GENIFEM Trial: Postoperative Pain After Total Knee Arthroplasty (TKA)

Study Overview
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Brief Summary
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Motor-sparing analgesic interventions for patients undergoing total knee arthroplasty (TKA) are a key component of fast-track surgery. The investigators want to estimate treatments effects, inclusion rate, and feasibility of conducting a future randomized controlled superiority trial and to assess whether the short-term postoperative analgesic effect and ambulation after a Genicular - Infiltration Between Popliteal Artery and Capsule of Knee (iPACK) block in patients undergoing unilateral primary TKA is superior to Femoral triangle - iPACK block and Local Infiltration Analgesia (LIA). The study is a prospective, double-blind, triple-arm superiority pilot randomised controlled trial with a randomization rate 1:1:1.Group I will receive a Genicular - iPACK block, group II a Femoral Triangle - iPACK block and group III LIA. The primary study outcome is the proportion of patients that are able to mobilise (defined as walk 10 meters with assistance) with a numerical rating scale (NRS) of equal or less than 4 without the use of opioids at 4-6 hours after TKA. Secondary outcomes are efficacy (measured in NRS, total morphine consumption, total morphine titrations), functionality (quadriceps strength, timed-up-and-go, 6-minute walk test, inpatient falls), frequency of opioid related adverse events, discharge readiness, patient satisfaction, health-related quality of life, length of stay (LOS), complications after TKA and adverse events related to the study interventions.

Detailed Description
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Total knee arthroplasty (TKA) is one of the most frequently performed orthopedic surgical procedures for the treatment of osteoarthritis of the knee. Fast-tract recovery protocols emphasize the importance of early mobilization and physiotherapy to improve functional recovery, reduce postoperative complications, and decrease the economic burden of TKA. As the patients having TKA typically have severe pain postoperatively, multimodal analgesic regimen in many institutions includes interventional analgesia modality, such as nerve blocks, to facilitate early mobilization. At this time however, no universal recommendation exists on what constitutes the optimal nerve block technique that provides favorable balance between motor sparing for ambulation and analgesia. Various motor-sparing nerve blocks (e.g., femoral triangle block, adductor canal block, obturator nerve blocks, Infiltration Between Popliteal Artery and Capsule of Knee (iPACK), genicular nerve block and Local Infiltration Analgesia (LIA)) are viable options for interventional analgesia in patients undergoing TKA. By this study in patients having TKA, the investigators aim to compare the analgesia and ambulation between the genicular nerve block iPACK versus Femoral triangle nerve block + iPACK versus LIA.

Official Title
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Genicular Nerve Block Versus Femoral Triangle Nerve Block Versus LIA for Postoperative Analgesia After Total Knee Arthroplasty: A Pilot Randomized Controlled Superiority Trial

Conditions
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Analgesia, Total Knee Arthroplasty

Intervention / Treatment
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* Procedure: Genicular nerve block-iPACK group
* Procedure: Femoral triangle block-iPACK group
* Procedure: Local infiltration analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age at screening Scheduled to undergo elective primary unilateral TKA American Society of Anaesthesiologists (ASA) physical status 1, 2 or 3 Mentally competent to provide informed consent, to report pain intensity and to use patient-controlled analgesia Physically able to perform independently the baseline functionality tests Exclusion Criteria: Obesity (BMI>40) Previous open knee surgery Revision TKA or bilateral TKA Contraindication to the following study medication: ropivacaine, morphine, midazolam, ketorolac, propofol, remifentanil, clonidine, dexamethasone, acetaminophen Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments Chronic widespread pain Radicular pain in index legClinical Study Protocol Version 1.0 Preoperative strong opioid use within 3 days before surgery (with the exception of weak opioids: tramadol and codeine) Any chronic neuromuscular deficit affecting the peripheral nerves or muscles of the surgical extremity Impaired kidney function (Chronic kidney disease (CKD) G4-G5 according to Kidney Disease: Improving Global Outcomes (KDIGO) classification) Alcohol or drug abuse Pregnant, nursing or planning to become pregnant before treatment. Women of reproductive age will be tested on pregnancy prior to start of the study. Participants who get pregnant after the treatment during the follow-up period will not be excluded

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Genicular nerve block-iPACK group<br>Genicular nerve block-iPACK group (performed by anaesthesiologist) Method: Ultrasound and nerve stimulation guided injection Genicular nerve block will be performed on the the superomedial, the superolateral, the inferomedial and inferolateral genicular nerve. Drug: a total of 30 ml of ropivacaine 0.5% (150 mg) will be used for this treatment arm. | Procedure: Genicular nerve block-iPACK group<br>* Group 1: Genicular nerve block-iPACK group (performed by anaesthesiologist) Method: Ultrasound and nerve stimulation guided injection Drug: a total of 30 ml of ropivacaine 0,5% (150 mg) will be used<br>|
| Active Comparator: Femoral triangle block-iPACK group<br>Femoral triangle block-iPACK group (performed by anaesthesiologist) Method: Ultrasound and nerve stimulation guided injection Drug: a total of 30 ml of ropivacaine 0.5% (150 mg) will be used for this treatment arm | Procedure: Femoral triangle block-iPACK group<br>* Group 2: Femoral triangle block-iPACK group (performed by anaesthesiologist) Method: Ultrasound and nerve stimulation guided injection Drug: a total of 30 ml of ropivacaine 0,5% (150 mg) will be used<br>|
| Active Comparator: Local Infiltration Analgesia (LIA)<br>LIA (performed by surgeon) Method: Blind injection Drug: a total of 200 ml of 0.2% ropivacaine will be used (400 mg). Of this, 150 ml of ropivacaine 0.2% will be mixed with 1 mg of adrenaline. | Procedure: Local infiltration analgesia<br>* Group 3: LIA (performed by surgeon) Method: Blind injection Drug: a total of 200ml of 0.2% ropivacaine will be used (400mg). Of this, 150ml of ropivacaine 0.2% will be mixed with 1mg of adrenaline.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessed by NRS at rest and movement: 4 -6 hours after TKA | The main study outcome is the proportion of patients that have a numeral rating scale (NRS) <4 during mobilization without morphine at 4-6 hours after TKA. Mobilisation will be defined as walking 10 meters with walking aids or an assistant. NRS is a unidimensional, subjective measurement of pain intensity, expressed by the patient as a number between 0 and 10. It is a 11 point scale in which 0 equals no pain and 10 maximal pain. NRS at rest will also be determined | 4 to 6 hours after TKA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessed by NRS | NRS is determined at rest and movement at 24 hours, 48 hours, 72 hours and 1 month after TKA. NRS is a unidimensional, subjective measurement of pain intensity, expressed by the patient as a number between 0 and 10. It is a 11 point scale in which 0 equals no pain and 10 maximal pain. | 24 hours, 48 hours, 72 hours and 1 month | 
| Post-operative morphine consumption and titration | The amount of morphine that the patient demanded and that was given will be determined at 4-6 hours, 24 hours, 48 hours and 72 hours after TKA | 4-6 hours, 24 hours, 48 hours and 72 hours after TKA | 
| Quadriceps strength pre-and post operative | quadriceps strength measured in maximum voluntary isometric contraction (MVIC) at baseline (pre-operative), 4-6 hours, 24 hours, 48 hours after TKA | baseline, 4-6 hours, 24 hours, and 48 hours after TKA | 
| 6-minute walking test pre-and post operative | The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The 6 minute walking test will be performed at baseline (pre-operative), 24 hours, 48 hours and 72 hours after TKA | baseline, 24 hours, 48 hours and 72 hours after TKA | 
| Timed up and go pre- and post operative | In the timed up and go test, subjects are asked to rise from a standard armchair, walk to a marker 3 m away, turn, walk back, and sit down again. The results are expressed in minutes or seconds. The timed up and go test will be performed at baseline (pre-operative), 24 hours, 48 hours and 72 hours after TKA | baseline, 24 hours, 48 hours and 72 hours after TKA | 
| Health status assessed by WOMAC: pre- and post-operative | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a widely used self-administered health status measure used in assessing pain, stiffness, and function in patients with osteoarthritis of the knee. The test questions are scored on a scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The questionnaire will be performed at baseline (pre-operative) and 1 month after TKA | baseline and 1 month after TKA | 
| The change in health-related quality of life assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire | The EQ-5D-5L is a patient-reported generic measure of HRQoL comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Responses to the 5 items (one for each dimension) result in a patient's health state that can be transformed into a utility score ranging between 0 (death) and 1 (full health), representing the quality of life of the health state. | baseline and 1 month after TKA | 
| Assessment of anxiety and depression by the Hospital Anxiety and Depression Scale (HADS) questionnaire | HADS is developed to detect anxiety and depression in patients with physical health problems. The questionnaire consists of 14 items: 7 items to measure anxiety and 7 items to measure depression | baseline and 1 month after TKA | 
| Measurement of patient satisfaction by the patient satisfaction scale | The patient satisfaction scale is measured in a 5-point Likert scale with response categories consisting of very satisfied, somewhat satisfied, neutral, somewhat dissatisfied, and very dissatisfied | 72 hours and 1 month after TKA | 
| Assessment of pain experience by the Pain Catastrophizing Scale (PCS) | The PCS is often used in clinical settings to measure catastrophic thinking related to pain. The 13 item questionnaire consists of 3 subscales (magnification, rumination and helplessness) and asks patients to reflect on past painful experiences and to indicate the degree on which they experiences each of 13 thoughts of feelings on a 5- point scale (0 not at all and 4 all the time). | baseline and 1 month after TKA | 
| Nerve block time | (time from first needle insertion to final needle exit) | per-operative | 
| Number and type of complications of TKA | Complications of TKA (e.g., transfusions, prevalence of venous thrombo-embolic event, infection…) will be assessed per - and post-operative | Through study completion, up to 1 month after randomisation and study intervention | 
| Discharge readiness | The discharge readiness will be compared between the three groups. Discharge readiness is assessed by means of the following: Pain is under control (<4) with oral painkillers Wound is dry (not purulent) Knee flexion is possible over 70 degrees Patients are self-sustainable with crutches The discharge readiness is described as yes or no. | Through study completion, up to 1 month after randomisation | 
| Length of stay | The length of stay will be compared between the three groups by counting the number of days in the hospital | Through study completion, up to 1 month after randomisation | 
| Number of hospital readmissions (due to knee related problems at 1 month) | The readmission status of patients will be compared between groups after 1 month of TKA. | 1 month after TKA | 
| Safety assessment by reporting adverse events | Throughout the study, adverse events related to the intervention will be collected. | Through study completion, up to 1 month after randomisation | 
| Frequency of opioid related adverse event | The frequency of opioid related adverse event will be assessed from the start of surgery until 72 hours after TKA | 0 hours, 4-6 hours, 24 hours, 48 hours and 72 hours after TKA | 
| Attributable mortality during the trial | Mortality which is attributable to study interventions, surgical procedure, underlying condition or other relevant reasons will be investigated during the trial (perioperative, until discharge) | during hospitalisation, an average of 3 days | 
| Inpatient fall | The risk of inpatient fall will be assessed during hospital stay. | during hospitalisation, an average of 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genicular block, iPACK, Local Infiltration Analgesia (LIA), Femoral triangle nerve block, Postoperative analgesia, Total knee arthroplasty