Analgesic Efficacy of Preemptive Stepwise Infiltration Anesthesia for Perioperative Analgesia After TKA

October 16, 2024 updated by: Xinyu Fang, First Affiliated Hospital of Fujian Medical University

Analgesic Efficacy of Preemptive Stepwise Infiltration Anesthesia for Perioperative Analgesia After Total Knee Arthroplasty: a Prospective Double-blind Randomized Controlled Clinical Trial

This is a single-center prospective cohort study in which patients were evaluated by inclusion and exclusion criteria before total knee arthroplasty (TKA). Eligible patients will be included in this study after signing the informed consent form. Before TKA, the patients will be randomly assigned to either a preemptive stepwise infiltration anaesthesia (PSIA) group or a postoperative local infiltration analgesia (PLIA) group and administered different pain management protocols during surgery. Clinical evaluation will be conducted at baseline, before surgery, and at 6, 12, 24, 48, and 72 hours postoperatively, as well as during follow-up visits at 3 weeks, 6 weeks and 6 months postoperatively. All patients voluntarily participated in the study and signed informed consent. During the treatment period, all prospective patients underwent clinical evaluation at the end of total knee arthroplasty and 6, 12, 24, 48, 72, and 96 weeks later, aimed at comparing the postoperative pain and inflammatory response between PSIA and PLIA, to explore the optimal perioperative analgesic modality for TKA.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single-center prospective cohort study in which patients were evaluated by inclusion and exclusion criteria before total knee arthroplasty (TKA). This study aims to recruit 110 patients across a single centre over 1 year. Eligible patients will be included in this study after signing the informed consent form. Before TKA, the patients will be randomly assigned to either a preemptive stepwise infiltration anaesthesia (PSIA) group or a postoperative local infiltration analgesia (PLIA) group and administered different pain management protocols during surgery. Clinical evaluation will be conducted at baseline, before surgery, and at 6, 12, 24, 48, and 72 hours postoperatively, as well as during follow-up visits at 3 weeks, 6 weeks and 6 months postoperatively. The primary outcomes are the amount of morphine consumed within 0-24 hours postsurgery and the visual analogue scale (VAS) score postsurgery. Secondary outcomes include the time to first rescue analgesia, total morphine consumption during hospitalization, postoperative joint function (measured by the Hospital for Special Surgery [HSS] score and knee joint range of motion [ROM]), intraoperative bleeding and serological indicators. All patients voluntarily participated in the study and signed informed consent. During the treatment period, all prospective patients underwent clinical evaluation at the end of total knee arthroplasty and 6h, 12h, 24h, 48h, 72h, 3 weeks, 6 weeks and 6 months later, aimed at comparing the postoperative pain and inflammatory response between PSIA and PLIA, to explore the optimal perioperative analgesic modality for TKA. Statistical analyses utilizing regression models and survival analysis will be conducted to assess the relationships between the pain management method and postoperative pain and efficacy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
110

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Xinyu Fang, MD
  • Phone Number: 18084768503 Ext. 86
  • Email: 9738006@qq.com

Study Locations

  • China
    • Fujian
      • Fuzhou, Fujian, China
        • Recruiting
        • The First Affiliated Hospital of Fujian Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Patients must meet all of the following criteria to be eligible for inclusion:

  1. Clinical diagnosis of primary unilateral knee osteoarthritis (KOA), confirmed by imaging as KOA (Kellgren-Lawrence score ≥2). The patient was scheduled for initial unilateral total knee arthroplasty (TKA) at our hospital.
  2. Preoperative American Society of Anaesthesiologists (ASA) score ranging from 1 to 3. Surgeons deemed the patient eligible for TKA based on the evaluation criteria.
  3. Participants aged 18 years or older, both male and female.
  4. Ability to provide informed consent and sign a written informed consent form.
  5. The ability to comprehend the research requirements and willingness to cooperate with the study instructions.

Exclusion Criteria:

Patients will be excluded if they meet any of the following criteria:

  1. Previous knee surgery on the operative knee or a history of infection in the operative knee.
  2. Patients diagnosed with conditions other than osteoarthritis (including rheumatoid arthritis, traumatic arthritis, septic arthritis and haemophilic arthritis).
  3. Severe osteoarthritis (including flexion contracture >30° or varus/valgus deformity >30° and the use of unconventional arthroplasty components due to complex joint pathology [e.g., restrictive prostheses]).
  4. Allergy to the investigational drug.
  5. The presence of neuromuscular dysfunction on the operative side.
  6. Dependence on anaesthesia drugs (defined as the use of opioid or local anaesthetic drugs exceeding 100 mg of morphine equivalents per week to control preoperative pain for more than 3 months).
  7. Poor overall health conditions, including but not limited to a glycated haemoglobin level exceeding 12%; blood pressure exceeding 170/110 mmHg; myocardial infarction, stroke, transient ischaemic attack, acute congestive heart failure, or any acute coronary events within the past 6 months; severe hepatic or renal dysfunction; and pregnancy or lactation.
  8. Concurrent participation in clinical trials other than this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: preemptive stepwise infiltration anaesthesia(PSIA) group
Drugs：A cocktail of anaesthetics (30 mg of ropivacaine, 0.3 mg of adrenaline) will be prepared, diluted with normal saline to 120 mL, and divided into two equal parts(Cocktail A[CA] and Cocktail B[CB]), with CB containing 8 mg of added betamethasone (each 1 ml of the compound contains 5 mg betamethasone dipropionate [calculated as betamethasone] and 2 mg of betamethasone sodium phosphate [calculated as betamethasone]).
Procedure: preemptive stepwise infiltration anaesthesia(PSIA)
For PSIA patients, the anaesthetic is administered in stages. Initially, CA is injected at the incision site before the medial parapatellar incision. Following skin incision, more CA is injected into the subcutaneous tissue. After exposing the fascial layer and joint capsule, CA is used around the patellar tendon, and then CB is injected into the joint capsule and surrounding muscles. Additional CB is applied to the synovium and soft tissues after the joint cavity is opened, and more is used in the posterior joint capsule after bone resection.
Active Comparator: postoperative local infiltration analgesia(PLIA) group
Drugs: the same preoperative preparation and treatment with the anaesthesia cocktail formulation as those in the PSIA group.
Procedure: postoperative local infiltration analgesia(PLIA)
Before standardized TKA and implantation of the prosthesis, 30-40 mL of CB will be used to infiltrate the synovium and whole joint capsule. Subsequently, the joint cavity, subcutaneous tissue, and skin will be closed layer by layer using routine procedures. After the skin is closed, 30-40 mL of CA will be injected into the skin and subcutaneous tissue.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Postoperative morphine consumption within the first 24 hours
Time Frame: the first 24 hours after TKA
Postoperative morphine consumption within the first 24 hours includes both routine analgesia and rescue analgesia, which will be converted to oral morphine equivalents (OMEs)
the first 24 hours after TKA
. Postoperative visual analogue scale (VAS) scores at 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 3 weeks, 6 weeks and 6 months
Time Frame: 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 3 weeks, 6 weeks and 6 months after TKA
VAS scores are the most commonly used indicator for assessing the intensity of patient pain (15). The scale ranges from "0" to "10", where "0" indicates no pain and "10" represents the most severe pain that is unbearable. Patients will rate their pain based on subjective perceptions. In this trial, VAS scores will be recorded once before TKA. The VAS scores will be assessed separately for the resting and flexion states. If the patient's hospitalization period is shorter than 72 hours, the VAS score at discharge will be recorded instead of that at 72 hours. Studies have shown that some patients still experience joint pain six months after TKA. The VAS scores of patients at 6 months after TKA will be evaluated. A VAS score of 4 or above is defined as "chronic persistent pain after TKA." The results will be used to evaluate whether PSIA can reduce pain after TKA.
6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 3 weeks, 6 weeks and 6 months after TKA

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Postoperative time to first rescue analgesia
Time Frame: up to 3 days
Rescue analgesia will be initiated when the patient reports local knee joint pain on the operative side with a VAS score > 4. The specific steps will be implemented as described previously. The time to rescue analgesia will be recorded.
up to 3 days
Total morphine consumption during hospitalization
Time Frame: through study completion, an average of 6 months
It will be converted to total morphine equivalents and will include both the postoperative routine pain management regimen and rescue analgesia.
through study completion, an average of 6 months
The Hospital for Special Surgery Knee Score (HSS)
Time Frame: 3 weeks, 6 weeks and 6 months postoperatively
The Hospital for Special Surgery Knee Score (HSS) is a patient-reported questionnaire specific to the knee joint, with a total score of 100 points. It comprises six scoring components: pain (30 points), function (22 points), range of motion (18 points), muscle strength (10 points), knee deformity (10 points) and stability (10 points). Additional points are deducted for the use of assistive devices, extension lag and varus deformity: up to 3 points for assistive device use, up to 5 points for extension lag and 1 point deducted for every 5 degrees of varus deformity. The scores are classified as follows: ≥ 85 as "Excellent", 70-84 as "Good", 60-69 as "Fair", and < 60 as "Poor". The HSS score is widely praised for its perceived ease of use and quick recording and has been shown to be an effective and reliable measure for assessing the efficacy of TKA.
3 weeks, 6 weeks and 6 months postoperatively
Range of motion (ROM)
Time Frame: 3 weeks, 6 weeks and 6 months postoperatively
The range of motion (ROM) will be measured with a protractor thrice daily at 6-hour intervals, and the best value on each day will be used in the analysis. The range of motion (ROM) is from 0 to 180 degrees. The larger the angle, the more satisfactory the recovery of joint function.
3 weeks, 6 weeks and 6 months postoperatively
Direct intraoperative bleeding
Time Frame: 24 hours postoperatively
Intraoperative bleeding will be recorded directly by anesthesiologists (mL).
24 hours postoperatively
Indirect intraoperative bleeding
Time Frame: 24 hours postoperatively
Intraoperative bleeding will be estimated by subtracting the preoperative hemoglobin level from the hemoglobin level measured 24 hours postoperatively.
24 hours postoperatively
Complete blood count
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
A complete blood count (CBC) can reflect the patient's postoperative inflammatory status. It measures various components of the blood, including white blood cells, red blood cells, and platelets, which can indicate the presence of inflammation or infection. An elevated white blood cell count, for example, is often associated with an inflammatory response.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
C-reactive protein (CRP)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
C-reactive protein (CRP) can reflect the patient's postoperative inflammatory status.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Erythrocyte sedimentation rate (ESR)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Erythrocyte sedimentation rate (ESR) can reflect the patient's postoperative inflammatory status.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Interleukin-6 (IL-6)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Interleukin-6 (IL-6) can reflect the patient's postoperative inflammatory status.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Total bilirubin (TB)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Total bilirubin will be used to evaluate the impacts of surgical trauma and medications on patients.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Derect bilirubin (DB)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Derect bilirubin will be used to evaluate the impacts of surgical trauma and medications on patients.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Aspartate aminotransferase (AST)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Aspartate aminotransferase will be used to evaluate the impacts of surgical trauma and medications on patients.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Alanine aminotransferase (ALT)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Alanine aminotransferase will be used to evaluate the impacts of surgical trauma and medications on patients.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Creatinine (Cr)
Time Frame: 72 hours, 3 weeks, 6 weeks and 6 months postoperatively
Creatinine will be used to evaluate the impacts of surgical trauma and medications on patients.
72 hours, 3 weeks, 6 weeks and 6 months postoperatively

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Age
Time Frame: through study completion, an average of 6 months
Age in years will be obtained from the electronic medical records system.
through study completion, an average of 6 months
Sex
Time Frame: through study completion, an average of 6 months
Sex (male or female) will be obtained from the electronic medical records system.
through study completion, an average of 6 months
Operative site
Time Frame: through study completion, an average of 6 months
Operative site (left or right) will be obtained from the electronic medical records system.
through study completion, an average of 6 months
BMI
Time Frame: through study completion, an average of 6 months
Weight (kg) and height (m) will be combined to report BMI in kg/m^2, which will be obtained from the electronic medical records system. This information will be collected by the same evaluator and used to calculate the age-corrected Charlson Comorbidity Index (aCCI), baseline ROM, HSS score and VAS score for these patients.
through study completion, an average of 6 months
Time of operation
Time Frame: through study completion, an average of 6 months
Inpatient data will include the operative time and time to discharge. These inpatient data will be sourced from the electronic medical records system and used to evaluate the impacts of PSIA and PLIA on the surgical process and postoperative recovery.
through study completion, an average of 6 months
Operative time
Time Frame: through study completion, an average of 6 months
Operative time will be sourced from the electronic medical records system and used to evaluate the impacts of PSIA and PLIA on the surgical process and postoperative recovery.
through study completion, an average of 6 months
Time to discharge
Time Frame: through study completion, an average of 6 months
Time to discharge will be sourced from the electronic medical records system and used to evaluate the impacts of PSIA and PLIA on the surgical process and postoperative recovery.
through study completion, an average of 6 months
Incidence of Adverse events (AEs)
Time Frame: through study completion, an average of 6 months
Adverse events (AEs) are adverse medical events that occur in clinical trial subjects after receiving treatment. In this study, total AEs will be mainly categorized into local AEs and systemic AEs. Local AEs include but are not limited to prolonged wound drainage (wound drainage persists on postoperative day 3, and the drainage area of the wound dressing is greater than 2×2 cm , poor wound healing and prosthetic joint infection. Systemic AEs include but are not limited to deep vein thrombosis events, systemic infection and serious adverse events such as pulmonary embolism and death.
through study completion, an average of 6 months
Likert score
Time Frame: through study completion, an average of 6 months
We will use a Likert scale to evaluate participants satisfaction with each treatment phase at each assessment. This scale consists of 5 levels (very dissatisfied, dissatisfied, neutral, satisfied and very satisfied) from 1 to 5. After the final follow-up, the total score on the Likert scale for each participant will represent their overall satisfaction to date. The larger the score, the more satisfactory with the participants.
through study completion, an average of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Fujian Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Wenming Zhang, MD, First Affiliated Hospital of Fujian Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 30, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 2, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 19, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 17, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MRCTA, ECFAH of FMU|2024]576

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

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