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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06771050




Registration number
NCT06771050
Ethics application status
Date submitted
7/01/2025
Date registered
13/01/2025
Date last updated
13/01/2025

Titles & IDs
Public title
Randomised Arthroplasty Infection Worldwide Multidomain Adaptive Platform (ROADMAP) Trial is an International RCT Evaluating the Effect of a Range of Clinical Surgical and Antibiotic Interventions on Treatment Success 12 Mths Post-platform Entry in Adults With Prosthetic Joint Infection (PJI)
Scientific title
The RandOmised Arthroplasty Infection worlDwide Multidomain Adaptive Platform (ROADMAP) Trial
Secondary ID [1] 0 0
2024015- G2200907
Secondary ID [2] 0 0
R-2024-0041
Universal Trial Number (UTN)
Trial acronym
ROADMAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prosthetic Joint Infections of Hip 0 0
Prosthetic Joint Infections of Knee 0 0
Large Joint Prosthetic Joint Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Debridement and Implant Retention (DAIR)
Treatment: Drugs - Antibiotic Choice
Treatment: Drugs - Antibiotic duration Part A - Single stage revision
Treatment: Drugs - Antibiotic Duration Part B - Two stage revision

Active comparator: 1. SURGICAL DOMAIN: Late Acute Silo - Surgical Domain comparing outcomes of surgical strategies - Debridement and implant retention (DAIR) versus Revision arthroplasty (either one stage or two stage at the discretion of the treating surgeon)

Active comparator: 2. ANTIBIOTIC CHOICE DOMAIN - Backbone therapy alone (active comparator) versus Backbone antibiotic therapy plus Rifampicin.

Active comparator: 3. ANTIBIOTIC DURATION DOMAIN Part A - Single Stage Revision - Length of antibiotic course duration after a single stage revision, short course (6 weeks) versus long course (12 weeks).

Active comparator: 4. ANTIBIOTIC DURATION DOMAIN Part B - Two Stage Revision - No extended antibiotic prophylaxis versus extended antibiotic prophylaxis following a two-stage revision.


Treatment: Surgery: Debridement and Implant Retention (DAIR)
Intervention 1: DAIR- cleaning of infected joint including irrigation, debridement and exchange of modular components (those not fixed to bone) with implant retention.

Intervention 2: Single stage revision - cleaning of infected joint including irrigation, removal and placement of "definitive" new components which could be primary or revision components.

Treatment: Drugs: Antibiotic Choice
No intervention: Backbone antibiotic therapy only depends on the organism and is detailed in the protocol.

Intervention: Backbone antibiotic therapy plus rifampicin. Dosage 600-900mg per day orally for as long as oral antibiotic treatment continues, but not more than 12 weeks. Prescribed according to local recommended practices and dosed as per local therapeutic guidelines.

Treatment: Drugs: Antibiotic duration Part A - Single stage revision
Intervention Arm: Short course 6-week (42 +/- 7 days) antibiotic course - combined intravenous and oral with antibiotic choice according to organism and patient tolerability factors.

Intervention Arm: Long course 12- week (84 +/- 7 days) antibiotic course - combined intravenous and oral with antibiotic choice according to organism and patient tolerability factors.

Treatment: Drugs: Antibiotic Duration Part B - Two stage revision
Intervention Arm: Extended prophylaxis for 12 weeks after the 2nd stage revision surgery.

Intervention Arm: No extended antibiotic prophylaxis after the 2nd stage revision surgery.

Antibiotic choice by treating team with reference to the original causative organism(s), susceptibility and patient tolerability.
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment success at 12 months
Timepoint [1] 0 0
up to 13 months (with a window of up to 13 months i.e. 365 to 395 days) after platform entry.
Secondary outcome [1] 0 0
A "desirability of outcome ranking" DOOR
Timepoint [1] 0 0
Platform entry until day 265
Secondary outcome [2] 0 0
Patient-reported joint function (Oxford hip or knee score) at 12 months after platform entry.
Timepoint [2] 0 0
platform entry until day 365
Secondary outcome [3] 0 0
Patient-reported quality of life (EQ5D5L) at 12 months after platform entry.
Timepoint [3] 0 0
Platform entry until day 365
Secondary outcome [4] 0 0
Cost effectiveness over the first 12 months after platform entry.
Timepoint [4] 0 0
From platform entry until day 365
Secondary outcome [5] 0 0
All-cause mortality at 12 months after platform entry
Timepoint [5] 0 0
From platform entry until day 365
Secondary outcome [6] 0 0
"Clinical cure" at 12 months after platform entry (as defined in the primary outcome)
Timepoint [6] 0 0
From platform entry until day 365
Secondary outcome [7] 0 0
Proportion alive and no longer taking any antibiotics for the index joint at 12 months after platform entry (as defined in the primary outcome).
Timepoint [7] 0 0
From platform entry until day 365
Secondary outcome [8] 0 0
Proportion in whom the destination prosthesis is still in place at 12 months after platform entry (as defined in the primary outcome)
Timepoint [8] 0 0
From platform entry until day 365
Secondary outcome [9] 0 0
Microbiological relapse
Timepoint [9] 0 0
From platform entry until day 100 and day 365
Secondary outcome [10] 0 0
Microbiological reinfection
Timepoint [10] 0 0
From platform entry until day 100 and day 365
Secondary outcome [11] 0 0
Time alive and free from any revision procedure on the index joint captured by a national joint replacement registry within 24 months of platform entry
Timepoint [11] 0 0
From platform entry until 24 months

Eligibility
Key inclusion criteria
1. "Confirmed" or "Likely" Prosthetic joint infection of a large joint according to European Bone and Joint Infection Society (EBJIS) criteria (2021)
2. Physically present at participating hospital at time of eligibility assessment
3. "Current" prosthetic joint infection, meaning symptoms and/or signs of the PJI are present at the time of eligibility assessment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Potentially eligible participants meeting any of the following criteria at the time of eligibility assessment for platform entry will be excluded from the randomised platform (but may still participate in the registry):

1. The index prosthetic joint is a shoulder, elbow, wrist or ankle.
2. Known previous participation in the randomised ROADMAP randomised platform for the index joint.
3. Known previous participation in the randomised ROADMAP platform for a joint other than the index joint within the 12 months prior to eligibility assessment
4. Treating clinician believes that death is imminent and inevitable.
5. Treatment is not with curative intent.
6. Patient is not classifiable into one of the three defined silos.
7. Patient is unlikely to be accessible for follow up over the 12 months following platform entry.
8. Treating team deems enrolment in the study is not in the best interests of the patient.

To be included in any of the following Domains the participant must be eligible for the PLATFORM ( as listed above) and none of the platform-level exclusion criteria AND all of the domain-level inclusion and none of the domain-level exclusion criteria.

Domain-specific eligibility criteria Each domain may have additional criteria for eligibility. Participants who fulfil the above criteria will be assessed for enrolment into all domains active at a participating site. At least 2 interventions (which may include standard of care) within a domain must be available to an eligible participant in order for that participant to enter the domain. The minimum number of interventions within a domain is two. The availability of interventions within domains will be region- and site-specific, although the default position is that all interventions within a domain will be available at all sites.

Surgical Strategy Domain: Late Acute Silo inclusion criteria

Patient is in the Late Acute silo, meaning all of the following 3 criteria are met:

1. Onset of symptoms is >30 days after implantation of the index joint
2. Treating team feel that either DAIR or revision is appropriate for this patient.
3. The infected prosthesis is a primary arthroplasty. Surgical Strategy Domain: Late Acute Silo exclusion criteria

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1. Any previous episode of native joint septic arthritis or PJI in the index joint
2. A definitive DAIR has already occurred for this episode of infection.
3. A revision has already occurred for this episode of infection
4. Loosening or instability of any component of the prosthesis
5. Predicted inadequate soft tissue coverage for wound closure
6. One or more of the causative organisms is a fungus or a "difficult to treat" bacterium.
7. Treating team deems enrolment in this domain is not in the best interests of the patient.

Antibiotic Choice Domain inclusion criteria

1. The time of eligibility assessment is between 48h and 7 days following initial surgical treatment.
2. One or more of the causative organisms is a Gram-positive of interest OR the infection is culture negative.

Antibiotic Choice Domain exclusion criteria

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1. Previous hypersensitivity reaction to rifampicin
2. The patient is receiving a concomitant medication with an expected clinically significant drug interaction with rifampicin, which cannot be ceased, substituted for an alternative agent, or mitigated by dose adjustment.
3. One or more causative Gram-positive organisms of interest have in-vitro evidence of resistance to rifampicin
4. Known pregnancy or breastfeeding
5. Treating team deems enrolment in this domain is not in the best interests of the patient.

Antibiotic Duration Part A Domain inclusion criteria

1. A single stage revision procedure has been performed

For the purposes of this domain, the definition of a single stage revision procedure is as follows:

A one-stage revision means:

• Arthrotomy

• Removal of all prosthetic components

• Comprehensive synovectomy

• Placement of "definitive" new components
* could be primary or revision components • With no plans for a second stage operation

Additional recommended elements (not part of definition, but considered 'ideal' elements of this procedure):
* Removal of all loose cement; well-fixed cement may be retained.
* Double set up (using a separate set of sterile instruments and drapes for the reimplantation)

Antibiotic Duration Part A Domain exclusion criteria

Patients will be excluded from this domain if, at the time of eligibility assessment, they have any of the following:

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1. Any causative organism is a fungus or a 'difficult-to-treat' bacterium at the time of platform entry
2. Treating team deems enrolment in this domain is not in the best interests of the patient
3. The single stage revision was >7 days ago
4. Patient no longer willing to participate in the domain

Antibiotic Duration Part B Domain Eligibility assessment and allocation reveal will be performed at day 7 (+/- 3 days) from the time of the reimplantation operation - i.e. between 4 and 10 days following the reimplantation operation. The purpose of this time frame is to confirmation of negative reimplantation cultures.

Antibiotic Duration Part B Domain inclusion criteria

1. A two-stage revision procedure has been performed

For the purposes of this domain, the definition of two-stage revision and reimplantation procedures are defined as follows:

A two-stage revision means:

• Removal of all existing prosthetic components (including metal, ceramic, polyethylene) and any loose cement
* Placement of a temporary prosthesis or spacer with the intention to replace this at a later time point with a permanent prosthesis
* The intention to subsequently replace of the temporary spacer with a definitive prosthesis at a reimplantation operation in the future

Additional recommended elements (not part of definition, but encouraged):

• Use of antibiotic-loaded cement as the spacer
* Use of an articulating spacer which is capable of withstanding weight-bearing

A reimplantation procedure as the second stage of a two-stage revision means:

• Removal of the temporary prosthesis and all associated cement
* Implantation of a new prosthesis; considered the 'destination prosthesis'
2. The infected prosthesis was a primary (not revision) arthroplasty
3. At least 6 weeks of antibiotics have been received following the first stage revision, intended as treatment of the index infection
4. The reimplantation operation was done 4-10 days ago

Antibiotic Duration Part B Domain exclusion criteria

1. >6 months has passed since platform entry
2. One or more of the causative organisms is a fungus or a 'difficult-to-treat' bacterium
3. No perioperative tissue or fluid cultures were collected at the reimplantation operation
4. Perioperative cultures collected at reimplantation grow a significant organism (s)
5. Long-term antibiotic suppressive therapy is planned following the reimplantation operation
6. Treating team deems enrolment in this domain is not in the best interests of the patient
7. Patient no longer willing to participate in the domain

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
18/02/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
2500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA,AWA
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 0 0
St George - Kogarah
Recruitment hospital [6] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [8] 0 0
Mater Hospital Sydney ST Vincents Network - North Sydney
Recruitment hospital [9] 0 0
Westmead Hospital - Westmead
Recruitment hospital [10] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [11] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [12] 0 0
Townsville Hospital and Health Service - Douglas
Recruitment hospital [13] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [14] 0 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [15] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [16] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [17] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [18] 0 0
Calvary Adelaide Private Hospital - Adelaide
Recruitment hospital [19] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [20] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [21] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [22] 0 0
Eastern Health - Box Hill
Recruitment hospital [23] 0 0
Epworth Hospital - Box Hill
Recruitment hospital [24] 0 0
Dandenong/Monash Hospital - Dandenong
Recruitment hospital [25] 0 0
Northern health - Epping
Recruitment hospital [26] 0 0
St Vincents - Fitzroy
Recruitment hospital [27] 0 0
Western Health - Footscray
Recruitment hospital [28] 0 0
University Hospital Geelong - Geelong
Recruitment hospital [29] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [30] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [31] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
2747 - Camperdown
Recruitment postcode(s) [4] 0 0
2747 - Kingswood
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
2170 - Liverpool
Recruitment postcode(s) [7] 0 0
2305 - New Lambton
Recruitment postcode(s) [8] 0 0
2060 - North Sydney
Recruitment postcode(s) [9] 0 0
2145 - Westmead
Recruitment postcode(s) [10] 0 0
4575 - Birtinya
Recruitment postcode(s) [11] 0 0
4032 - Chermside
Recruitment postcode(s) [12] 0 0
4814 - Douglas
Recruitment postcode(s) [13] 0 0
4029 - Herston
Recruitment postcode(s) [14] 0 0
4020 - Redcliffe
Recruitment postcode(s) [15] 0 0
4101 - South Brisbane
Recruitment postcode(s) [16] 0 0
4215 - Southport
Recruitment postcode(s) [17] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [18] 0 0
5000 - Adelaide
Recruitment postcode(s) [19] 0 0
5011 - Adelaide
Recruitment postcode(s) [20] 0 0
5042 - Bedford Park
Recruitment postcode(s) [21] 0 0
5011 - Woodville
Recruitment postcode(s) [22] 0 0
3128 - Box Hill
Recruitment postcode(s) [23] 0 0
3175 - Dandenong
Recruitment postcode(s) [24] 0 0
3076 - Epping
Recruitment postcode(s) [25] 0 0
3065 - Fitzroy
Recruitment postcode(s) [26] 0 0
3011 - Footscray
Recruitment postcode(s) [27] 0 0
3220 - Geelong
Recruitment postcode(s) [28] 0 0
3011 - Melbourne
Recruitment postcode(s) [29] 0 0
6150 - Murdoch
Recruitment postcode(s) [30] 0 0
6000 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
University of Newcastle, Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Hunter Medical Research Institute (HMRI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The University of Western Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Michael Garron Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Aotearoa Clinical Trials
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Exeter Orthopaedic Trial unit
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
University of Sydney
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
University of Melbourne
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
The Peter Doherty Institute for Infection and Immunity
Address [8] 0 0
Country [8] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Artificial joint infections are treated with different types of antibiotics and surgery. The ROADMAP study aims to find out which treatments currently used work best in regards to surgery, antibiotic choice as well as the time taking antibiotics. The study will compare different treatments against each other to see which treatment or treatment combination works to provide the best outcome and cure at 12 months. The study will focus on adults with infected artificial hips and knees.

ROADMAP trial looks at normal good clinical care and does not ask any person taking part in the study to have any extra tests or treatments.

If a person takes part in the study they will:

* Sign a consent form
* Give permission for infection and treatment information to be collected and entered into a central ROADMAP specific database and a separate registry of prosthetic joint infection patients. This medical information will include participants medical history, test results and treatment they received. The study will also collect information about medical care and how the participant is feeling at Day 100 and Day 365 (1 year) after starting the study.

There are several different study parts. Each part focuses on research focus areas called domains. ROADMAP has 3 different domains; 1. Surgical, 2. Antibiotic choice and 3. Antibiotic Duration domains. Not every hospital is taking part in all 3 domains and if someone chooses to participate they do not have to participate in all domains. Specific domain details are:

1. Surgical Treatment Domain This domain will find out if it is better to do an operation to clean out the infection but keep the artificial joint in place (this is called a Debridement, Antibiotics and Implant Retention operation (DAIR)) or to clean out the infection and swap your artificial joint out for a new one (this is called a "revision" operation).

DAIR usually involves a single operation but sometimes needs more. Revision surgery may be done in one operation (single stage revision) or two operations (two stage revision). Previous research has suggested that cure rates may be better with revision operations than with DAIR, but this is not clear.

If the participant consents to the surgical domain they will be randomly allocated to either a DAIR, to clean the artificial joint but keep it in place, or to have surgery that cleans and replaces the artificial joint with a new one (revision). A revision operation, may involve one (single stage) or two different surgeries which can be days, weeks or months apart (two stage).

The participants surgeon and treating team in consultation with the participant will decide what kind of treatment they are best to receive, DAIR, single stage or two stage revision.
2. Antibiotic Choice Domain Many different microorganisms (germs) can cause artificial joint infections and many different antibiotics are used to fight infections. ROADMAP will look at different antibiotics commonly used to treat artificial joint infection. This domain will focus on an antibiotic called rifampicin (also sometimes known as rifampin) as it is often added to other antibiotics to help treat artificial joint infections. Rifampicin is not a new antibiotic but it is not clear if treatment cure rates are better if it is added.

All people taking part in this domain will be given antibiotics that will treat their artificial joint infection, called the "backbone antibiotics", but some will be given "backbone antibiotics" plus rifampicin. "Backbone antibiotics" can be either one antibiotic or a number of different antibiotics. These will be given into a vein (IV) at first, and will be changed to tablets or capsules later.

All antibiotics in this domain are commonly used and the "backbone antibiotics" will be chosen by treating doctors after looking at the type of germ and what antibiotic may work for the germ, as well as medical history including past antibiotic reactions. Antibiotics are taken for approximately 12 weeks after DAIR surgery, however after revision surgery then the time taking antibiotics may be shorter or longer.
3. Antibiotic Duration Domain Antibiotic treatment times are the focus of this domain as it is not clear how long someone should take antibiotics when revision surgery is used to treat artificial joint infection. To show what antibiotic time period is best for treatment and cure people who have had revision surgery participating in this domain will receive either "standard" or "extended" duration of antibiotics.

In this domain, after a one-stage revision, the participant will be randomised to have either 6 weeks or 12 weeks of antibiotics after the operation. If a two-stage revision operation has been done the participant will receive around 6 weeks of antibiotics between the two operation stages. After the two stage revision has been completed the participant will be randomised to either stop antibiotics or have a further 12 weeks of antibiotic treatment.
Trial website
https://clinicaltrials.gov/study/NCT06771050
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joshua S Davis. Co-chief Investigator, infectious diseases Specialist
Address 0 0
University of Newcastle, Menzies Institute, Hunter Medical Research Institute, Hunter New England Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Joshua S Davis, Chief Investigator
Address 0 0
Country 0 0
Phone 0 0
61240420994
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06771050