## Protocol Section
### Identification Module
**NCT ID:** NCT06426641

**Brief Title:** Polyethylene Wear Particle Analysis of TKA

**Official Title:** Polyethylene Wear Particle Analysis of Total Knee Arthroplasty -International Multicenter Study-

#### Organization Study ID Info
**ID:** OMU 2023-108
#### Organization
**Class:** OTHER
**Full Name:** Osaka Metropolitan University
### Status Module
#### Completion Date
**Date:** 2028-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-28

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2027-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-12-05

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Mayo Clinic

**Class:** OTHER

**Name:** Istituto Ortopedico Rizzoli

**Class:** OTHER

**Name:** Hospital for Special Surgery, New York

#### Lead Sponsor

**Class:** OTHER

**Name:** Osaka Metropolitan University

#### Responsible Party

**Investigator Affiliation:** Osaka Metropolitan University

**Investigator Full Name:** Yukihide Minoda

**Investigator Title:** Associate professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is US Export:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study was to investigate whether polyethylene (Vitamin E-containing polyethylene), which has been newly introduced and widely used clinically as a biomaterial for tibial inserts in total knee arthroplasty, but whose mid- to long-term clinical results are still unknown, is more effective than conventional polyethylene.

Our goal is to clarify through an international multi-center joint study using in vivo polyethylene wear particle analysis, which the investigators developed as a method to provide early feedback, as to whether polyethylene wear debris production in vivo can be reduced.

**Detailed Description:** Anticipated medical contribution and significance In this study, the investigators investigate whether a newly introduced polyethylene (highly cross-linked polyethylene, vitamin E-containing polyethylene in vivo) can suppress wear debris production more than conventional polyethylene. If the newly introduced polyethylene can reduce wear debris production, it is expected to reduce failure of artificial joints in the future. However, if newly introduced polyethylene is actually increasing wear debris production, it could be an early alarm bell for surgeons around the world. In other words, the international and social impact of this research is extremely large.

Two unique requirements are necessary to carry out this research. Firstly, in vivo analysis of polyethylene wear particles is possible, and secondly, the number of surgical cases of revision knee arthroplasty targeted for investigation is large. The first requirement is that the applicants have published many English-language papers on in vivo polyethylene wear debris analysis, and that their facilities are the most suitable and fully capable of carrying out the analysis worldwide. be. The second requirement is that the investigators need to collaborate not only with our hospital but also with facilities that perform a large number of revision knee arthroplasty surgeries. Not only our hospital, but also our affiliated hospital, which is one of the facilities in Japan that performs the most knee joint surgeries (Naniwa Ikuno Hospital), and the hospital that performs the most knee joint surgeries worldwide (Mayo Clinic \[USA\]). , Hospital for Special Surgery \[USA\], Istituto Ortopedico Rizzoli \[Italy\]).

Research method In this study, the investigators conducted the following steps to determine the in vivo wear particles (number, size, and morphology) of conventional polyethylene, whose long-term results have already been clarified, and vitamin E-containing polyethylene, whose mid- to long-term results have not yet been clarified. Clarifying the difference \[Figure 3\].

Target of this research In this study, the investigators will focus on patients undergoing revision knee arthroplasty as a routine medical treatment.

First total joint replacement

* 30 patients using polyethylene containing Vitamin E
* 30 patients using conventional polyethylene (no highly cross-linking)
* 30 patients using conventional polyethylene (with highly cross-linking)

Accumulation of periarticular tissue In this study, the investigators will focus on patients undergoing revision knee arthroplasty as a routine medical treatment.

The test will be conducted after obtaining approval from the ethics committee at each facility and obtaining informed consent. The pericapsular tissue, which is removed during surgery and usually discarded, is obtained and fixed in formalin fixative. The tissue will be transported to the Department of Orthopedic Surgery, Osaka Public University Graduate School of Medicine for analysis. International transportation of tissues requires outsourcing to specialized companies with experience in transporting tissues from overseas.

Isolation of polyethylene wear debris The collected tissue around the joint capsule is immersed in 5M NaOH at 65°C for 1 hour to decompose the protein. Make a sucrose layer (5, 10, 20%) in a 14ml tube (14PA tube, Hitachi Koki Co, Ltd, Tokyo, Japan), add the dissolved solution, and place in an ultracentrifuge (CP100a, P28S1014 rotor, Hitachi Koki). Ultracentrifuge at 28,000 rpm \[103,7009g\] for 3 hours at 4°C. Prepare an isopropanol layer (0.90 and 0.96 g/mL) in a 40 ml tube (40PA tube, Hitachi Koki Co, Ltd, Tokyo, Japan), add the upper layer of sucrose layer, and centrifuge at 28,000 rpm (103,7009 g ) and perform ultracentrifugation at 4°C for 1 hour. The isopropanol interlayer is collected to isolate polyethylene wear debris.

Analysis of polyethylene wear debris The isopropanol interlayer is filtered through a 0.1 μm polycarbonate filter (VCTP 013-00, Millipore Corporation, Bedford, MA). Dry the polycarbonate filter, fix it on an aluminum pedestal (M4, Nisshin EM Co, Ltd, Tokyo, Japan), and apply platinum coating (E-1030 ion sputter, Hitachi Science Systems Ltd, Tokyo, Japan). Observe the polyethylene wear particles on the polycarbonate filter using a scanning electron microscope (S4700SI, Hitachi Ltd, Tokyo, Japan), and analyze the following items using an image analyzer (Mac Scope, Mitani Co, Tokyo, Japan).

* Number of polyethylene wear particles (number per 1g of tissue)
* Size (Equivalent circle diameter \[μm\])
* Shape (aspect ratio, roundness)

Comparison of iv vivo polyethylene wear powder morphology depending on polyethylene material The number, size, and form of polyethylene wear debris will be compared between conventional polyethylene, whose long-term results have already been clarified, and vitamin E-containing polyethylene, whose medium- to long-term results have not yet been clarified.

The investigators also investigated factors that affect polyethylene wear in vivo (age, height, weight, period from initial surgery to revision surgery, knee joint range of motion, knee prosthesis clinical score \[Knee Society Score, University of California at Los Angeles activity score\]).

Evaluation items (outcome) Main evaluation items: Polyethylene wear particle morphology (number of wear particles, equivalent circle diameter \[㎛\], aspect ratio, roundness) \[Reason for setting primary endpoints\] Because it is a standard evaluation item for evaluating polyethylene wear debris.

Secondary endpoints:

* Body mass index
* Knee joint range of motion
* Clinical score (2011Knee Society Score, Knee injury and Osteoarthritis Outcome Score for Joint Replacement, University of California at Los Angeles activity score) \[Reason for setting secondary endpoints\] Because it may affect the production of polyethylene wear debris.

Planned number of research subjects and basis for setting it (including cases where the number of research subjects is set without relying on statistical grounds) Total 90 cases

* 30 patients using polyethylene containing Vitamin E
* 30 patients using conventional polyethylene (no high cross-linking)
* 30 patients using conventional polyethylene (with high cross-linking) Rationale for setting: The target number of cases was determined from the number of cases at related institutions within the study period.

### Conditions Module

**Conditions:**

- Wear of Articular Bearing Surface of Prosthetic Joint

- Total Knee Arthroplasty

**Keywords:**

- Polyethylene wear particle

### Design Module

#### Bio Spec

**Description:** pericapsular tissue, which is removed during surgery

**Retention:** SAMPLES_WITHOUT_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 90

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** polyethylene containing Vitamin E

**Intervention Names:**

- Device: Polyethylene

**Label:** polyethylene containing Vitamin E

#### Arm Group 2

**Description:** conventional polyethylene (no highly cross-linking)

**Intervention Names:**

- Device: Polyethylene

**Label:** conventional polyethylene (no highly cross-linking)

#### Arm Group 3

**Description:** conventional polyethylene (with highly cross-linking)

**Intervention Names:**

- Device: Polyethylene

**Label:** conventional polyethylene (with highly cross-linking)

### Interventions

#### Intervention 1

**Arm Group Labels:**

- conventional polyethylene (no highly cross-linking)

- conventional polyethylene (with highly cross-linking)

- polyethylene containing Vitamin E

**Description:** There is no intervention

**Name:** Polyethylene

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** counts / g (tissue sample)

**Measure:** Number of polyethylene wear particles

**Time Frame:** Time of revision surgery

**Description:** Equivalent circle diameter (㎛)

**Measure:** Equivalent circle diameter of polyethylene wear particles

**Time Frame:** Time of revision surgery

**Description:** Aspect ratio

**Measure:** Aspect ratio of polyethylene wear particles

**Time Frame:** Time of revision surgery

**Description:** Roundness

**Measure:** Roundness of polyethylene wear particles

**Time Frame:** Time of revision surgery

#### Secondary Outcomes

**Description:** kg/m2

**Measure:** Body mass index

**Time Frame:** Time of revision surgery

**Description:** degrees

**Measure:** Knee joint extension angle

**Time Frame:** Time of revision surgery

**Description:** degrees

**Measure:** Knee joint flexion angle

**Time Frame:** Time of revision surgery

**Description:** 0(worse)-100(best)

**Measure:** 2011 Knee Society Score: An "Objective" Knee Score

**Time Frame:** Time of revision surgery

**Description:** 0(worse)-40(best)

**Measure:** 2011 Knee Society Score: A Patient Satisfaction Score

**Time Frame:** Time of revision surgery

**Description:** 0(worse)-15(best)

**Measure:** 2011 Knee Society Score: A Patient Expectation Score

**Time Frame:** Time of revision surgery

**Description:** 0(worse)-100(best)

**Measure:** 2011 Knee Society Score: A Functional Activity Score

**Time Frame:** Time of revision surgery

**Description:** 0(worse)-100(best)

**Measure:** Knee injury and Osteoarthritis Outcome Score for Joint Replacement

**Time Frame:** Time of revision surgery

**Description:** 1(worse)-10(best)

**Measure:** University of California at Los Angeles activity score

**Time Frame:** Time of revision surgery

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Patients undergoing revision knee arthroplasty within the study period
2. Patients over 20 years old
3. Patients who have received a sufficient explanation, have sufficient understanding, and have given their free written consent.
4. Patients who have passed 2 years or more since their first total knee arthroplasty

Exclusion Criteria:

1. Patients who are judged to be unsuitable as research subjects by the research physician

**Minimum Age:** 20 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Patients undergoing revision surgery

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Osaka

**Country:** Japan

**Facility:** Osaka Metroplitan Univerity

**Zip:** 545-8585

#### Overall Officials

**Official 1:**

**Affiliation:** Osaka Metropolitan University

**Name:** Yukihide Minoda, MD, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Minoda Y, Kobayashi A, Iwaki H, Iwakiri K, Inori F, Sugama R, Ikebuchi M, Kadoya Y, Takaoka K. In vivo analysis of polyethylene wear particles after total knee arthroplasty: the influence of improved materials and designs. J Bone Joint Surg Am. 2009 Nov;91 Suppl 6:67-73. doi: 10.2106/JBJS.I.00447. No abstract available.

**PMID:** 19884413

**Citation:** Minoda Y, Kobayashi A, Iwaki H, Miyaguchi M, Kadoya Y, Ohashi H, Yamano Y, Takaoka K. Polyethylene wear particles in synovial fluid after total knee arthroplasty. Clin Orthop Relat Res. 2003 May;(410):165-72. doi: 10.1097/01.blo.0000063122.39522.c2.

**PMID:** 12771827

## Derived Section

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M22972

- Name: Tocopherols

- Relevance: LOW

- As Found: Unknown

- ID: M17553

- Name: Vitamin E

- Relevance: LOW

- As Found: Unknown

- ID: M22975

- Name: Tocotrienols

- Relevance: LOW

- As Found: Unknown

- ID: M22969

- Name: alpha-Tocopherol

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: T466

- Name: Tocopherol

- Relevance: LOW

- As Found: Unknown

- ID: T467

- Name: Tocotrienol

- Relevance: LOW

- As Found: Unknown

- ID: T480

- Name: Vitamin E

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
