The RandOmised Arthroplasty Infection worlDwide Multidomain Adaptive Platform (ROADMAP) Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 2,500
- 试验地点
- 60
- 主要终点
- Treatment success at 12 months
研究概览
简要总结
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:
- 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.
详细描述
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:
- Surgical Domain comparing outcomes of surgical strategies - Debridement and Implant Retention (DAIR) vs Revision arthroplasty.
- 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.
- Antibiotic Duration Domains comparing the duration of antibiotics treatment in relation to one stage and also two stage surgical Revision arthroplasty strategies
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •"Confirmed" or "Likely" Prosthetic joint infection of a large joint according to European Bone and Joint Infection Society (EBJIS) criteria (2021)
- •Physically present at participating hospital at time of eligibility assessment
- •"Current" prosthetic joint infection, meaning symptoms and/or signs of the PJI are present at the time of eligibility assessment.
排除标准
- •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):
- •The index prosthetic joint is a shoulder, elbow, wrist or ankle.
- •Known previous participation in the randomised ROADMAP randomised platform for the index joint.
- •Known previous participation in the randomised ROADMAP platform for a joint other than the index joint within the 12 months prior to eligibility assessment
- •Treating clinician believes that death is imminent and inevitable.
- •Treatment is not with curative intent.
- •Patient is not classifiable into one of the three defined silos.
- •Patient is unlikely to be accessible for follow up over the 12 months following platform entry.
- •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:
- •Onset of symptoms is >30 days after implantation of the index joint
- •Treating team feel that either DAIR or revision is appropriate for this patient.
- •The infected prosthesis is a primary arthroplasty. Surgical Strategy Domain: Late Acute Silo exclusion criteria
- •Any previous episode of native joint septic arthritis or PJI in the index joint
- •A definitive DAIR has already occurred for this episode of infection.
- •A revision has already occurred for this episode of infection
- •Loosening or instability of any component of the prosthesis
- •Predicted inadequate soft tissue coverage for wound closure
- •One or more of the causative organisms is a fungus or a "difficult to treat" bacterium.
- •Treating team deems enrolment in this domain is not in the best interests of the patient.
- •Antibiotic Choice Domain inclusion criteria
- •The time of eligibility assessment is between 48h and 7 days following initial surgical treatment.
- •One or more of the causative organisms is a Gram-positive of interest OR the infection is culture negative.
- •Antibiotic Choice Domain exclusion criteria
- •Previous hypersensitivity reaction to rifampicin
- •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.
- •One or more causative Gram-positive organisms of interest have in-vitro evidence of resistance to rifampicin
- •Known pregnancy or breastfeeding
- •Treating team deems enrolment in this domain is not in the best interests of the patient.
- •Antibiotic Duration Part A Domain inclusion criteria
- •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:
- •Any causative organism is a fungus or a 'difficult-to-treat' bacterium at the time of platform entry
- •Treating team deems enrolment in this domain is not in the best interests of the patient
- •The single stage revision was >7 days ago
- •Patient no longer willing to participate in the domain
- 另有 25 项未显示
研究组 & 干预措施
4. ANTIBIOTIC DURATION DOMAIN Part B - Two Stage Revision
No extended antibiotic prophylaxis versus extended antibiotic prophylaxis following a two-stage revision.
干预措施: Antibiotic Duration Part B - Two stage revision (Drug)
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)
干预措施: Debridement and Implant Retention (DAIR) (Procedure)
2. ANTIBIOTIC CHOICE DOMAIN
Backbone therapy alone (active comparator) versus Backbone antibiotic therapy plus Rifampicin.
干预措施: Antibiotic Choice (Drug)
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).
干预措施: Antibiotic duration Part A - Single stage revision (Drug)
结局指标
主要结局
Treatment success at 12 months
时间窗: 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.
次要结局
- A "desirability of outcome ranking" DOOR(Platform entry until day 265)
- Patient-reported joint function (Oxford hip or knee score) at 12 months after platform entry.(platform entry until day 365)
- Patient-reported quality of life (EuroQol-5 Dimensions-5 Levels (EQ5D5L)) at 12 months after platform entry.(Platform entry until day 365)
- Cost effectiveness over the first 12 months after platform entry.(From platform entry until day 365)
- All-cause mortality at 12 months after platform entry(From platform entry until day 365)
- "Clinical cure" at 12 months after platform entry (as defined in the primary outcome)(From platform entry until day 365)
- Proportion alive and no longer taking any antibiotics for the index joint at 12 months after platform entry (as defined in the primary outcome).(From platform entry until day 365)
- Proportion in whom the destination prosthesis is still in place at 12 months after platform entry (as defined in the primary outcome)(From platform entry until day 365)
- Microbiological relapse(From platform entry until day 100 and day 365)
- Microbiological reinfection(From platform entry until day 100 and day 365)
- 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(From platform entry until 24 months)