Clinical trial NCT04135170: Antibiotic Loaded Bone Cement in Prevention of Periprosthetic Joint Infections in Primary Total Knee Arthroplasty
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: The Norwegian Arthroplasty Register
Sponsor class: OTHER_GOV
Collaborators: name: Helse Vest
First posted: 2019-10-22
Enrollment: 9172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: PREVENTION

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


Eligibility criteria: 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.

Primary outcomes:
measure: risk of revision due to PJI
timeFrame: 1-year follow-up
Secondary outcomes:
measure: risk of revision due to any reason including aseptic loosening
timeFrame: 1-, 6-, 10-, and 20-years follow-up
measure: risk of changes in the microbial pattern and resistance profiles of organisms cultured in subsequent revisions
timeFrame: 1-, 6-, 10-, and 20-years follow-up
measure: Change in mean scores from baseline function (in activity of daily life) on the Knee injury and Osteoarthritis Outcome Score (KOOS).
timeFrame: 1-, 6-, and 10-years follow-up
measure: 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.
timeFrame: 1-, 6-, and 10-years follow-up
measure: Change in mean scores from baseline in EQ-5D-5L for health related quality of life(HRQoL).
timeFrame: 1-, 6-, and 10-years follow-up
measure: 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.
timeFrame: 1-, 6-, and 10-years follow-up
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Department of Orthopeadic Surgery, Haukeland University Hospital
Study officials:
affiliation: The Norwegian Arthroplasty Register, Department of Orthopedic Surgery, Haukeland University Hospital
name: Ove Furnes, MD/PhD
role: STUDY_CHAIR
References:
citation: 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.