Ignite Creation Date:
2025-12-24 @ 5:10 PM
Ignite Modification Date:
2025-12-24 @ 5:10 PM
Study NCT ID:
NCT06771050
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-03-10
First Post:
2025-01-07
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Randomised Arthroplasty Infection Worldwide Multidomain Adaptive Platform (ROADMAP) Trial
Sponsor:
University of Newcastle, Australia
Organization:
Study Overview
Official Title:
The RandOmised Arthroplasty Infection worlDwide Multidomain Adaptive Platform (ROADMAP) Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ROADMAP
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 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.
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.
Detailed Description:
Over 120,000 hip or knee replacements are performed in Australia every year, and there are \~1 million Australians living with one or more joint replacements. Approximately 3,900 prosthetic joint infections (PJI) are diagnosed in Australia every year. The burden is similar in other resource-rich countries. For example, in Canada, over 130,000 hip and knee replacements are performed yearly and 2% of primary arthroplasties require a revision within 2 years. Infection has been identified as the most common cause for a revision surgery, which translates to $42.1 million CAD in inpatient costs to the Canadian health care system.
PJIs are difficult to treat, because of the presence of a foreign body, which encourages biofilm formation, and the need for combined surgical and prolonged antibiotic management. Outcomes are generally poor, with substantial variation in reported treatment success (ranging from 10 to 90%, median 50% after 2 years) and PJIs have striking health care costs. Existing treatment guidelines are informed by low quality evidence, with fewer than 1,700 participants ever enrolled into published randomised controlled trials comparing management approaches. Defining the optimal surgical and antibiotic approaches to PJI is a critical unmet need.
The Investigators are using an adaptive platform trial to allow the investigators to simultaneously address these questions in the management of PJI. The trial will include 3 silos (Early, Late Acute and Chronic PJI) and evaluate treatments and outcome of treatments over a 12 month period. Time points for data collection and analysis will be Day 100 and Day 365 post platform entry.
The Investigators plan to test interventions within 3 initial domains of:
1. Surgical Domain comparing outcomes of surgical strategies - Debridement and Implant Retention (DAIR) vs Revision arthroplasty.
2. Antibiotic Choice Domain comparing outcomes of antibiotic treatment - Backbone antibiotic regimen plus the addition of oral rifampicin (AKA rifampin) vs Backbone antibiotic regimen without rifampicin.
3. Antibiotic Duration Domains comparing the duration of antibiotics treatment in relation to one stage and also two stage surgical Revision arthroplasty strategies
1. Part A - PJI treatment with a single-stage revision - 6 weeks (+/-7 days) of antibiotics following the single stage revision procedure ('short course regimen') vs 12 weeks (+/-7 days) of antibiotics following the single stage revision procedure ('long course regimen')
2. Part B - PJI treatment with a two-stage revision and negative cultures following reimplantation (second stage) - Extended antibiotic prophylaxis: 12 weeks vs No extended prophylaxis.
The ROADMAP trial infrastructure will also have the potential to add further domains to the platform.
RANDOMISATION Participants will be randomly allocated to one arm within each domain for which they are eligible, which their site is participating in, and for which they have consented, using a web-based module available 24h a day 7 days a week. Randomisation within the patient's known silo, for all available domains will occur immediately following provision of consent (which is considered the time of platform entry), however, the reveal of each treatment allocation(s) will be delayed subject to confirmation of domain eligibility.
BLINDING This will be an open-label study unless otherwise specified in a domain-specific appendix. For the overall data and results, only specified members of the statistical analytical team and Data and Safety Monitoring Committee (DSMC) will have access to unblinded results, with other trial investigators and staff remaining blinded to the aggregate results until completion of final analysis for a domain or cell.
ANALYSIS The ROADMAP trial will repeatedly fit Bayesian hierarchical logistic models to the accumulating data (interim analyses), over the life of the trial, to estimate model parameters and evaluate pre-specified decision criteria either within a cell or a whole domain.
CORE PRIMARY OUTCOME MEASURE Treatment success assessed at 12 months post-platform entry, defined as all of: i) Alive; ii) Clinical cure (no clinical or microbiological evidence of infection); iii) No ongoing use of antibiotics for the index joint; and iv) "Destination prosthesis" (the prosthesis present after the initial management strategy is complete) still in place
CORE SECONDARY OUTCOME MEASURES
A core set of secondary endpoints will be evaluated across all domains:
1. A "desirability of outcome ranking" (DOOR - an ordinal outcome which ranks participants based on a combination of clinical cure, patient-reported joint function and quality of life).
2. Patient-reported joint function (Oxford hip or knee score) at 12 months after platform entry.
3. Patient-reported quality of life (EQ5D5L) at 12 months after platform entry
4. Cost effectiveness
5. All-cause mortality at 12 months after platform entry
6. "Clinical cure" at 12 months after platform entry
7. Proportion alive and no longer taking any antibiotics for the index joint at 12 months after platform entry.
8. Proportion in whom the destination prosthesis is still in place at 12 months after platform entry.
9. Microbiological relapse (Positive joint fluid or tissue culture for one or more of the index isolates between Day 100 and 12 months after platform entry)
10. Microbiological reinfection (Positive joint fluid or tissue culture with a different organism to all of the index isolates between Day 100 and 12 months after platform entry).
11. 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
ROADMAP Registry ROADMAP registry is a planned adjunct to the ROADMAP main platform study. The ROADMAP registry aims to describe the entire group of people who get large joint prosthetic joint infections, many of whom have never been a part of other previous research studies. The ROADMAP registry is interested in the different factors that can be examine to identify patterns in the medical history of people that get prosthetic joint infections, what sorts of testing and treatments they receive, and how these might affect their outcome. The registry information when analysed will be used to improve knowledge about prosthetic joint infections and also patient care.
The registry will include participants of the main platform study and also seek independent consent from patients with prosthetic joint infection that choose not to participate in the main platform study. Data for the registry will be collected from participants medical records with participant provided permissions. In addition, all ROADMAP registry participants will be asked to provide specific consent for data linkage that may occur with existing datasets, such as hospital records, national joint replacement registries, and registries of birth, deaths and marriages.
Apart from collecting available information from medical records, there are no additional tests or treatments involved.
PJIs are difficult to treat, because of the presence of a foreign body, which encourages biofilm formation, and the need for combined surgical and prolonged antibiotic management. Outcomes are generally poor, with substantial variation in reported treatment success (ranging from 10 to 90%, median 50% after 2 years) and PJIs have striking health care costs. Existing treatment guidelines are informed by low quality evidence, with fewer than 1,700 participants ever enrolled into published randomised controlled trials comparing management approaches. Defining the optimal surgical and antibiotic approaches to PJI is a critical unmet need.
The Investigators are using an adaptive platform trial to allow the investigators to simultaneously address these questions in the management of PJI. The trial will include 3 silos (Early, Late Acute and Chronic PJI) and evaluate treatments and outcome of treatments over a 12 month period. Time points for data collection and analysis will be Day 100 and Day 365 post platform entry.
The Investigators plan to test interventions within 3 initial domains of:
1. Surgical Domain comparing outcomes of surgical strategies - Debridement and Implant Retention (DAIR) vs Revision arthroplasty.
2. Antibiotic Choice Domain comparing outcomes of antibiotic treatment - Backbone antibiotic regimen plus the addition of oral rifampicin (AKA rifampin) vs Backbone antibiotic regimen without rifampicin.
3. Antibiotic Duration Domains comparing the duration of antibiotics treatment in relation to one stage and also two stage surgical Revision arthroplasty strategies
1. Part A - PJI treatment with a single-stage revision - 6 weeks (+/-7 days) of antibiotics following the single stage revision procedure ('short course regimen') vs 12 weeks (+/-7 days) of antibiotics following the single stage revision procedure ('long course regimen')
2. Part B - PJI treatment with a two-stage revision and negative cultures following reimplantation (second stage) - Extended antibiotic prophylaxis: 12 weeks vs No extended prophylaxis.
The ROADMAP trial infrastructure will also have the potential to add further domains to the platform.
RANDOMISATION Participants will be randomly allocated to one arm within each domain for which they are eligible, which their site is participating in, and for which they have consented, using a web-based module available 24h a day 7 days a week. Randomisation within the patient's known silo, for all available domains will occur immediately following provision of consent (which is considered the time of platform entry), however, the reveal of each treatment allocation(s) will be delayed subject to confirmation of domain eligibility.
BLINDING This will be an open-label study unless otherwise specified in a domain-specific appendix. For the overall data and results, only specified members of the statistical analytical team and Data and Safety Monitoring Committee (DSMC) will have access to unblinded results, with other trial investigators and staff remaining blinded to the aggregate results until completion of final analysis for a domain or cell.
ANALYSIS The ROADMAP trial will repeatedly fit Bayesian hierarchical logistic models to the accumulating data (interim analyses), over the life of the trial, to estimate model parameters and evaluate pre-specified decision criteria either within a cell or a whole domain.
CORE PRIMARY OUTCOME MEASURE Treatment success assessed at 12 months post-platform entry, defined as all of: i) Alive; ii) Clinical cure (no clinical or microbiological evidence of infection); iii) No ongoing use of antibiotics for the index joint; and iv) "Destination prosthesis" (the prosthesis present after the initial management strategy is complete) still in place
CORE SECONDARY OUTCOME MEASURES
A core set of secondary endpoints will be evaluated across all domains:
1. A "desirability of outcome ranking" (DOOR - an ordinal outcome which ranks participants based on a combination of clinical cure, patient-reported joint function and quality of life).
2. Patient-reported joint function (Oxford hip or knee score) at 12 months after platform entry.
3. Patient-reported quality of life (EQ5D5L) at 12 months after platform entry
4. Cost effectiveness
5. All-cause mortality at 12 months after platform entry
6. "Clinical cure" at 12 months after platform entry
7. Proportion alive and no longer taking any antibiotics for the index joint at 12 months after platform entry.
8. Proportion in whom the destination prosthesis is still in place at 12 months after platform entry.
9. Microbiological relapse (Positive joint fluid or tissue culture for one or more of the index isolates between Day 100 and 12 months after platform entry)
10. Microbiological reinfection (Positive joint fluid or tissue culture with a different organism to all of the index isolates between Day 100 and 12 months after platform entry).
11. 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
ROADMAP Registry ROADMAP registry is a planned adjunct to the ROADMAP main platform study. The ROADMAP registry aims to describe the entire group of people who get large joint prosthetic joint infections, many of whom have never been a part of other previous research studies. The ROADMAP registry is interested in the different factors that can be examine to identify patterns in the medical history of people that get prosthetic joint infections, what sorts of testing and treatments they receive, and how these might affect their outcome. The registry information when analysed will be used to improve knowledge about prosthetic joint infections and also patient care.
The registry will include participants of the main platform study and also seek independent consent from patients with prosthetic joint infection that choose not to participate in the main platform study. Data for the registry will be collected from participants medical records with participant provided permissions. In addition, all ROADMAP registry participants will be asked to provide specific consent for data linkage that may occur with existing datasets, such as hospital records, national joint replacement registries, and registries of birth, deaths and marriages.
Apart from collecting available information from medical records, there are no additional tests or treatments involved.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: