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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Total Knee Replacement

Intervention / Treatment
-----------------
* Drug: Dexamethasone Sodium Phosphate 4 mg/ml intravenous
* Drug: Dexamethasone Sodium Phosphate 4 mg/ml intra-articular


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arm-A Intra-venous dexamethasone<br>9 mg of Intra-venous dexamethasone | Drug: Dexamethasone Sodium Phosphate 4 mg/ml intravenous<br>* Perioperative intravenous injection of 3 ml of solution (9mg of dexamethasone)<br>* Other names: Mephameson;|
| Experimental: arm-B intra-articular dexamethasone<br>9 mg of intra-articular dexamethasone | Drug: Dexamethasone Sodium Phosphate 4 mg/ml intra-articular<br>* Perioperative intra-articular injection of 3 ml of solution (9mg of dexamethasone)<br>* Other names: Mephameson;|
| No Intervention: arm-C routine<br>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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Knee, surgery, replacement, arthroplasty