ROADMAP Clinical Trial (NCT06771050) — Australia Trial Details

Condition(s) studied

Prosthetic Joint Infections of HipProsthetic Joint Infections of KneeLarge Joint Prosthetic Joint Infections

Investigational drug(s) / intervention(s)

Debridement and Implant Retention (DAIR)Antibiotic ChoiceAntibiotic duration Part A - Single stage revisionAntibiotic Duration Part B - Two stage revision

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.

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.

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.

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.

Study 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 the 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

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. 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  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  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:  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

Primary outcome measure(s)

Treatment success at 12 months — up to 13 months (with a window of up to 13 months i.e. 365 to 395 days) after platform entry.
The primary endpoint for all cells and domains will be treatment success at 12 months, defined as ALL FOUR OF: 1. Patient is alive. 2. Clinical cure = no clinical or microbiological evidence of ongoing infection in the index joint 3. The patient is no longer taking antibiotics for the index joint. 4. The destination prosthesis is still in place. The primary endpoint is determined through a search of hospital databases for a record of participant's death, or follow-up contact with participant's community healthcare provider, or follow-up contact with patient or their nominated carer, or linkage with death registries. The preferred method is through direct face to face clinic visit. However, phone contact with the patient may occur. In addition, any or all of the four components of the primary endpoint can be derived from external data such as GP records or specialist letters.

Trial sites (43)

Facility	City	Region	Status
The Canberra Hospital	Garran	Australian Capital Territory	Not Yet Recruiting
Bankstown- Lidcombe Hospital	Bankstown	New South Wales	Not Yet Recruiting
Blacktown Hospital	Blacktown	New South Wales	Recruiting
Campbelltown Hospital	Campbelltown	New South Wales	Recruiting
Royal Prince Alfred Hospital	Camperdown	New South Wales	Recruiting
Sutherland Hospital	Caringbah	New South Wales	Recruiting
Ramsay Research C/O Lake Macquarie Private Hospital	Gateshead	New South Wales	Recruiting
Nepean Hospital	Kingswood	New South Wales	Recruiting
St George	Kogarah	New South Wales	Recruiting
Liverpool Hospital	Liverpool	New South Wales	Recruiting
John Hunter Hospital	New Lambton	New South Wales	Recruiting
Mater Hospital Sydney ST Vincents Network	North Sydney	New South Wales	Not Yet Recruiting
Prince of Wales Hospital	Randwick	New South Wales	Recruiting
Westmead Hospital	Westmead	New South Wales	Recruiting
Logan Beaudesert Hospital	Beaudesert	Queensland	Recruiting
Sunshine Coast University Hospital	Birtinya	Queensland	Not Yet Recruiting
Prince Charles Hospital	Chermside	Queensland	Not Yet Recruiting
Townsville Hospital and Health Service	Douglas	Queensland	Not Yet Recruiting
Royal Brisbane and Women's Hospital	Herston	Queensland	Recruiting
Redcliffe Hospital	Redcliffe	Queensland	Not Yet Recruiting
Mater Hospital Brisbane	South Brisbane	Queensland	Recruiting
Gold Coast University Hospital	Southport	Queensland	Recruiting
Toowoomba Hospital- Darling Downs Health	Toowoomba	Queensland	Recruiting
Princess Alexandra Hospital	Woolloongabba	Queensland	Recruiting
Calvary Adelaide Private Hospital	Adelaide	South Australia	Recruiting
Royal Adelaide Hospital	Adelaide	South Australia	Recruiting
Flinders Medical Centre	Bedford Park	South Australia	Recruiting
The Queen Elizabeth Hospital	Woodville	South Australia	Recruiting
Launceston General Hospital	Launceston	Tasmania	Not Yet Recruiting
Eastern Health	Box Hill	Victoria	Recruiting
Dandenong/Monash Hospital	Dandenong	Victoria	Not Yet Recruiting
Northern health	Epping	Victoria	Recruiting
St Vincents	Fitzroy	Victoria	Recruiting
Western Health	Footscray	Victoria	Recruiting
University Hospital Geelong	Geelong	Victoria	Not Yet Recruiting
The Alfred Hospital	Melbourne	Victoria	Recruiting
Latrobe Regional Hospital	Traralgon	Victoria	Recruiting
Sir Charles Gairdner Hospital	Nedlands	Western Australia	Recruiting
Royal Perth Hospital	Perth	Western Australia	Recruiting
Fiona Stanley Hospital	Murdoch	Western AustraliaA	Recruiting

+ 3 more sites — see the full list on the official registry below.

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