Condition category
Surgery
Date applied
16/07/2018
Date assigned
17/07/2018
Last edited
22/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 November 2021

Who is funding the study?
Heraeus Medical GmbH

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

Trial website

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

Contact information

Type

Scientific

Primary contact

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

Additional contact

Prof Mike Reed

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

38386

Study information

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

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

Trial setting

Hospitals

Trial 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

Phase

Drug names

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 trial start date

15/12/2017

Overall trial end date

15/11/2021

Reason abandoned (if study stopped)

Eligibility

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

Patient

Age group

Senior

Gender

Both

Target number of participants

Planned Sample Size: 4920; UK Sample Size: 4920

Participant exclusion criteria

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

Recruitment start date

01/08/2018

Recruitment end date

30/04/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Norfolk & Norwich University Hospital
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Poole Hospital
Poole
BH15 2JB
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Royal Berkshire Hospital
Reading
RG1 5AN
United Kingdom

Trial participating centre

Princess Royal Hospital
Haywards Heath
RH16 4EX
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Southmead Hospital
Bristol
BS10 5NB
United Kingdom

Trial participating centre

University Hospital Coventry
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

University Hospital Wales
Cardiff
CF64 2XX
United Kingdom

Sponsor information

Organisation

Northumbria Healthcare NHS Foundation Trust

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

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

Funders

Funder type

Industry

Funder name

Heraeus Medical GmbH

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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.

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available.

Intention to publish date

01/05/2022

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/03/2019: The condition was updated. 18/07/2018: Internal review.