Condition category
Infections and Infestations
Date applied
25/05/2018
Date assigned
30/05/2018
Last edited
30/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Prosthetic (artificial) replacement of poorly functioning, painful and diseased joints is now a common surgical procedure. However, late prosthetic joint infections (LPJI), caused by blood-borne bacteria (bacteremia), are a common complication with high morbidity, and potential mortality, as well as high treatment, patient and societal costs. In an attempt to reduce the risk of LPJI, dentists in some parts of the world (particularly the US) are recommended to routinely give prosthetic joint patients antibiotics before invasive dental procedures (IDP). This is called antibiotic prophylaxis (AP). The purpose of this is to reduce the risk of procedure-related bacteremia causing infection of the prosthetic joint. However, there is little evidence to demonstrate any association between IDP and LPJI and there is no clinical trial data demonstrating the efficacy, or not, of AP. Currently AP is not recommended in the UK for individuals with prosthetic joints but is in the US. Data proving or disproving any association between IDP and LPJI is urgently needed. If an association exists, then the widespread adoption of AP in the UK and elsewhere could help reduce the large number of LPJI cases and high associated treatment costs. In the US alone there are ~20,000 LPJI cases with a ~$566 million annual treatment cost. Alternatively, if no association exists, then AP is unnecessary and a clear recommendation against its use could be made. As AP is not currently recommended in the UK this would not have a significant impact other than reassuring clinicians and patients. In the US, and other countries where AP is the standard of care, however, stopping AP would save ~$60 million annually, avoid the risk of adverse reactions in those who currently receive AP and reduce the risk posed to society that AP unnecessarily promotes the development of antibiotic resistant bacteria.

Who can participate?
All individuals admitted to hospital for late prosthetic joint infections (LPJI) in England.

What does the study involve?
This study uses national hospital admissions data to identify all those individuals in England who developed a LPJI in the period between 1st April 2010 and the 31st March 2017 and link this to national dental treatment data to see if those who developed LPJI were more likely, or not, to have had an invasive dental procedure performed in the 3 months immediately preceding their LPJI than in any other 3 month period.

What are the possible benefits and risks of participating?
If this study demonstrates a link between invasive dental procedures and LPJI, this will provide support for the use of antibiotic prophylaxis (AP) before invasive dental procedures in patients with prosthetic joints. If no such link is identified, it will provide reassurance to those with prosthetic joints, their dentists and physicians, carers and those charged with providing guidance on such issues, that current UK guidance not to provide AP for those with prosthetic joints is correct.
In countries such as the US, where AP is recommended for those with prosthetic joints undergoing invasive dental procedures, the demonstration of a link between invasive dental procedures and LPJI would lend support for this guidance. On the other hand, if no link was demonstrated, it would provide support for the idea that AP might not be necessary.
While this research will not directly benefit individuals in the data set, it will help to improve evidence based dental care for all those with prosthetic joints. As it is an observational study, there is no direct risk for participants.

Where is the study run from?
University of Sheffield (UK)

When is the study starting and how long is it expected to run for?
May 2017 to March 2021

Who is funding the study?
National Institutes of Health (UK)

Who is the main contact?
Prof Martin Thornhill (Scientific)

Trial website

Contact information

Type

Scientific

Primary contact

Prof Martin Thornhill

ORCID ID

http://orcid.org/0000-0003-0681-4083

Contact details

University of Sheffield School of Clinical Dentistry
Claremont Crescent
Sheffield
S10 2TA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

University of Sheffield 154006; NIH 1 R01 DE027917-01

Study information

Scientific title

A retrospective, case-crossover design, observational study of English national data comparing the incidence of invasive dental procedures in the 3 months immediately preceding a late prosthetic joint infection (cases) with the incidence of invasive dental procedures in earlier 3-month control periods (3-6, 6-9 or 9-12 months before a late prosthetic joint infection)

Acronym

Study hypothesis

Null hypothesis: There is no temporal association between invasive dental procedures and the development of late prosthetic joint infections (LPJI)

Ethics approval

National Health Service (NHS) Health Research Authority (HRA) Research Ethics Service (RES) of the United Kingdom - submission pending

Study design

Case crossover design observational study

Primary study design

Observational

Secondary study design

Case crossover study

Trial setting

Other

Trial type

Prevention

Patient information sheet

No participant information sheet available

Condition

Invasive dental procedures leading to development of late prosthetic joint infections

Intervention

We do not intend to contact patients or involve them personally with this research, the proposed research is an observational study only. It uses routinely collected national data for England.

The study will link national data on courses of dental treatment (NHS Business Service Authority Dental Database) and hospital admissions for prosthetic joint infection (Hospital Episode Statistics (HES) database) to investigate if there is a link between invasive dental procedures and the development of late prosthetic joint infections (LPJI) i.e. prosthetic joint infections occurring >3 months after joint placement.

NHS Digital is the HES data guardian. NHS Digital identifies all patients admitted to hospital between 1st April 2010 and 31st March 2017 (7 years) with a primary or secondary diagnosis of a joint infection using ICD-10 codes M00.0, M00.1, M00.2, M00.8, M00.9 - approximately 87,000 individuals. This data includes hospital admissions data for these individuals back to January 2000 and is later be used to confirm that the patient had a prosthetic joint inserted and that the joint was replaced more than 3 months prior to development of the joint infection i.e. those who fulfilled the criteria for LPJI. Such individuals are identified by searching the records of those identified as having a joint infection between 1st April 2010 and 31st March 2017 back to January 2000 for any admission for insertion of a prosthetic joint using OPCS-4 operative procedure codes W37-W51 more than 3 months before the joint infection admission. From the list of individuals admitted with a joint infection between 1st April 2010 and 31st March 2017, NHS Digital creates two datasets, linked by a unique study ID for each patient.

These datasets are:
Dataset 1: Contains patient identifiers and the unique study ID (but no HES clinical data). This is sent to managers of the NHS Business Services Authority (NHSBSA) Dental Database. NHSBSA identify the dental records for these patients. Included in this is the date of any course of dental treatment and whether the treatment included any extraction, endodontic treatment or a scale and polish i.e. any invasive dental procedure (IDP). NHSBSA remove the patient identifiers from this dataset but retain the unique study ID against each record i.e. they de-identify the data. The de-identified dental records of study patients (with just the unique study ID) are sent to the University of Sheffield study team. NHSBSA then securely destroy their copy of dataset 1 and notify NHS Digital of it's destruction.

Dataset 2: Contains the hospital admissions data for each patient back to January 2000 (this is necessary to confirm that the infection occurred in someone with a prosthetic joint and to enable the study team to identify those patients who had a prosthetic joint inserted >3 months before the joint infection) and the unique study ID (but no patient identifying information) i.e. it is de-identified data. This data is sent by NHS Digital to the University of Sheffield study team.

The University of Sheffield study team receive the de-identified Datasets 1 and 2. The data within the two de-identified data sets is then linked using the common unique study ID for each patient and this data is used for the study analysis. The University of Sheffield study team thus receive linked hospital admission and dental data but receive no patient identifying details and have no means of identifying patients from the unique study ID number.

Identifiable patient data is only transferred between the two NHS organsations (NHS Digital and NHSBSA). The study team at the University of Sheffield do not receive any patient identifiable data.
The research team at the University of Sheffield analyse the data according to the study protocol and report the results through peer reviewed journals, a report to NIH (who are funding the study) and conference proceedings.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Incidence of invasive dental procedures in the 3 months immediately preceding a late prosthetic joint infection (LPJI) (case period) compared to the frequency of invasive dental procedures in earlier 3 month control periods (3-6, 6-9 and 9-12 month before LPJI), measured by linking national hospital diagnosis and procedure data with national dental treatment data

Secondary outcome measures

LPJI free survival following a course of dental treatment involving an invasive dental procedure (cases) compared to LPJI free survival following a course of dental treatment NOT involving an invasive dental procedure (controls) measured by linking national hospital diagnosis and procedure data with national dental treatment data.
Invasive dental procedures are defined as extractions, dental scaling and endodontic (root canal) treatment.

Overall trial start date

07/05/2017

Overall trial end date

31/03/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Developed a prosthetic joint infection as a primary or secondary discharge diagnosis (ICD-10 codes M00.0, M00.1, M00.2, M00.8, M00.9)
2. >3 months after having had a prosthetic joint inserted (OPCS-4 codes W37-W51)

Participant type

Patient

Age group

All

Gender

Both

Target number of participants

There is no target number. We anticipate around 100,000 individuals will be identified with a joint infection during the period between 1st April 2010 and the 31st March 2017.

Participant exclusion criteria

1. NHS number is missing or cannot be derived using established algorithms from their other personally identifying data (name, date of birth, gender, address etc.). Any missing or corrupt records are also excluded
2. Prosthetic joint was inserted <3 months before the prosthetic joint infection are also excluded
3. Notified NHS Digital or NHSBSA that they do not wish their data to be shared for purposes other than their own direct care (known as a 'Type 2 Opt-Out')

Recruitment start date

01/04/2010

Recruitment end date

31/03/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Sheffield
S10 2TA
United Kingdom

Sponsor information

Organisation

University of Sheffield

Sponsor details

School of Clinical Dentistry
Claremont Crescent
Sheffield
S10 2TA
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institutes of Health

Alternative name(s)

NIH

Funding Body Type

government organisation

Funding Body Subtype

federal/national government

Location

United States of America

Results and Publications

Publication and dissemination plan

Planned publication of the findings of this study in a high-impact peer reviewed international dental, orthopaedic or general medical journal and expected presentation of the data at national or international dental and/or orthopaedic research meetings soon after completion of the study.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available as this study links data from two English national data sets (i) the National Health Service (NHS) NHS Digital Hospital Episode Statistics database of hospital admission diagnoses and procedures and (ii) the NHS Business Services Authority (NHSBSA) dental database. Although these two NHS organisations use patient identifying information to link the data at the patient level, the data is then de-identified before being made available to the research team. The research team do not, therefore, have access to identifiable patient level data. Furthermore, it is a requirement of these two national data organisations that patient level data is not made available by researchers but remains entirely under the control and care of these organisations i.e. NHS Digital and NHSBSA.

Intention to publish date

31/03/2022

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes