A randomised controlled trial of single antibiotic cement versus dual antibiotic cement in patients receiving a partial hip joint replacement after fracture

Plain English Summary

Background and study aims
This study is comparing two types of treatments in patients who have suffered a hip fracture and need to have a partial hip replacement (also called a hemiarthroplasty). The hemiarthroplasty implant is inserted into the thigh bone and replaces the ‘ball’ part of the ‘ball-and-socket’ hip joint. ‘Bone cement’ is used to hold the implant in place. This study aims to compare two different antibiotic bone cement mixtures used to hold the implant in place. The results of this trial should show whether there is any difference in the rate of deep infection in patients when one of the two bone cement mixtures is used to hold their hemiarthroplasty implant in place. The information gained will help patients and their doctors make more informed decisions about the best way to reduce the risk of deep infection in this type of surgery.

Who can participate?
Patients 60 years of age or older who have been admitted to a participating hospital with a hip fracture that the surgeon feels should be treated with a hip hemiarthroplasty

What does the study involve?
Participants are randomly allocated to receive one of two types of bone cement. The first type has a lower dose of a single type of antibiotic, and the second type has a higher dose of that same antibiotic, as well as a second type of antibiotic. Participants complete a questionnaire about their recovery by telephone at 120 days after their surgery.

What are the possible benefits and risks of participating?
There is no specific advantage to patients from taking part in the study. However, the results of this study will help to decide which treatment is best for patients with this type of injury. Any operation for a broken hip carries some risks. The risks of surgery with an implant include: bleeding requiring blood transfusion, infection, further fracture, dislocation, leg length discrepancy, blood clots, damage to nerves and blood vessels in the surgical area, and the risks associated with the anaesthetic. These risks are the same as for patients who are not part of this study. There are also uncommon risks associated with both types of cement. In a small number of cases, patients having a cemented replacement can have a reaction to the bone cement. If this were to occur, the anaesthetist and surgeon would continue treatment as per normal practice. This risk is the same for both types of bone cement.

Where is the study run from?
The study is sponsored by the Northumbria Healthcare NHS Foundation Trust and is managed by Oxford Trauma, a clinical trials research group which is a part of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) at the University of Oxford. There will be 20+ hospitals from across the United Kingdom participating in the study.

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

Who is funding the study?
Heraeus Medical GmbH

Who is the main contact?
Stephanie Wallis
white8-copal@ndorms.ox.ac.uk

Study website

https://white8.octru.ox.ac.uk/

Type

Scientific

Contact name

Ms Stephanie Wallis

ORCID ID

Contact details

Northumbria Healthcare NHS Foundation Trust
Woodhorn Lane
Ashington
NE63 9JJ
United Kingdom
+44 (0)1865 223111
White8-copal@ndorms.ox.ac.uk

Type

Scientific

Contact name

Prof Mike Reed

ORCID ID

Contact details

Northumbria Healthcare NHS Foundation Trust
Woodhorn Lane
Ashington
NE63 9JJ
United Kingdom

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

38386

Scientific title

WHiTE 8 COPAL: a randomised controlled trial of low dose single antibiotic loaded cement versus high dose dual antibiotic loaded cement in patients receiving a hip hemiarthroplasty after fracture

Acronym

WHiTE 8 COPAL

Study hypothesis

This trial aims to establish if a high dose, dual antibiotic regime has fewer infections compared to low dose single antibiotic cement.

Ethics approval(s)

Wales REC 5, 03/05/2018, ref: 18/WA/0154

Study design

Randomised; Interventional; Design type: Treatment, Surgery

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Hip fracture

Intervention

Participants will undergo surgery at the next available opportunity on a planned trauma list. Participants will be blinded to the treatment allocation. The operating surgeon will not be blinded to the allocation. Where possible clinical outcomes will be assessed by blinded assessors. Patients will be kept blinded until the completion of the trial when the blind may be broken.

Group 1: Cemented hemiarthroplasty with low dose single antibiotic cement
Replacement of the femoral head and neck with choice of femoral head and stem. Cement used will be Heraeus Palacos R+G cement (Hanau, Germany) – contains gentamicin 0.5 grams per 40 gram mix of cement.

Group 2: Cemented hemiarthroplasty with high dose dual antibiotic cement
Replacement of the femoral head and neck with choice of femoral head and stem. Cement used will be Heraeus Copal G+C cement (Hanau, Germany) – contains gentamicin 1 g and clindamycin 1 g per 40 gram mix of cement.

Following fixation all patients will undergo a routine rehabilitation prior to discharge from hospital. Research staff will complete the infection-related questions at baseline, and at 4 months (120 days) post-surgery. In addition the following data will be collected:
1. Demographic and baseline characteristics (e.g. age, gender, pre-fracture mobility)
2. Routine 'operation notes' and 'discharge summaries' that include details of patient's diagnosis and treatment, perioperative complications, and discharge details
3. Medical record review for diagnosis of infection
4. Details of admission, assessment and treatment
5. Details of antibiotics use and microbiological reports for reported infections
6. Contact details, including of carers when appropriate
7. Complications and SAEs during the study period

Following their 4-month questionnaire, patients will have completed their participation in the trial and will continue to be treated as per normal standard of care.

Intervention type

Procedure/Surgery

Primary outcome measure

Deep Infection of surgical wound; the trialists will use the Centre for Disease Control and Prevention definition of a “deep surgical site infection”, that is a wound infection involving the tissues deep to the skin that occurs within 90 days of injury. Medical records for all patients will be reviewed by appropriately trained staff for indicators of infection at the time of the patient’s discharge from the research site. In addition, at 120 days post-surgery, the patients will self-report (via telephone interview, electronic media or postal questionnaire) on signs of infections. When potential signs of infection have been found, either at discharge or 120 days, the site will be asked to provide, if available, copies of: any re-operation records for surgery related to the index hip fracture, details of antibiotics prescribed, microbiology reports if samples of the suspected infected tissues around the hip were sent for analysis and imaging reports for any deep imaging that occurred in relation to suspected infection. These data will be collated by the central trial team in Oxford.

Secondary outcome measures

1. Mortality recorded at discharge from the research site as well as in the 120-day follow-up. Sites or consultees may also report mortality at any point in the time between discharge and 120 days.
2. Health-related quality of life measured by EuroQol EQ-5D-5L at baseline and at 120 days post-surgery
3. All complications and surgical interventions related to the index wound will be recorded. These are reported by sites as they become aware of events, as well as by patients, carers or consultees at 4 months (120 days)
4. Antibiotic prescription information will be obtained from the patient, consultee or carer at the 4 months (120 days) follow-up. Should the patient be entered into the trial under nominated consultee agreement and this information not be available from a carer, the trial team may contact the patient’s GP for this information
5. Resistance patterns of infections; all infections identified in the primary endpoint will be assessed for antibiotic resistance profiles by the local microbiology team
6. Resource use; cost data will be obtained from national databases or will be estimated in consultation with the hospital finance department. The cost consequences following discharge, including NHS costs and patients' out-of-pocket expenses will be recorded via a short questionnaire, which will be administered at 4 months (120 days) post-surgery. This will be either by patient or consultee
7. Mobility; the ability to walk indoors and outdoors is rated very highly by patients. It has been included in a recommended ‘core outcome set’ for trials assessing interventions in hip fractures, hence it will be recorded using the CRF. It will be captured at baseline and at 4 months (120 days).
8. Residential status; also captured on CRF. The residential status is also part of the core outcome set for hip fractures and NHFD dataset. It will be captured at baseline and at 4 months (120 days)

Overall study start date

15/12/2017

Overall study end date

31/12/2021

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Aged 60 years or older
2. Intracapsular hip fracture, which in the opinion of the treating surgeon requires acute surgical treatment with a cemented hip hemiarthroplasty

Participant type(s)

Patient

Age group

Senior

Sex

Both

Target number of participants

Planned Sample Size: 4920; UK Sample Size: 4920

Total final enrolment

4936

Participant exclusion criteria

Patients will be excluded if they are allergic to gentamicin or clindamycin

Recruitment start date

01/08/2018

Recruitment end date

31/08/2021

Countries of recruitment

England, United Kingdom, United States of America, Wales

Study participating centre

John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom

Study participating centre

Leicester Royal Infirmary
Musculoskeletal Research Office
Ground Floor, Victoria Building
Leicester
LE1 5WW
United Kingdom

Study participating centre

Norfolk & Norwich University Hospital
Orthopaedic Research
East Block Level 2
Colney Lane
Norwich
NR4 7UY
United Kingdom

Study participating centre

Poole Hospital
Research Dept
Cornelia House
Longfleet Road
Poole
BH15 2JB
United Kingdom

Study participating centre

Queen Alexandra Hospital
ED Research Team
Lancaster House
Portsmouth
PO6 3LY
United Kingdom

Study participating centre

Queen Elizabeth Hospital
NIHR SRMRC
4th Floor
North Block
Institute of Translational Medicine
Hertiage Building
Birmingham
B15 2TH
United Kingdom

Study participating centre

Royal Berkshire Hospital
Research and Development
Level 2 | North Block
London Road
Reading
RG1 5AN
United Kingdom

Study participating centre

Princess Royal Hospital
Research & Development
Sussex House
1 Abbey Road
Brighton
BN12 1ES
United Kingdom

Study participating centre

Royal Victoria Infirmary
Peacock Hall
Level 2, Room 12
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Study participating centre

Southmead Hospital
Trauma & Orthopaedic Research Team
Department of Orthopaedics
Office 6, Gate 18, Level 1
Brunel Building
Bristol
BS10 5NB
United Kingdom

Study participating centre

University Hospital Coventry
Trauma & Orthopaedic Research Team
Research & Development
Room ACF40002
4th Floor, West Wing
UHCW, Clifford Bridge Road
Walsgrave
Coventry
CV2 2DX
United Kingdom

Study participating centre

Queens Medical Centre
T & O Research Manager
Trauma & Orthopaedic Audit Office
C Floor, West Block, QMC (WC1285)
Nottingham University Hospitals
Nottingham
NG7 2UH
United Kingdom

Study participating centre

University Hospital Wales
Trauma & Orthopaedics Directorate
Cardiff & Vale University Health Board
Cardiff & Vale Orthopaedic Centre (CAVOC)
University Hospital Llandough
Penlan Road
Penarth
Cardiff
CF64 2XX
United Kingdom

Study participating centre

University Hospital Aintree
John Moorehead
Orthopaedic Research Room
Fracture Clinic
Lower Lane
Liverpool
L9 7AL
United Kingdom

Study participating centre

Salford Royal Hospital
Stott Lane
Salford
M6 8HD
United Kingdom

Study participating centre

Morriston Hospital
Heol Maes Eglwys
Morriston
SA6 6NL
United Kingdom

Study participating centre

Wythenshawe Hospital
University Hospital of South Manchester
Southmoor Road
Wythenshawe
M23 9LT
United States of America

Study participating centre

Blackpool Victoria Hospital
Clinical Research Centre
2nd Flor, Area 5
Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom

Study participating centre

Ipswich Hospital
The East Suffolk North Essex NHS Foundation Trust
Heath Road
Ipswich
IP4 5PD
United Kingdom

Study participating centre

James Cook University Hospital
Academic Centre
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Study participating centre

Sandwell General Hospital
Sandwell & West Birmingham Hospitals NHS Trust
Sandwell Medical Research Unit
Opposite Diabetes Centre
Lyndon
West Bromwich
B71 4HJ
United Kingdom

Study participating centre

Royal Cornwall Hospital
Medical & Surgical Research Team
B16 Knowledge Spa
Royal Cornwall Hospitals NHS Trust
Truro
TR1 3HD
United Kingdom

Study participating centre

Northumbria Specialist Emergency Care Hospital
Wansbeck General Hospital
Woodhorn Lane
Ashington
NE63 9JJ
United Kingdom

Study participating centre

Kings College Hospital
Orthopaedic Department
2nd Floor, Hambleden Wing
Denmark Hill
London
SE5 9RS
United Kingdom

Study participating centre

Horton General Hospital
Oxford Road
Banbury
OX16 9AL
United Kingdom

Organisation

Northumbria Healthcare NHS Foundation Trust

Sponsor details

North Tyneside General Hospital
Rake Lane
North Shields
Tyne & Wear
North Shields
NE29 8NH
England
United Kingdom
+44 (0)344 811 8111
white8-copal@ndorms.ox.ac.uk

Sponsor type

Hospital/treatment centre

Website

https://www.northumbria.nhs.uk/

ROR

https://ror.org/01gfeyd95

Funder type

Industry

Funder name

Heraeus Medical GmbH

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Protocol will be published after the start of the trial. Planned publication of the results in a high-impact peer reviewed journal.

Intention to publish date

01/05/2023

Individual participant data (IPD) sharing plan

All data generated or analysed during this study will be included in the subsequent results publication

IPD sharing plan summary

Published as a supplement to the results publication

Study outputs