Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001357549
Ethics application status
Approved
Date submitted
17/11/2015
Date registered
15/12/2015
Date last updated
9/06/2021
Date data sharing statement initially provided
9/06/2021
Date results provided
9/06/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Prosthetic Joint Infection in Australia and New Zealand Observational
(PIANO) Study
Scientific title
Prosthetic Joint Infection in Australia and New Zealand Observational
(PIANO) Study
Secondary ID [1] 287777 0
None
Universal Trial Number (UTN)
Trial acronym
PIANO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prosthetic Joint Infection 296668 0
Condition category
Condition code
Infection 296889 296889 0 0
Other infectious diseases
Public Health 297086 297086 0 0
Epidemiology

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The objective of the PIANO study is to describe prospectively in detail the clinical, laboratory, microbiological and radiological features, economic costs for patients presenting with prothetic joint infection and treatment outcomes in terms of initial treatment strategy, surgical methods, choice and duration of antibiotic therapy and micro-organism (duration of 5.75 years in total, May 2014-Dec 2019).
Intervention code [1] 293170 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296493 0
Infection outcomes will measure the number of patients with clinical cure & relapse free prosthesis survival.
Clinical cure is defined as those who remain alive, with no clinical evidence of ongoing infection timed from the day of diagnosis. At 12 month and 24 month cure will be defined as all four of:
i. No clinical evidence of infection (none of the following: draining fistula; redness, swelling or effusion of the index joint, fever without alternative explanation)
ii. No microbiological evidence of infection (as per inclusion criteria, but does not have to be with the initial infecting organism).
iii. No use of ongoing antibiotic therapy for the index joint infection.
& Relapse-free prosthesis survival defined as patients who are judged to have been clinically cured at the end of the initial management, the subsequent time that the prosthesis remains in place and free of relapse. Relapse will be defined as either
i) Clinical relapse – any of the above mentioned 3 criteria.
ii) Microbiological relapse – growth of one or more of the originally infecting pathogens from either synovial fluid or intra-operative fluid or tissue specimens.
Timepoint [1] 296493 0
This will be defined at 12 month and 24 months from the day of diagnosis of prosthetic joint infection.
Primary outcome [2] 296690 0
Cost outcomes will be calculated from the health payer perspective and will be extrapolated to estimate the total annual national cost.
Primary data collected to inform cost analysis will be length of hospital stay, number and nature of operating theatre visits; nature of any new prosthesis inserted in the 12-month period; use of pathology and radiology services, length of “hospital in the home” treatment and direct antibiotic costs. Costs attributable to hospitalisation will be based on data from each participating institution. Outpatient costs will be derived from medicare rebates, whilst drug costs will estimated from listed drug costs from Pharmaceutical Benefits Scheme (PBS), or in the case of rifampicin and other non-PBS drugs, from direct pharmacy costs.
Timepoint [2] 296690 0
The direct annual costs of PJI to the Australian health care system will be estimated using costs incurred over the first 12 months post diagnosis.
Secondary outcome [1] 319130 0
Functional outcomes will measure the impact of the prosthetic joint infection on the individual. This will be determined by;
i. The Oxford Hip and Knee score, a disease- specific, short, patient-centred questionnaire that is designed to assess functional ability and pain from the patient's perspective and.
ii. The Short Form-12 Health Survey (SF-12 v2.0) which provides a comprehensive, psychometrically sound, and efficient way to measure health from the patient's point of view by scoring responses to standardised questions.
Timepoint [1] 319130 0
This will be will be assessed at 3, 12, and 24 months after diagnosis of prosthetic joint infection.

Eligibility
Key inclusion criteria
a. Age at least 18 years
b. Prosthetic Joint infection diagnosed according to infection clinically suspected by an infectious diseases specialist or orthopaedic surgeon, AND presence of at least one of:
i. Presence of sinus tract communicating with the prosthesis
ii. Increased leukocyte count or neutrophil percentage in preoperative synovial fluid aspirate (synovial fluid white blood cell count over 1700 cells/microlitre or neutrophil percentage greater than 65%).
iii. Visible pus around the prosthesis at operation without alternative explanation
iv. Acute inflammation as reported by the clinical pathologist on examination of periprosthetic tissue (>=5 or more neutrophils per high power field)
v. Two or more pre-operative or intraoperative cultures (blood, synovial fluid, peri-prosthetic tissue, or sonication fluid) that yield the same organism (indistinguishable based on common laboratory tests including genus and species identification or common antibiogram).
vi. Pure growth of Staphylococcus aureus, beta-haemolytic streptococci or pathogenic aerobic Gram negative rod from a single synovial fluid or intraoperative tissue/fluid specimen
Adapted from Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA 2012)15, and Guideline on The Diagnosis of Periprosthetic Joint Infections of the Hip and Knee (AAOS 2010)16
c. The infected joint is one of hip, knee, shoulder, elbow, wrist or ankle
d. The infected prosthesis is either a total joint replacement or hemi-arthroplasty.
e. The PJI is “current”. This means that there is ongoing active treatment for it at the time of enrollment, and that all data relating to this episode are accessible. For example if the infection was diagnosed at another hospital 3 months ago, and is currently being treated at the recruiting site, then they can be enrolled as long as the data from the original hospital are accessible.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Unable to give informed consent
b. Infected hardware other than intra-articular prostheses (this includes pins and plates, screws, nails and wires) – unless there is a concomitant intra-articular prosthesis infection.
c. Unlikely to be accessible for follow up over next 24 months – any one of:
a. Ordinarily lives outside of Australia and New Zealand
b. Has no access to landline or mobile telephone
d. Relapse of previous infection
Since the primary mode of analysis is survival analysis, participants will not be excluded on the basis of being unlikely to survive for any particular period of time.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Depending on the type of data, the demographic results will be expressed as mean +/- SD or number of subjects (percentage).
‘Cure’ will be used as a dichotomous dependent variable in a logistic regression analysis. Variables such as infecting organism, initial management strategy, age, weight, co-morbidities will be included in a backward stepwise progression. The most parsimonious model will be determined using AIC and ANOVA methods. The sample size and the expected rates of cure will enable incorporation of between 5-10 variables safely in the final models
Subgroup analyses will also be performed for initial management strategy and infecting microorganism. A number of variables will be evaluated with regards to treatment outcome within the following parameters: (i) type of joint prosthesis, (ii) type of surgical procedure, (iii) type of antimicrobial treatment.
Factors that influence the functional status of participants will be identified by a bivariate survival analysis (Kaplan-Meier). Potential risk factors identified will be then confirmed by a multivariate survival analysis (Cox regression model). The results are expressed as hazard ratios with 95% confidence intervals.
Size of study population;
In total, we expect to recruit >600 (150-300/y) patients, making this one of the largest and most detailed prospective observational studies of PJIs in the world. These case-numbers are feasible; at the 5 initial pilot sites, we estimate that 75-100 patients per year can be recruited including 25-30, 20-25, 15-25, 10-20 and 5-10 patients from Fremantle, Royal Perth, St. Vincent’s, John Hunter and Brisbane Private hospitals, respectively. Based on data from the workload study from the workload study, =20 sites in Australia and =5 sites in NZ will enrol patients into this study. This will ensure collection of data that captures the heterogeneity of management approaches from a broad cross-section of centres across Australia and NZ.
This sample size provides adequate statistical power to answer important questions. For example, 300 patients will provide 80% power (at a significance level of 5%) to detect a difference in cure rates at 24 months of 10% (80% versus 70%) in two treatment groups. Within this framework, the following key research questions can be addressed to inform the design of subsequent randomised controlled trials: i) do patients who do not meet the conventional requirements for DAIR, but have this initial approach, have poorer outcomes than initial 2-stage replacement strategy, ii) do patients that undergo DAIR and treated with rifampicin have superior 24-month cure rates than those who are not and iii) if rifampicin is part of the antibiotic regimen, is the duration of intravenous antibiotics (dichotomised as =2 versus >2 weeks,) an important predictor of clinical cure?

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/06/2014
Date of last participant enrolment
Anticipated
31/12/2017
Actual
31/12/2017
Date of last data collection
Anticipated
Actual
31/12/2019
Sample size
Target
600
Accrual to date
Final
783
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 4539 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [2] 4540 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [3] 4541 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 4542 0
St John of God Hospital, Murdoch - Murdoch
Recruitment hospital [5] 4543 0
St Andrew's War Memorial Hospital - Brisbane
Recruitment hospital [6] 4544 0
Brisbane Private Hospital - Brisbane
Recruitment hospital [7] 4545 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [8] 4546 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [9] 4547 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [10] 4548 0
Wollongong Hospital - Wollongong
Recruitment hospital [11] 4550 0
Nepean Hospital - Kingswood
Recruitment hospital [12] 4551 0
The Northern Hospital - Epping
Recruitment hospital [13] 4552 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [14] 4553 0
Royal Hobart Hospital - Hobart
Recruitment hospital [15] 4554 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [16] 4555 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment hospital [17] 4556 0
Logan Hospital - Meadowbrook
Recruitment hospital [18] 4557 0
Prince of Wales Hospital - Randwick
Recruitment hospital [19] 7250 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [20] 7251 0
Calvary Wakefield Hospital - Adelaide
Recruitment hospital [21] 7252 0
Calvary North Adelaide Hospital - North Adelaide
Recruitment hospital [22] 7253 0
The Burnside War Memorial Hospital - Toorak Gardens
Recruitment hospital [23] 7254 0
Holy Spirit Northside - Chermside
Recruitment hospital [24] 7255 0
The Canberra Hospital - Garran
Recruitment hospital [25] 7256 0
Dandenong Hospital - Dandenong
Recruitment hospital [26] 7257 0
Latrobe Regional Hospital - Traralgon
Recruitment postcode(s) [1] 12156 0
6160 - Fremantle
Recruitment postcode(s) [2] 12157 0
6150 - Murdoch
Recruitment postcode(s) [3] 12158 0
4001 - Brisbane
Recruitment postcode(s) [4] 12159 0
4000 - Brisbane
Recruitment postcode(s) [5] 12161 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [6] 12162 0
4020 - Redcliffe
Recruitment postcode(s) [7] 12163 0
2305 - New Lambton Heights
Recruitment postcode(s) [8] 12164 0
2500 - Wollongong
Recruitment postcode(s) [9] 12165 0
2031 - Randwick
Recruitment postcode(s) [10] 12166 0
2747 - Kingswood
Recruitment postcode(s) [11] 12167 0
3076 - Epping
Recruitment postcode(s) [12] 12168 0
3220 - Geelong
Recruitment postcode(s) [13] 12169 0
7000 - Hobart
Recruitment postcode(s) [14] 12170 0
4102 - Woolloongabba
Recruitment postcode(s) [15] 12171 0
4108 - Coopers Plains
Recruitment postcode(s) [16] 12172 0
4131 - Meadowbrook
Recruitment postcode(s) [17] 12173 0
3175 - Dandenong
Recruitment postcode(s) [18] 12174 0
3844 - Traralgon
Recruitment postcode(s) [19] 15019 0
5011 - Woodville
Recruitment postcode(s) [20] 15020 0
5000 - Adelaide
Recruitment postcode(s) [21] 15021 0
5006 - North Adelaide
Recruitment postcode(s) [22] 15022 0
5065 - Toorak Gardens
Recruitment postcode(s) [23] 15023 0
4032 - Chermside
Recruitment postcode(s) [24] 15024 0
2605 - Garran
Recruitment outside Australia
Country [1] 7289 0
New Zealand
State/province [1] 7289 0

Funding & Sponsors
Funding source category [1] 292312 0
Charities/Societies/Foundations
Name [1] 292312 0
John Hunter Hospital Charitable Trust
Country [1] 292312 0
Australia
Funding source category [2] 292353 0
Commercial sector/Industry
Name [2] 292353 0
Heraeus Medical Australia
Country [2] 292353 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Society for Infectious Diseases Clinical Research Network
Address
Suite 701, Level 7,46-56 Kippax Street
Surry Hills NSW 2010
Australia
Country
Australia
Secondary sponsor category [1] 291032 0
None
Name [1] 291032 0
None
Address [1] 291032 0
None
Country [1] 291032 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293817 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 293817 0
Ethics committee country [1] 293817 0
Australia
Date submitted for ethics approval [1] 293817 0
09/04/2014
Approval date [1] 293817 0
05/05/2014
Ethics approval number [1] 293817 0
HREC/14/HNE/120

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61302 0
Dr Joshua Davis
Address 61302 0
Immunology & Infectious Diseases Department
John Hunter Hospital
Lookout Rd, New Lambton Heights NSW 2305
Country 61302 0
Australia
Phone 61302 0
+61 2 4921 3000
Fax 61302 0
+61 2 4922 3428
Email 61302 0
[email protected]
Contact person for public queries
Name 61303 0
Laurens Manning
Address 61303 0
University of Western Australia
Harry Perkins research Institute
Fiona Stanley Hospital
PO Box 404
Bull Creek WA 6149
Country 61303 0
Australia
Phone 61303 0
+61 8 61511156
Fax 61303 0
+61 8 61511199
Email 61303 0
[email protected]
Contact person for scientific queries
Name 61304 0
Joshua Davis
Address 61304 0
Immunology & Infectious Diseases Department
John Hunter Hospital
Lookout Rd, New Lambton Heights NSW 2305
Country 61304 0
Australia
Phone 61304 0
+61 2 4921 3000
Fax 61304 0
+61 2 4922 3428
Email 61304 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseClinical Characteristics, Etiology, and Initial Management Strategy of Newly Diagnosed Periprosthetic Joint Infection: A Multicenter, Prospective Observational Cohort Study of 783 Patients.2020https://dx.doi.org/10.1093/OFID/OFAA068
EmbasePredictors of Treatment Success after Periprosthetic Joint Infection: 24-Month Follow up from a Multicenter Prospective Observational Cohort Study of 653 Patients.2022https://dx.doi.org/10.1093/ofid/ofac048
N.B. These documents automatically identified may not have been verified by the study sponsor.