Randomised Arthroplasty Infection Worldwide Multidomain Adaptive Platform (ROADMAP) Trial

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.

Conditions

• Prosthetic Joint Infections of Hip
• Prosthetic Joint Infections of Knee
• Large Joint Prosthetic Joint Infections

Interventions

PROCEDURE

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.

DRUG

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.

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• Hunter Medical Research Institute (HMRI)

  collaborator UNKNOWN

• The University of Western Australia

  collaborator OTHER

• Michael Garron Hospital

  collaborator OTHER

• Aotearoa Clinical Trials

  collaborator UNKNOWN

• Exeter Orthopaedic Trial unit

  collaborator UNKNOWN

• University of Sydney

  collaborator OTHER

• University of Melbourne

  collaborator OTHER

• The Peter Doherty Institute for Infection and Immunity

  collaborator OTHER

• University of Newcastle, Australia

  lead OTHER

Principal Investigators

• Joshua S Davis. Co-chief Investigator, infectious diseases Specialist · University of Newcastle, Menzies Institute, Hunter Medical Research Institute, Hunter New England Health

• Laurens Manning, Co-chief Investigator, infectious diseases Specialist · The University of Western Australia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-26

Primary Completion

2028-02-18

Completion

2029-12-31

Countries

• Australia

Study Locations