Condition category
Surgery
Date applied
01/03/2019
Date assigned
08/05/2019
Last edited
13/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
55,000 women are diagnosed with breast cancer each year in the UK. 40% undergo mastectomy (surgical removal of the breast) and of those who choose breast reconstruction, most will have an implant-based operation.
Traditionally, implant-based reconstructions have been performed by placing the implant under the chest wall (pectoral muscle) with or without a biological or synthetic mesh to support it. This gives a good result but lifting the muscle can be painful and some women dislike the upward movement of the implant that is seen when the chest wall muscle contracts often called implant ‘animation’.
Recently new techniques have been introduced in which the implant wrapped in mesh is placed on top of, rather than under the muscle. These techniques called prepectoral implant reconstruction may be less painful and may give more natural-looking results as well as avoiding problems with implant animation.
Although these techniques are gaining in popularity, there is no good evidence to suggest that they are as safe or effective as standard submuscular reconstruction. Ideally, the two techniques should be fairly compared in a randomised trial but the prepectoral technique is still changing and only a limited number of surgeons are able to offer this to patients. Before a trial can be considered it is necessary to:
1. Determine whether prepectoral techniques are safe by measuring complications including the need to remove the implant at 3 months
2. Explore whether the technique has stopped changing and is now stable and ready for evaluation
3. Create a network of surgeons who are able to perform prepectoral reconstructions and could take part in a future trial

Who can participate?
Women aged over 16 undergoing mastectomy for breast cancer or risk reduction and electing to undergo immediate prepectoral implant-based breast reconstruction

What does the study involve?
Patients will be asked to sign a consent form and complete questionnaires before the operation. They will have an operation and see a surgeon and their team as normal following surgery. Patients will be asked to complete postoperative pain scores at 24 hours, 48 hours, 1 week following surgery and quality of life and satisfaction questionnaires at 3 and 18 months after their operation. These can be completed online or paper according to patient preference The questionnaires should take no more than 30 minutes to complete.

What are the possible benefits and risks of participating?
There are no benefits to individual participants, but the information collected during the study might help women make choices regarding breast reconstruction in future. There are no risks involved in trial participation beyond the inherent risks of surgery, which will be explained by individual surgeons and are independent of the study.

Where is the study run from?
University of Bristol and 37 recruiting sites (UK)

When is the study starting and how long is it expected to run for?
October 2017 to February 2022 - recruiting from June 2019 to June 2020

Who is funding the study?
1. The Bristol NIHR Biomedical Research Centre (UK)
2. The Royal College of Surgeons of England (UK)
3. The Association of Breast Surgeons (UK)

Who is the main contact?
Miss Shelley Potter
prebra-study@bristol.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Shelley Potter

ORCID ID

http://orcid.org/0000-0002-6977-312X

Contact details

Centre for Surgical Research
Bristol Medical School
Canynge Hall
Whatley Road
Bristol
BS8 2PS
United Kingdom
+44 (0)7815684182
prebra-study@bristol.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

2.0

Study information

Scientific title

The Pre-pectoral Breast Reconstruction Evaluation Feasibility Study - a mixed-methods IDEAL 2a/2b prospective cohort study to determine the safety and effectiveness of pre-pectoral implant-based breast reconstruction

Acronym

Pre-Bra

Study hypothesis

Current study hypothesis as of 08/04/2020:
Pre-pectoral breast reconstruction is safe and the technique is stable and ready for evaluation in a definite randomised controlled trial.

Previous study hypothesis:
Pre-pectoral breast reconstruction is safe and results in levels of pain and implant animation following surgery which are acceptable to patients.

Ethics approval

Approved 10/05/2019, NHS HRA South Central - Oxford B Research Ethics Committee (Whitefriars, Level 3, Block B, Lewin's Mead, Bristol, BS1 2NT; 0207 104 8168; nrescommittee.southcentral-oxfordb@nhs.net), ref: 19/SC/0129, HRA/HCRW approval 14/05/2020

Study design

Mixed methods IDEAL 2a/2b prospective observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request participant information sheet

Condition

Breast reconstruction

Intervention

It is anticipated that patients entering the study will be followed up for 18 months.

Screening (using SEAR method)
Screening data will not include any patient identifiable information:
1. All patients electing to undergo IBBR
2. Number technically suitable for PPBR
3. Number not considered technically suitable for PPBR and reasons for this
4. Number accepting PPBR
5. Number accepting study participation

Baseline pre-operative assessment
1. Patient demographic data captured
2. BREAST-Q completed (Reconstruction-pre-operative version)

Surgical admission
1. PPBR procedure: operative data captured
2. Length of post-operative hospital stay
3. Post-operative pain at 24 hours or point of discharge
4. Any immediate in-hospital complications

Early clinical follow-up
1. Post-operative pain score at 1 and 2 weeks electronically self-reported by the patient if no longer in hospital
2. Assessment and recording of complications at clinical review: timing as per each site’s routine standard of care follow-up arrangements
3. Oncological data and planned adjuvant treatment (if appropriate)

3-month data
1. Assessment of complications including re-admission and re-operation if these events occur
2. Information taken from clinical notes and in discussion with each site’s research team
3. Pain Scores electronically self-reported by the patient at 3 months
4. PROMs: Breast-Q reconstruction – satisfaction with information; patient reported complications

18-month data
1. BREAST-Q completed (Reconstruction-pre-operative version)

Added 23/04/2020:
The intervention is prepectoral implant-based breast reconstruction performed according to local surgeons’ standard practice.
This is a multicentre prospective cohort study. The researchers will collect baseline demographic, operative, oncological and complication data at 3 and 18 months. Patients will complete validated patient-reported outcome questionnaires (BREAST-Q) preoperatively and at 3 and 18 months following surgery. Pain scores will be measured using a VAS at 24 hours, 1 week and 3 months.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Current primary outcome measure as of 08/04/2020:
Implant loss rate at 3 months defined as: any unplanned removal of the implant without replacement of the prosthesis (implant or expander) for infection, wound problems or other indication within the first 3 months following surgery

Previous primary outcome measure:
Implant loss rate at 3 months will be determined by clinical review carried out by participating surgeons at participating clinical sites. Implant loss is defined as: "any unplanned removal of the implant without replacement of the prosthesis (implant or expander) for infection, wound problems or other indication within the first 3 months following surgery."

Secondary outcome measures

Current secondary outcome measures as of 08/04/2020:
1. Other key safety measures including infection, return to theatre and reoperation, measured by clinical review at 3 months
2. Post-operative pain scores measured by VAS at 24 hours, 48 hours, 1 week and 3 months
3. Patient satisfaction with the outcome of their reconstruction assessed using the ‘satisfaction with breasts’ domain of the BREAST-Q at 18 months
4. Other patient-reported outcomes included in the breast reconstruction core outcome set including physical function, emotional well being and animation assessed using the BREAST-Q at 18 months
5. The feasibility of using mixed methods to promote shared learning and determine if the procedure is sufficiently stable for evaluation in the context of an RCT
6. The proportion of surgeons reporting modifications/complications; of these
7. The proportion of CRFs including details of modifications or learning arising from complications; of these
8. The proportion of surgeons agreeing to be interviewed; and of these
9. The proportion of interviews performed

Previous secondary outcome measures:
1. Safety will be determined by comparing key safety outcomes for pre-pectoral breast reconstruction including infection; return to theatre and readmission at 3 months with published national audit data. All 3 measures will be determined by clinical teams and reported to the central study team as they occur. Definitions of all 3 measures are:
1.1. Infection- A hot, red swollen breast associated with one of the following; a temperature, pus at the wound site, a raised white cell count and/or; a positive wound swab within the first 3 months following surgery. This will be further classified as:
1.1.1. Minor – requiring oral antibiotics only;
1.1.2. Major 1 – requiring admission for IV antibiotics and/or debridement;
1.1.3. Major 2 – requiring surgical drainage/debridement
1.2. Readmission to hospital– any re-admission to hospital in the 3 months following surgery directly related to the procedure (e.g. with infection requiring antibiotics).
1.3. Return to theatre – Return to the operating theatre at any time during the first 3 months following surgery to deal with any complication of the reconstruction. This will not include any secondary oncological procedures such as axillary clearance or planned procedures including exchange of expander for a fixed volume implant or lipo-modelling.
2. The feasibility of using mixed methods to promote shared learning and identify when the technique is sufficiently stable for evaluation in the context of an RCT will be determined by:
2.1. The number of surgeons reporting modifications to their patient selection criteria or technique, or a post-operative complication via individual patient case report forms (CRFs). Each time one of these events occur, surgeons will be contacted and invited to take part in qualitative interviews to explore these events in further detail. The number of surgeons reporting events via CRFs and agreeing to qualitative interviews will determine the feasibility of these novel methods.
3. The feasibility, design and conduct of a future RCT will be determined by exploring the numbers of patients potentially eligible for pre-pectoral reconstruction; the types and frequencies of products used and approaches to concomitant interventions. This will be measured by:
3.1. Before the study - A national practice survey of both clinical sites and individual surgeons to determine how widely pre-pectoral breast reconstruction (PPBR) is practiced and how widely the technique varies from the point of view of products used and approaches to concomitant interventions (e.g. use of surgical drains and antibiotics) at the start of the study.
3.2. During the study - detailed screening logs will be kept at each clinical site of how many cases are suitable for implant-based breast reconstruction (IBBR), and within this group how many of those would be technically suitable for PPBR? And of those suitable for PPBR, how many go on to have the technique and if they don't choose to, their reasons. This will inform the feasibility of potentially randomising between IBBR and PPBR in a future study.
3.3. At the close of the study - how many surgeons have taken part, what proportion have engaged with qualitative interviews. And how many surgeons report (via individual patient CRFs) that sequential operations they have performed have not been modified i.e. the procedure is stable, and can be evaluated in a randomised controlled trial.
4. The capacity to deliver a future RCT will be determined by the success of 1, 2 and 3

Overall trial start date

01/10/2017

Overall trial end date

28/02/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Consecutive women >16 who require a mastectomy for breast cancer or risk-reduction who:
1. Elect to undergo immediate implant-based breast reconstruction
2. Considered suitable for PPBR by their surgeon
3. Understand and accept that PBRR is innovative and that outcome data are limited

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

341

Participant exclusion criteria

Absolute exclusion criteria:
1. Thin/ insufficiently vascularised skin-flaps as assessed by the operating surgeon
2. Revision /delayed breast reconstruction

Additional relative exclusion criteria applied in line with the ABS/BAPRAS guidelines for mesh-assisted breast reconstruction for surgeons in the learning phase or early practice of prepectoral breast reconstruction:
1. Smokers or ex-smokers <6 weeks
2. Previous radiotherapy to the ipsilateral breast/chest wall
3. BMI >30 (except for dermal sling procedures)
4. Implant size >600cc
5. Anticipated post-mastectomy radiotherapy
6. Poorly controlled diabetes

Recruitment start date

28/05/2019

Recruitment end date

30/09/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

North Bristol NHS Foundation Trust
Southmead Hospital
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Royal Liverpool & Broadgreen University Hospital NHS Trust
Prescot Street
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Pennine Acute Hospitals NHS Trust (Wythenshawe)
North Manchester General Hospital Delaunays Rd Crumpsall
Manchester
M8 5RB
United Kingdom

Trial participating centre

Poole Hospitals NHS Foundation Trust
Longfleet Rd
Poole
BH15 2JB
United Kingdom

Trial participating centre

East Kent Hospitals University NHS Foundation Trust
Ethelbert Rd
Canterbury
CT1 3NG
United Kingdom

Trial participating centre

Cwm Taf Morgannwg University Health Board
Albert Road
Pontypridd
CF37 1LB
United Kingdom

Trial participating centre

Yeovil District Hospital NHS Foundation Trust
Higher Kingston
Yeovil
BA21 4AT
United Kingdom

Trial participating centre

Hywel Dda University Health Board (Prince Phillip)
St Davids Park Jobswell Road
Carmarthen
SA31 3BB
United Kingdom

Trial participating centre

Royal Devon & Exeter NHS Foundation Trust
Barrack Rd
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Tameside and Glossop Integrated Care NHS Foundation Trust
Fountain St
Ashton-Under-Lyne
OL6 9RW
United Kingdom

Trial participating centre

Blackpool Teaching Hospitals NHS Foundation Trust
Whinney Heys Rd
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

Hampshire Hospitals NHS Foundation Trust
Aldermaston Rd
Basington
RG24 9NA
United Kingdom

Trial participating centre

Chesterfield Royal Hospital NHS Foundation Trust
Calow
Chesterfield
S44 5BL
United Kingdom

Trial participating centre

Airedale NHS Foundation Trust
Skipton Rd
Steeton Keighley
BD20 6TD
United Kingdom

Trial participating centre

St George's University Hospital NHS Foundation Trust
Blackshaw Rd Tooting
London
SW17 0QT
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Derby Rd
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

North Tees and Hartlepool NHS Foundation Trust
Holdforth Rd
Hartlepool
TS24 9AH
United Kingdom

Trial participating centre

Bradford Teaching Hospital NHS Foundation Trust
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Wrightington, Wigan and Leigh NHS Foundation Trust
The Elms Wigan Lane
Wigan
WN1 2NN
United Kingdom

Trial participating centre

Frimley Health NHS Foundation Trust (Wexham Park)
Portsmouth Road
Frimley
GU16 7UJ
United Kingdom

Trial participating centre

St Helens and Knowsley Teaching Hospitals NHS Trust
Warrington Rd
Prescot
L35 5DR
United Kingdom

Trial participating centre

The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

Royal Berkshire NHS Foundation Trust (Reading)
London Road
Reading
RG1 5AN
United Kingdom

Trial participating centre

Bolton NHS Foundation Trust
Minerva Rd Farnworth
Bolton
BL4 0JR
United Kingdom

Trial participating centre

The Royal Wolverhampton NHS Trust
New Cross Hospital Wolverhampton Rd Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

North West Anglia NHS Foundation Trust
Bretton Gate Bretton
Peterborough
PE3 9GZ
United Kingdom

Trial participating centre

The Oxford University Hospitals NHS Foundation Trust
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Norfolk and Norwich University Hospitals NHS Foundation Trust
Colney Lane Colney
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
Cobbet House Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Wirral University Teaching Hospital NHS Foundation Trust
Arrowe Park Hospital Arrowe Park Road
Upton
CH49 5PE
United Kingdom

Trial participating centre

Western Sussex Hospitals NHS Foundation Trust
Worthing Hospital Lyndhurst Rd
Worthing
BN11 2DH
United Kingdom

Trial participating centre

Brighton & Sussex University Hospitals NHS Trust
Eastern Rd
Brighton
BN2 5BE
United Kingdom

Trial participating centre

The Dudley Group NHS Foundation Trust
Russells Hall Hospital Pensnett Rd
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
St. James's University Hospital Beckett St
Leeds
LS9 7TF
United Kingdom

Trial participating centre

East Suffolk and North Essex NHS Foundation Trust
Turner Road
Colchester
CO4 5JL
United Kingdom

Trial participating centre

Grampian Health Board
2 Eday Rd
Aberdeen
AB15 6RE
United Kingdom

Trial participating centre

NHS Forth Valley
33 Spittal St
Stirling
FK8 1DX
United Kingdom

Sponsor information

Organisation

University of Bristol

Sponsor details

Senate House
Tyndall Ave
Bristol
BS8 1TH
United Kingdom
+44 (0)1174284011
research.governance@bristol.ac.uk

Sponsor type

University/education

Website

http://www.bristol.ac.uk/red/research-governance/

Funders

Funder type

Charity

Funder name

Royal College of Surgeons of England

Alternative name(s)

RCS

Funding Body Type

private sector organisation

Funding Body Subtype

Associations and societies (private and public)

Location

United Kingdom

Funder name

The Association of Breast Surgeons

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The NIHR Bristol Biomedical Research Centre Director's Fund

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Results will be published and presented at national and international meetings and in a peer-reviewed journal.

Added 09/04/2020:
Primary outcome results publication: 07/2021
Results and PROMs publication: 30/12/2022

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/12/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2020 protocol in https://www.ncbi.nlm.nih.gov/pubmed/31988232 (added 09/04/2020)

Publication citations

Additional files

Editorial Notes

13/07/2020: The recruitment end date was changed from 30/06/2020 to 30/09/2020. 23/04/2020: The following changes were made to the trial record: 1. The interventions field was updated. 2. 37 trial participating centres were added. 09/04/2020: The following changes were made to the trial record: 1. Publication reference added. 2. Publication and dissemination plan, contact details updated. 08/04/2020: The following changes were made to the trial record: 1. Contact and sponsor details, study hypothesis, ethics approval, primary and secondary outcome measures updated. 2. The protocol/serial number was changed from 1.0 to 2.0. 3. The recruitment start date was changed from 03/06/2019 to 28/05/2019. 4. The recruitment end date was changed from 02/06/2020 to 30/06/2020. 5. The overall trial end date was changed from 01/04/2021 to 28/02/2022. 6. The intention to publish date was changed from 01/12/2020 to 30/12/2022. 05/07/2019: The ethics approval was added. 07/06/2019: Internal review. 10/05/2019: Internal review.