Clinical trial NCT06525610: Weight-Bearing CT Periprosthetic Distal Knee Fractures
Official title: Assessment of Bone Displacement Under Loading Following Periprosthetic Fracture Repair With Weight-Bearing CT
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Periprosthetic Fracture Around Prosthetic Joint Implant Knee
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2024-07-29
Enrollment: 21
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: \<1 week post-operation: 1 unloaded scan with the weight-bearing CT will be conducted 6 weeks: 1 unloaded and loaded scan with the weight-bearing CT. Subjects will get a one-time pre-paid, pre-addressed envelope with a DNA-free bag. They will place a stool sample in the bag collected on dry toilet paper and then send it to Dr. Jeremy Burton's lab at St. Joseph's Hospital for processing and analysis. Data will be processed at St. Joseph's Hospital site. Once DNA is extracted, the specimens will be destroyed and disposed. No further stool samples will be collected on follow-up visits.

1 year: 1 unloaded scan and 2 loaded scans with the weight-bearing CT will be conducted. A second loaded exam is performed at the 1-year visit as a "double exposure" exam to measure for clinically relevant measurement errors
Primary purpose: OTHER

Brief summary: Total knee arthroplasty (TKA), a knee implant surgery, is a treatment for end-stage knee osteoarthritis. In some cases, patients suffer an associated periprosthetic fracture, a broken bone that occurs around the implant of a TKA, they may not receive excellent care due to a lack of a trustworthy assessments for fracture healing in the research world. The prevalence of TKA surgeries is increasing annually and is expected to increase further due to an ageing population and obesity issue. By extension to this primary surgery, more Canadians will require an invasive revision surgery that risks patient morbidity and mortality. Thus, it is important to set a standard for fracture stabilization and bone healing assessments to lessen revision burdens and improve patient outcomes. CT imaging is the main clinical tool to evaluate implant stabilization in TKA, which can effectively visualize areas of incomplete bone ingrowth, bone growing into the implant, that may be hidden from overlapping bone and muscle tissue on plain x-rays. The purpose of this prospective study is to examine the efficacy of weight-bearing CT as a diagnostic tool for 21 participants who experienced a distal femur periprosthetic fracture and have underwent revision surgery using a fracture fixation plate and screws, internal splints that hold the bone pieces together. Participants will be scanned under loaded (applying weight on limb) and unloaded conditions. Radiographic outcomes, x-ray imaging from the weight-bearing CT, will be evaluated, including any movement of the bone segments and how they would relate to participants' reports of pain.

Detailed description: Total knee arthroplasty is the most cost-effective and successful treatment for knee joints with end-stage osteoarthritis, with more than 58,000 TKA surgeries in Canada in 2021-2022.1 The prevalence of TKA surgeries is increasing per year and is projected to rise due to an ageing population and obesity problems.1 In addition to the primary surgery, more than 4,000 Canadians require revision TKA surgery per year; the TKA revision burden is estimated to reach $13 billion by 2030 as a consequence of a substantial increase of 149% in primary surgeries by 2030 in the United States.1-3 Revision surgery is more invasive than primary surgery and poses the risk of increasing patient mortality rates, especially for older adults.3 Thus, it is imperative for surgeons to make an appropriate radiographic diagnosis of implant fixation and/or fracture healing, but many cases remain challenging to diagnose.4

In the orthopaedic literature, there is no consensus on a reliable definition criterion for long-bone non-unions, making the standardization of diagnoses difficult; the lack of a trustworthy assessment for component fixation and fracture healing can lead to patients receiving sub-optimal care.5 This can also limit the collection of evidence supporting the use of specific implant components, surgical techniques, and post-operative activity guidelines. Moreover, comparing healing results of different clinical studies for long-bone non-unions can become problematic due to different criteria being used.5 Radiographic features associated with loosening such as radiolucencies are often only appreciable for the cement-bone interface, rather than the cement-implant interface which is the most common site of failure causing loosening.4 Failure to properly diagnose fracture non-union leaves patients in pain with substantial morbidity, while unnecessary surgery risks significant complication. Given the increasing rates of TKA and associated predictions of increasing revision burden,6 along with ongoing debates over the superiority of certain implants or surgical techniques, there is an unmet need for better fixation and bone healing assessment.

Historically, radiostereometric analysis (RSA) has been the gold standard for measuring implant fixation.7 However, it remains a niche tool limited to clinical research because of its requirement for implanted marker beads and specialized equipment being accessible for a handful of labs in North America.7-8 Recently, multiple groups have developed approaches to perform RSA-like measurements using clinical CT scans for shoulder, hip, and knee replacements.9 The accuracy and precision of the "CT-RSA" methods are on par with conventional RSA and acceptable for clinical studies.10-15 It is predicted that there will be a greater uptake of CT-RSA than conventional RSA, but the technology is still in its infancy.9 The application of CT-RSA will undoubtedly be more inclusive as examinations can now be performed on patients who did not have marker beads implanted at the time of their original surgery, and CAD models of implants are not needed.16 Using a weight-bearing CT scanner is the most similar implementation of CT-RSA to conventional RSA, as exams can be acquired in unloaded and loaded positions.

Additionally, in the field of microbiome research, the gut microbiome is being investigated for its potential impacts on bone health and recovery. There are currently a few studies that have linked the intestinal microbiome having a beneficiary effect to fracture healing with a new concept referred to as the gut-bone axis.17 Moreover, the gut microbiome of patients with poor bone quality has previously been found to be altered.18 We will use stool samples to assess gut microbiome composition to see if patients with markers for poor bone quality could have increased migration.

The results of this proposed study will demonstrate the ability to precisely measure displacements between bone segments under loading following periprosthetic fracture repair with weight-bearing. These will be the first-ever measurements of distal femur periprosthetic fracture healing with weight-bearing CT-RSA. Demonstration of this will enable us to pursue future studies that are prospective in nature and may evaluate topics such as time to weight-bearing activities, different types of surgical reconstructions, and relationship between healing and bone quality/bone health. Other centres with access to weight-bearing CT will also benefit from this work. Usage of the weight-bearing CT may improve the generalizability of this approach and support it as a clinical diagnostic tool. For example, surgeons may better understand bone fragment motion over time and recommend appropriate postoperative activities for patients' weight-bearing tolerance. Therefore, the proposed study design will evaluate the ability to perform inducible displacement measurements following the surgical repair of distal femur periprosthetic fractures using weight-bearing CT.

Eligibility criteria: Inclusion Criteria:

* Recently underwent revision surgery for repair of a distal femur fracture surgery for total knee arthroplasty femoral component using a fracture fixation plate. Due to the study requiring the potential participant to be scanned \<1-week post-operation, the duration of "recently" will be defined as \<1 week post-operation.
* Age 50-90 years
* Body mass index up to 40kg/m2
* Able to provide informed consent
* Able and willing to do study assessments and follow instructions

Exclusion Criteria:

* Prior revision surgery on the targeted knee
* Does not understand English
* Undergoing and/or have undergone revision surgery for any other indication
* Received intramedullary nail or distal femur replacement
* Cannot independently stand on one leg in the weight-bearing CT during the inducible displacement exam

Primary outcomes:
measure: Weight-Bearing CT Scans
timeFrame: Scans obtained: <1-week post-operation, 6-weeks, and 1-year
measure: Pain and Function Questionnaires
timeFrame: <1-week post-operation, 6 weeks, and 1-year
Secondary outcomes:
measure: Stool sample
timeFrame: 6-week timepoint post-operation
Other outcomes:
Locations:
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Matthew Teeter, PhD
role: STUDY_DIRECTOR
affiliation: London Health Sciences Centre
name: Brent Lanting, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Farzan Mohammadreza, MSc
role: STUDY_CHAIR
affiliation: London Health Sciences Centre
name: Lyndsay Somerville, PhD
role: STUDY_CHAIR
affiliation: Western University
name: Patrick J Mixa, MD
role: STUDY_CHAIR
affiliation: London Health Sciences Centre
name: James Howard, MD
role: STUDY_CHAIR
References:
citation: Steele JR, Ryan SP, Jiranek WA, Wellman SS, Bolognesi MP, Seyler TM. Cost of Aseptic Revision Total Knee Arthroplasty at a Tertiary Medical Center. J Arthroplasty. 2021 May;36(5):1729-1733. doi: 10.1016/j.arth.2020.11.028. Epub 2020 Dec 17.
citation: Sinclair ST, Orr MN, Rothfusz CA, Klika AK, McLaughlin JP, Piuzzi NS. Understanding the 30-day mortality burden after revision total knee arthroplasty. Arthroplast Today. 2021 Oct 4;11:205-211. doi: 10.1016/j.artd.2021.08.019. eCollection 2021 Oct.
citation: Crellin CT, Pennings JS, Engstrom SM, Shinar AA, Polkowski GG, Martin JR. Aseptic tibial loosening: Radiographic identification remains a diagnostic dilemma. Journal of Orthopaedic Reports. 2023;2(4):100194. doi:10.1016/j.jorep.2023.100194
citation: Wittauer M, Burch MA, McNally M, Vandendriessche T, Clauss M, Della Rocca GJ, Giannoudis PV, Metsemakers WJ, Morgenstern M. Definition of long-bone nonunion: A scoping review of prospective clinical trials to evaluate current practice. Injury. 2021 Nov;52(11):3200-3205. doi: 10.1016/j.injury.2021.09.008. Epub 2021 Sep 10.
citation: Klug A, Gramlich Y, Rudert M, Drees P, Hoffmann R, Weissenberger M, Kutzner KP. The projected volume of primary and revision total knee arthroplasty will place an immense burden on future health care systems over the next 30 years. Knee Surg Sports Traumatol Arthrosc. 2021 Oct;29(10):3287-3298. doi: 10.1007/s00167-020-06154-7. Epub 2020 Jul 15.
citation: Aspinall GA, Dunbar MJ. Assessing clinical results and outcome measures. Surgical Treatment of Hip Arhtritis. 2009;30-36. Doi:10.1016/B978-1-4160-5898-4.00004-5
citation: Valstar ER, Gill R, Ryd L, Flivik G, Borlin N, Karrholm J. Guidelines for standardization of radiostereometry (RSA) of implants. Acta Orthop. 2005 Aug;76(4):563-72. doi: 10.1080/17453670510041574.
citation: Rohrl SM. "Great balls on fire:" known algorithm with a new instrument? Acta Orthop. 2020 Dec;91(6):621-623. doi: 10.1080/17453674.2020.1840029. Epub 2020 Nov 4. No abstract available.
citation: Angelomenos V, Mohaddes M, Itayem R, Shareghi B. Precision of low-dose CT-based micromotion analysis technique for the assessment of early acetabular cup migration compared with gold standard RSA: a prospective study of 30 patients up to 1 year. Acta Orthop. 2022 Apr 22;93:459-465. doi: 10.2340/17453674.2022.2528.
citation: Broden C, Sandberg O, Olivecrona H, Emery R, Skoldenberg O. Precision of CT-based micromotion analysis is comparable to radiostereometry for early migration measurements in cemented acetabular cups. Acta Orthop. 2021 Aug;92(4):419-423. doi: 10.1080/17453674.2021.1906082. Epub 2021 Apr 6.
citation: Engseth LHW, Schulz A, Pripp AH, Rohrl SMH, Ohrn FD. CT-based migration analysis is more precise than radiostereometric analysis for tibial implants: a phantom study on a porcine cadaver. Acta Orthop. 2023 Apr 27;94:207-214. doi: 10.2340/17453674.2023.12306.
citation: Broden C, Sandberg O, Skoldenberg O, Stigbrand H, Hanni M, Giles JW, Emery R, Lazarinis S, Nystrom A, Olivecrona H. Low-dose CT-based implant motion analysis is a precise tool for early migration measurements of hip cups: a clinical study of 24 patients. Acta Orthop. 2020 Jun;91(3):260-265. doi: 10.1080/17453674.2020.1725345. Epub 2020 Feb 14.
citation: Stigbrand H, Brown K, Olivecrona H, Ullmark G. Implant migration and bone mineral density measured simultaneously by low-dose CT scans: a 2-year study on 17 acetabular revisions with impaction bone grafting. Acta Orthop. 2020 Oct;91(5):571-575. doi: 10.1080/17453674.2020.1769295. Epub 2020 May 26.
citation: Eriksson T, Maguire GQ Jr, Noz ME, Zeleznik MP, Olivecrona H, Shalabi A, Hanni M. Are low-dose CT scans a satisfactory substitute for stereoradiographs for migration studies? A preclinical test of low-dose CT scanning protocols and their application in a pilot patient. Acta Radiol. 2019 Dec;60(12):1643-1652. doi: 10.1177/0284185119844166. Epub 2019 May 1. No abstract available.
citation: Sandberg OH, Karrholm J, Olivecrona H, Rohrl SM, Skoldenberg OG, Broden C. Computed tomography-based radiostereometric analysis in orthopedic research: practical guidelines. Acta Orthop. 2023 Jul 20;94:373-378. doi: 10.2340/17453674.2023.15337.
citation: Karačić A, Novak J, Ivković. Probiotics in bone fracture treatment? A narrative literature review. Microbiota and Host, 2023;1(1):e230003. doi: 10.1530/MAH-23-0003
citation: Das M, Cronin O, Keohane DM, Cormac EM, Nugent H, Nugent M, Molloy C, O'Toole PW, Shanahan F, Molloy MG, Jeffery IB. Gut microbiota alterations associated with reduced bone mineral density in older adults. Rheumatology (Oxford). 2019 Dec 1;58(12):2295-2304. doi: 10.1093/rheumatology/kez302.