IV) dexamethasone (9mg) in arm-A, intra-articular (IA) dexamethasone (9mg) in arm-B. No steroid supplementation will be provided in the control group (arm-C).

The primary objective of the study is to compare the effect on post-operative pain of I.V. and I.A. perioperative dexamethasone supplementation for total knee arthroplasty (TKA).

The secondary objectives of the studies will be the comparison between I.V. and I.A. peri-operative dexamethasone supplementation in terms of post-operative pain and function, opioids and analgesic drugs consumption, knee range of motion, systemic inflammatory response, time to mobilisation, length of stay, and patient satisfaction.

Moreover, both I.V. and I.A. steroid supplementation protocols will be compared to routine analgesia protocol (no steroid supplementation group) in order to document their advantages over the absence of steroid supplementation.

The safety of I.V. and I.A. peri-operative dexamethasone will be evaluated and compared recording all the steroid supplementation related complications. In particular, the risk of hyperglycaemia-related complications and post-operative infections will be documented. The safety of both I.V. and I.A. steroid supplementation protocols will be verified comparing them to the no-treatment group in terms of incidence of complications.

Overall study duration will be 12 years: 2 years to enroll all the patients and 10 years to complete the last follow-up. Primary data analysis is planned after the completion of the 1-year follow-up visits.

• Study Type: Interventional
• Enrollment (Estimated): 159
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marco Delcogliano, MD; Phone Number: +41 (0)91 811 66 56; Email: marco.delcogliano@eoc.ch
• Study Contact Backup: Name: Christian Candrian, MD, Prof; Phone Number: +41 (0) 91 811 61 23; Email: christian.candrian@eoc.ch

Study Locations

• Switzerland
  • Lugano, Switzerland, 6900
    • Recruiting
    • Ospedale Regionale di Lugano Civico e Italiano
    • Contact: Christian Candrian, MD, Prof; Phone Number: +41 (0)91 811 7029; Email: christian.candrian@eoc.ch

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients undergoing unilateral primary TKA at the Ospedale Regionale di Lugano.
• Patients with a BMI >18.5 and <35.
• Patients able to provide informed consent and follow all the study procedures as indicated by the protocol.
• Informed Consent as documented by signature (Appendix Informed Consent Form).

Exclusion Criteria:

• Contraindications to steroids.
• Revision TKA.
• Active steroid therapy.
• Women who are pregnant or breast feeding.
• Presence of other clinically significant concomitant disease states (ASA IV).
• Uncontrolled diabetes mellitus
• Known or suspected non-compliance, drug or alcohol abuse.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Previous enrolment into the current study.
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: arm-A Intra-venous dexamethasone; 9 mg of Intra-venous dexamethasone	Drug: Dexamethasone Sodium Phosphate 4 mg/ml intravenous; Perioperative intravenous injection of 3 ml of solution (9mg of dexamethasone); Other Names: Mephameson
Experimental: arm-B intra-articular dexamethasone; 9 mg of intra-articular dexamethasone	Drug: Dexamethasone Sodium Phosphate 4 mg/ml intra-articular; Perioperative intra-articular injection of 3 ml of solution (9mg of dexamethasone); Other Names: Mephameson
No Intervention: arm-C routine; No steroid supplementation or other drugs will be added to the routinely performed anaesthesia protocol in the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean daily pain at rest during the first 3 days on a 0-10 numeric rating scale	Mean daily pain at rest during the first 3 days reported on a 0-10 numeric rating scale (NRS) by the patients. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no pain and 10 reflecting the worst possible pain.	3 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative knee pain during the first 6 weeks after surgery on a 0-10 numeric rating scale	Pain reported on 0-10 numeric rating scale (NRS) during the first 6 weeks and documented with a mobile application (developed at our Institution) that will ask the patients to report pain twice a day (once in the morning, once in the evening). Comparison will be performed in terms of mean daily pain during the first 6 weeks and mean daily pain during every single week. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no pain and 10 reflecting the worst possible pain.	6 weeks after surgery
Post-operative knee pain during the first 10 years after surgery	reported on 0-10 NRS at 3, 6, 12, 24, 60 and 120 months using a questionnaire. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no pain and 10 reflecting the worst possible pain.	10 years
Post-operative function during the first 6 weeks after surgery	reported on 0-10 NRS 8see above) during the first 6 weeks, documented with a mobile application developed by our institution that will ask the patients to report pain twice a day (once in the morning, once in the evening). Comparison will be performed in terms of mean daily pain during the first 6 weeks and mean daily pain during every single week. Furthermore, pain trajectories will be created. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating the worst possible function and 10 reflecting the best possible function.	6 weeks
Post-operative knee function during the first 10 years after surgery	reported on 0-10 NRS at 3, 6, 12, 24, 60 and 120 months using a questionnaire. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating the worst possible function and 10 reflecting the best possible function.	10 years
Post-operative knee outcome on Western Ontario and McMaster Universities Arthritis Index (WOMAC)	Questionnaire at 2 and 6 weeks, and at 3, 6, 12, 24, 60 and 120 months. The WOMAC questionnaire is composed of 3 sub-scores that evaluate pain (5 questions, 0-20 points), stiffness (2 questions, 0-8 points), and function (17 questions, 0-68 points) and is a validated patient-reported outcome measure (PROM) to evaluate knee osteoarthritis. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	10 years
Knee conditions on Knee society score (KSS)	Questionnaire at 2 and 6 weeks, and at 3, 6, 12, 24, 60 and 120 months. The original KSS has a "Knee Score" section (7 items) and a "Functional Score" section (3 items). Both sections are scored from 0 to 100 with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions.	10 years
Quality of pain on PainDETECT questionnaire	Questionnaire at 2 and 6 weeks, and at 3, 6, 12, 24, 60 and 120 months. PainDETECT consists of seven questions that address the quality of pain symptoms; it is completed by the patient and no physical examination is required. A score ≤12 indicates that pain is unlikely to have a neuropathic component (< 15%), while a score of ≥19 suggests that pain is likely to have a neuropathic component (> 90%). An intermediate score (≥13, ≤18) indicates a possible neuropathic component .	10 years
Patient satisfaction: numeric rating scale (NRS)	Patient satisfaction reported on 0-10 numeric rating scale (NRS) at 3, 6, 12, 24, 60 and 120 months using a questionnaire. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating that patient is not satisfied at all and 10 reflecting that patient is totally satisfied.	10 years
Post-operative nausea incidence	incidence (on a 0-10 NRS) of nausea will be evaluated in the first post-operative days. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no nausea and 10 reflecting the maximum intensity of nausea.	During Hospitalization, approximately 3 days
Post-operative nausea intensity	intensity (on a 0-10 NRS) of nausea will be evaluated in the first post-operative days. The 0-10 NRS consists in a single 11-point numeric scale, with 0 indicating no nausea and 10 reflecting the maximum intensity of nausea.	During Hospitalization, approximately 3 days
Post-operative opioids and analgesic drugs consumption	Medication Quantification Scale (MQS) score will be used to evaluate analgesic drug consumption. Medication Quantification Scale (MQS) scor is calculated for each medication by taking a consensus-based detriment weight for a given pharmacologic class and multiplying it by a score for dosage. The calculated values for each medication are then summed for a total MQS score. The score can provide a useful point measure of medication usage for any pain medication regimen.	During Hospitalization, approximately 3 days
Post-operative C-Reactive Protein (CRP)	Hematic C-Reactive Protein in mg/L will be evaluated as index of post-operative inflammatory response.	every days 3 days from surgery
Post-operative erythrocyte sedimentation rate (ESR)	Erythrocyte sedimentation rate (mm/h) will be evaluated as index of post-operative inflammatory response.	every days 3 days from surgery
Time from surgery to first mobilization		During Hospitalization, approximately 1 days
Time needed for climbing stairs the first time		approximately 1 week
Length of hospital stay		approximately 1 week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with treatment-related adverse events	The safety of I.V. and I.A. dexamethasone supplementation will be evaluated in terms of: rate of serious adverse events related to steroid supplementation, rate of prosthetic joint infections, rate of wound infections, rate of wound healing problems. Furthermore, glycaemia will be evaluated daily during the first three days after surgery. To delineate a complete safety profile of dexamethasone supplementation, all treatment related adverse events will be reported.	10 years

Collaborators and Investigators

• Sponsor: Christian Candrian
• Investigators: Principal Investigator: Christian Candrian, MD, Prof., EOC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2032

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: surgery; Knee; arthroplasty; replacement
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Dexamethasone 21-phosphate
• Other Study ID Numbers: ORL-ORT-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not foreseen

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