Inflammatory Response Conventional Total Knee Replacement Versus Mako Total Knee Replacement

A Prospective Randomised Controlled Trial Comparing the Biochemical, Thermal, and Macroscopic Soft Tissue Outcomes in Conventional Jig-based Total Knee Arthroplasty Versus Mako Robotic-arm Assisted Total Knee Arthroplasty

Total knee Arthroplasty (TKA) is a highly effective treatment for knee osteoarthritis. Mid- to long-term follow-up studies have shown good clinical outcomes following TKA; despite these results, there is a high incidence of patient dissatisfaction; 20% of patients reporting dissatisfaction in otherwise uncomplicated procedures.

One reason for early dissatisfaction may be the trauma of surgery may lead to localised and systemic inflammatory responses that impair postoperative clinical recovery; this in turn influences long-term functional outcomes. Surgical techniques that limit the insult of surgery and help to restore the patient's native knee anatomy and kinematics may help to improve clinical outcomes, functional recovery, and patient satisfaction.

The technical objectives of surgery are to restore limb alignment, preserve the joint line, balance flexion and extension gaps, and maintain the normal Q angle for optimal patella tracking. Compromise to the periarticular soft tissue structures may compromise postoperative clinical and functional recovery, reduce stability, and decrease implant survivorship. In conventional jig-based (CO) TKA, bone cuts are most commonly performed using measured resection or gap balancing. The manual error associated with inadvertent soft tissue release during preparation for implantation or tissue damage from the saw blades is an accepted part of the procedure.

The evolution of surgical technology has led to the development of robotic-arm assisted TKA, which uses three dimensional images of the patient's native knee anatomy to guide bone resection and optimise implant positioning. The second-generation RIO Robotic Arm Interactive Orthopaedic system (Mako surgical) uses preoperative computerised tomography scans to build a computer-aided design (CAD) model of the patient's knee joint. The Mako robotic software processes this information to calculate the volume of bone requiring resection and creates a three-dimensional haptic window for the RIO robotic arm to resect.

In short, the robotic technology in TKA allows execution of the preoperative surgical plan without undue soft tissue release, inadvertent trauma from power tools, and minimal trauma to bone surfaces. Conceptually, this Mako TKA should have reduced soft tissue trauma and inflammatory response as assessed with inflammatory cytokines compared to CO TKA.

The overall aim of this single centre, prospective randomised controlled trial is to determine differences in the inflammatory response between CO TKA and Mako TKA.

A comprehensive range of local and systemic biochemical markers, thermal response, and macroscopic soft tissue injury outcomes between the two groups will be recorded and correlated to clinical and functional outcomes over 2-year postoperative. Patients undergoing CO TKA will form the control group and those undergoing Mako TKA will form the investigation group.

Study Overview

• Status: Completed
• Conditions: Arthritis; Knee Osteoarthritis; Surgery
• Intervention / Treatment: Device: Total Knee Arthroplasty

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient has symptomatic knee osteoarthritis requiring primary TKA
• Patient and surgeon are in agreement that TKA is the most appropriate treatment
• Patient is fit for surgical intervention following review by surgeon and anaesthetist
• Patient is between 18-80 years of age at time of surgery
• Gender: male and female
• Patient must be capable of giving informed consent and agree to comply with the postoperative review program
• Patient must be a permanent resident in an area accessible to the study site
• Patient must have sufficient postoperative mobility to attend follow-up clinics and allow for radiographs to be taken

Exclusion Criteria:

• Patient is not suitable for routine primary TKA e.g. patient has ligament deficiency that requires a constrained prosthesis
• Patient has inflammatory arthritis e.g. Rheumatoid arthritis
• Patient has local or systemic autoimmune disease
• Past medical history of cancer or chronic illness
• Patient has symptomatic arthritis of the contralateral knee

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional; Jig-based procedure	Device: Total Knee Arthroplasty; Surgical implantation of prosthetic knee using robotic-arm assist
Experimental: Robotic arm-assist; Mako robotic-arm assist based procedure	Device: Total Knee Arthroplasty; Surgical implantation of prosthetic knee using robotic-arm assist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum CRP level	Serum CRP level	48 hours post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reactive Protein (CRP)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Interleukin-1 beta (IL1 beta)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Interleukin-6 (IL6)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Tumour necrosis Factor alpha (TNFalpha),	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Creatine Kinase (CK)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Creatine Phosphokinase (CPK)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Full blood count (FBC)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Erythrocyte sedimentation rate (ESR)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Myoglobin (MG)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Lactate dehydrogenase (LDH)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
Urea and Electrolytes (U&Es)	Systemic inflammation as assessed by the serial measurement of serum inflammatory cytokines and enzyme markers of soft tissue injury	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days following TKA
IL-6	Local inflammatory response as assessed using intraarticular drain fluid	6 and 24 hours following surgery
Interleukin-8 (IL-8)	Local inflammatory response as assessed using intraarticular drain fluid	6 and 24 hours following surgery
TNFalpha	Local inflammatory response as assessed using intraarticular drain fluid	6 and 24 hours following surgery
Thermal response to inflammation	skin temperature over the operated knee joint preoperatively and postoperatively	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days.
Soft tissue injury prior to implantation of femoral and tibial prostheses	macroscopic examination of the periarticular soft tissues	28 days post op
Operating time	Operating time (minutes).	28 days post op
Time to discharge	Time to discharge (hours).	28 days post op
Pain in knee	Subjective score. Pain as assessed using the Visual analogue score (VAS) following surgery. Patient uses line delineated at left hand end with '0' and '10' at the right hand end. 0= no pain; 10 = the most pain. Patient indicates where they feel their pain fits onto this score.	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days
Analgesia requirements	Analgesia requirements following surgery	6 hours, 1 day, 2 days, 3 days, 7 days, and 28 days.
Oxford knee score (OKS)	Patient recorded outcome measure via questionnaire. 48 is best score and 0 worst score	Pre-op; 4 weeks post-op; 6 months post-op; 1 year post-op; 2 years post-op
Short form health survey of 12 items (SF-12)	Patient recorded outcome measure. Questions concerning attitudes to physical and mental heath with 12 questions combined to give overall norm-based values; higher score better, lower score worse.	Pre-op; 4 weeks post-op; 6 months post-op; 1 year post-op; 2 years post-op
Knee injury and osteoarthritis outcome score (KOOS)	Patient recorded outcome measure via questionnaire. 6 separate domains including pain, stiffness, quality of life, symptoms, and function; each domain creates percentage with overall cumulative percentage achieved; best score 100%	Pre-op; 4 weeks post-op; 6 months post-op; 1 year post-op; 2 years post-op
Western Ontario and Mcmaster Universities Arthritis Index (WOMAC)	Patient recorded outcome questionnaire evaluating pain, stiffness and disability in affected joint	Pre-op; 4 weeks post-op; 6 months post-op; 1 year post-op; 2 years post-op
European Quality of Life questionnaire with 5 dimensions for adults (EQ-5D)	Patient recorded outcome measure with 5 domains; score -1 to 1, with 1 being best score	Pre-op; 4 weeks post-op; 6 months post-op; 1 year post-op; 2 years post-op

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Stryker EU Operations BV
• Investigators: Study Chair: Fares S Haddad, UCL Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: December 6, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: total knee replacement; thermal; total knee arthroplasty; inflammation; biomechanical; mako robot; makoplasty; soft tissue injury
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 17/0742

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan

Drug and device information, study documents

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