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

Antibiotic Loaded Bone Cement in Prevention of Periprosthetic Joint Infections in Primary Total Knee Arthroplasty: A Register-based Multicenter Randomized Controlled Non-inferiority Trial (Acronym: ALBA Trial)

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

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Combination product: ALBC vs plain bone cement

• Study Type: Interventional
• Enrollment (Anticipated): 9172
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tesfaye H Leta, PhD; Phone Number: +4791691925; Email: tesfaye.hordofa.leta@helse-bergen.no
• Study Contact Backup: Name: Ove Furnes, MD/PhD; Phone Number: +4790840088; Email: ove.nord.furnes@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway
    • Recruiting
    • Department of Orthopeadic Surgery, Haukeland University Hospital
    • Contact: Ove Furnes, PhD; Phone Number: 0047 55975690; Email: ove.nord.furnes@helse-bergen.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• any history of infection in the knee, a need for fully stabilized or hinged TKA, a history of allergy to the antibiotics used in the cement, inability or not willing to consent for inclusion in NAR or the trial, and participation in other studies that might have pharmacological interaction with this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plain bone cement	Combination product: ALBC vs plain bone cement; 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.
Active Comparator: Antibiotic loaded bone cement	Combination product: ALBC vs plain bone cement; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
risk of revision due to PJI	1-year follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Mean scores 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 patient satisfaction.	1-, 6-, and 10-years follow-up

Collaborators and Investigators

• Sponsor: The Norwegian Arthroplasty Register
• Collaborators: Helse Vest
• Investigators: Study Chair: Ove Furnes, MD/PhD, The Norwegian Arthroplasty Register, Department of Orthopedic Surgery, Haukeland University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: October 20, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pain; Satisfaction; Total knee arthroplasty; Function; Health related quality of life; Non-inferiority; Patient reported outcome measure; Revision surgery; Register based randomized control trial; Antibiotic loaded bone cement; Plain bone cement; Antibiotic resistance bacteria; Periprosthetic joint infection; Primary surgery
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Infections
• Other Study ID Numbers: NorwegianArthroplastyRegister

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No