Antibiotic Loaded Bone Cement in Prevention of Periprosthetic Joint Infections in Primary Total Knee Arthroplasty

NCT04135170 | Unknown Phase 2

• 1 other identifier: NorwegianArthroplastyRegister
• Study Type: interventional
• Target: 9,172
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: The current evidence on the efficacy of Antibiotic Loaded Bone Cement (ALBC) in reducing the risk of periprosthetic joint infections (PJI) after primary joint reconstruction is insufficient. In several European countries, the use of ALBC is routine practice unlike in the US where ALBC use is not approved in low-risk patients. It has been claimed that the antibiotic in ALBC increase the risk of aseptic loosening, risk of systemic toxicity, allergic reaction, and bacterial resistance. Therefore we designed a double-blinded (patients and data analysts) pragmatic multicenter register-based randomized controlled non-inferiority trial to investigate the effects of ALBC compared to plain bone cement in primary total knee arthroplasty (TKA). Methods and analysis: A minimum of 9,172 patients undergoing full-cemented primary TKA will be recruited and equally randomized into the ALBC group and the plain bone cement group. This trial will be conducted in Norwegian hospitals that routinely perform cemented primary TKA. . The primary outcome will be risk of revision surgery due to PJI at 1-year of follow-up. Secondary outcomes will be:

• risk of revision due to any reason including aseptic loosening at 1-, 6-, 10-, and 20-years of follow-up;
• patient related outcome measures (PROMs) like function, pain, satisfaction, and health-related quality of life at 1-, 6-, and 10-years of follow-up;
• risk of changes in the microbial pattern and resistance profiles of organisms cultured in subsequent revisions at 1-, 6-, 10-, and 20-years of follow-up; and
• cost-effectiveness of routine ALBC vs plain bone cement use in primary TKA. We will use 1:1 randomization with random permuted blocks and stratify by participating hospitals to randomize patients to receive ALBC or plain bone cement. Inclusion, randomization, and follow-up will be through the Norwegian Arthroplasty Register. Ethics and dissemination: The trial has been approved by the Western Norway Regional Committees on Medical and Health Research Ethics (REK-Vest) (reference number: 2019/751/REK vest) dated: 21.06.2019. The trial results will be reported following the Consolidated Standards of Reporting Trials Extension (CONSORT Extension) reporting guideline 2010 statement for non-inferiority trials. The trial results will be reported to the public through national and international scientific conferences, participating hospitals, patient organizations, and peer-reviewed journals. Discussion: If we find that plain bone cement is non-inferior to the ALBC, it will challenge the routine use of ALBC in primary arthroplasty, due to ecological concerns and costs. However, if routine use of ALBC is associated with a reduced risk of PJI and with minor impact on bacterial resistance, PROMs, and costs, the well-established use of prophylactic ALBC in primary arthroplasty will be supported

Conditions

Osteoarthritis, Knee

Keywords

Register based randomized control trial; Non-inferiority; Total knee arthroplasty; Antibiotic loaded bone cement; Plain bone cement; Antibiotic resistance bacteria; Periprosthetic joint infection; Patient reported outcome measure; Health related quality of life; Pain; Function; Satisfaction; Revision surgery; Primary surgery

Outcome Measures

Primary Outcomes (1)

• risk of revision due to PJI

  1-year follow-up

Secondary Outcomes (6)

• risk of revision due to any reason including aseptic loosening

  1-, 6-, 10-, and 20-years follow-up

• risk of changes in the microbial pattern and resistance profiles of organisms cultured in subsequent revisions

  1-, 6-, 10-, and 20-years follow-up

• Change in mean scores from baseline function (in activity of daily life) on the Knee injury and Osteoarthritis Outcome Score (KOOS).

  1-, 6-, and 10-years follow-up

• Change in mean scores from baselinein in Visual Analog Sale (the scores range from 0 to 100, with 0 indicating the worst possible state and 100 indicating the best possible state) for pain.

  1-, 6-, and 10-years follow-up

• Change in mean scores from baseline in EQ-5D-5L for health related quality of life(HRQoL).

  1-, 6-, and 10-years follow-up

Study Arms (2)

Plain bone cement

EXPERIMENTAL

Combination Product: ALBC vs plain bone cement

Antibiotic loaded bone cement

ACTIVE COMPARATOR

Combination Product: ALBC vs plain bone cement

Interventions

ALBC vs plain bone cement COMBINATION_PRODUCT

The patients undergoing full-cemented primary total knee arthroplasty are allocated to either ALBC or plain bone cement and compare the effectiveness of ALBC use vs pain bone cement bone cement without antibiotic) with respect to revision due to PJI one year after primary TKA surgery.

Antibiotic loaded bone cement; Plain bone cement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• all patients undergoing full-cemented primary TKA irrespective of the diagnosis leading to TKA

Sponsors & Collaborators

• The Norwegian Arthroplasty Register: lead
• Helse Vest: collaborator

Study Sites (1)

Department of Orthopeadic Surgery, Haukeland University Hospital

Bergen, Norway

RECRUITING

Related Publications (1)

• Leta TH, Gjertsen JE, Dale H, Hallan G, Lygre SHL, Fenstad AM, Dyrhovden GS, Westberg M, Wik TS, Jakobsen RB, Aamodt A, Rohrl SM, Gothesen OJ, Lindalen E, Heir S, Ludvigsen J, Bruun T, Hansen AK, Aune KEM, Warholm M, Skjetne JP, Badawy M, Hovding P, Husby OS, Karlsen OE, Furnes O. Antibiotic-Loaded Bone Cement in Prevention of Periprosthetic Joint Infections in Primary Total Knee Arthroplasty: A Register-based Multicentre Randomised Controlled Non-inferiority Trial (ALBA trial). BMJ Open. 2021 Jan 28;11(1):e041096. doi: 10.1136/bmjopen-2020-041096.

  PMID: 33509845 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain; Personal Satisfaction

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Ove Furnes, MD/PhD

  The Norwegian Arthroplasty Register, Department of Orthopedic Surgery, Haukeland University Hospital

  STUDY CHAIR

Central Study Contacts

Tesfaye H Leta, PhD

CONTACT

+4791691925; tesfaye.hordofa.leta@helse-bergen.no

Ove Furnes, MD/PhD

CONTACT

+4790840088; ove.nord.furnes@helse-bergen.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: This is a double blinded, non-inferiority register-based multicenter randomized controlled trial study. To ensure blinding of the patients, all patients are operated by the same surgical method and the type of cement is unknown to the patients. In this study, blinding of the surgeon is not possible because the surgeon recognizes the cement type and has to document the type of cement in the registration form. We believe the primary endpoint of this trial is not likely to be influenced by the surgeon knowledge of the cement used in the index surgery. The data analyst will be blinded for groups until the entire trial analysis has been completed to minimize the risk of bias that may be introduced during the statistical analysis because of the selective use and reporting of statistical tests.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor/ postdoc fellowship

Model Details: Patients undergoing full-cemented primary TKA in any Norwegian hospitals are eligible for participation irrespectively of the diagnosis leading to TKA. and randomly assigned to receive ALBC (control group) or plain bone cement (experimental group).

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: October 22, 2019
• Study Start: January 14, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2025
• Last Updated: January 19, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)