Condition category
Injury, Occupational Diseases, Poisoning
Date applied
25/03/2008
Date assigned
25/03/2008
Last edited
27/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Fractures of the proximal humerus (the top part of the upper arm bone) are very common, particularly in older adults who have weaker bones (osteoporotic). The treatment for this type of fracture can vary, depending on how serious it is. Generally, less serious fractures are successfully treated by supporting the injured arm in a sling until the fracture mends (immobilization). If the fracture is more serious however, such as in cases where the bone has broken into two or more pieces which are out of alignment (displaced) then surgery may be a more appropriate option. Despite this little is known about whether surgical or non-surgical treatment is best for the more common types of displaced fracture. The aim of this study is to investigate the effectiveness and cost-effectiveness of surgical and non-surgical treatments for displaced fractures of proximal humerus.

Who can participate?
Patients aged 16 or over who have fractured the top of their upper arm bone in the past 3 weeks.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group have their fracture treated surgically, either using plate fixation (where the fracture is held together by a metal plate that is screwed to the bone on either side) or joint replacement (where the damaged joint is removed and replaced with a man-made one). It is left up to the surgeon to judge which procedure is more appropriate for each individual participant. Those in the second group have their fracture treated using a sling that they wear for around 3 weeks, which is designed to hold the arm in place so that the fracture can heal. After 6, 12 and 24 months, participants in both groups complete a number of questionnaires in order to find out how well their fracture has healed and to identify any complications they have suffered.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
James Cook University Hospital, Middlesbrough (UK)

When is the study starting and how long is it expected to run for?
October 2008 to August 2016

Who is funding the study?
National Institute for Health Research, Health Technology Assessment Programme (UK)

Who is the main contact?
Professor Amar Rangan
amar.rangan@york.ac.uk

Trial website

www.york.ac.uk/healthsciences/research/trials/research/trials/profher/

Contact information

Type

Scientific

Primary contact

Prof Amar Rangan

ORCID ID

Contact details

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
+44 (0)1642 854380
amar.rangan@york.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 06/404/53

Study information

Scientific title

Pragmatic multi-centre randomised trial of surgical versus non-surgical treatment for proximal fracture of the humerus in adults

Acronym

PROFHER

Study hypothesis

To assess the effectiveness and cost-effectiveness of surgical versus non-surgical treatment of the majority of displaced proximal humeral fractures in adults.

Protocols can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0015/51423/PRO-06-404-53.pdf
More information can be found at http://www.nets.nihr.ac.uk/projects/hta/0640453

Following the completion of recruitment, it was agreed to obtain 3, 4 and 5 year data on key outcomes in order to determine whether there is any persistence or alteration of the treatment effect detected at 2 year follow-up. Secondary aims are to:
1. Obtain longer term condition specific data on shoulder function using validated instruments (OSS, EQ-5D) that will provide reference data for informing the interpretation of the findings of ProFHER and future studies of proximal humeral fractures
2. Inform future research in this area on the appropriate duration of follow-up

Ethics approval

York Multi-centre Research Ethics Committee (MREC), 11/03/2008, ref: 08/H1311/12
The long term study was approved as a substantial amendment by Leeds West Research Ethics Committee on 22/09/2010.

Study design

Multi-centre randomised controlled trial

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 below to request a patient information sheet

Condition

Musculoskeletal trauma of the upper limb

Intervention

Interventions as of 18/10/2016:
After obtaining informed consent and key baseline information, research associates will randomly allocate patients to surgical or non-surgical treatment using an independent remote randomization service (telephone or online access) provided by the York Trials Unit (University of York). Randomization will be performed using a computer program with 1:1 allocation, stratifying by tuberosity involvement (yes or no) and using random block sizes of 4, 8, and 12. Originally after a prespecified period minimisation was to be introduced based on whether fractures involved either tuberosity and centre but was abandoned because of the small number of patients at a hospital site.

Surgical group: Participants allocated to surgery will receive either internal fracture fixation (e.g., with plate and screws) to preserve the humeral head or humeral head replacement (hemiarthroplasty).

Non-surgical group: Participants allocated to non-surgical treatment will be given a sling for the injured arm for as long as deemed necessary (3 weeks will be suggested), followed by active rehabilitation. Delivery of care and rehabilitation, which will be freely available for all patients, incorporated the following 3 set measures to ensure good standards of care within the National Health Service: provision of an information leaflet on personal care during sling immobilization; a basic treatment protocol to guide physiotherapy; and promotion of home exercises. Rehabilitation care will be provided by physiotherapists in inpatient, outpatient, and community settings.

Participants in both groups complete a range of questionnaires and assessments at 3, 6, 12 and 24 months, and then after 3, 4 and 5 years.

Original interventions:
Participants will be randomised to one of two basic treatment interventions:
1. Surgery (fixation or joint replacement)
2. Non-surgical management (sling immobilisation)

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Oxford Shoulder Score (12-item condition-specific questionnaire providing a total score based on the person's subjective assessment of pain and activities of daily living impairment) assessed at 6, 12 and 24 months and 3, 4 and 5 years via postal questionnaire.

Secondary outcome measures

1. General health status is measured using The 12-item short form health survey (SF-12) at 6, 12 and 24 months and Euroqol (EQ-5D) at 3, 6, 12 and 24 months and 3, 4 and 5 years
2. Complications, including surgical complications (wound infection, implant failure, shoulder dislocation, septicaemia) are assessed via medical record review at the end of an in-patient episode at the start of the trial and at 1 and 2 year hospital follow-up
3. Early medical complications, i.e. chest infection, confirmed myocardial infarction or stroke, treated deep vein thrombosis and pulmonary embolism are assessed via medical record review at the end of an in-patient episode at the start of the trial and other medical complications at 1 and 2 year hospital follow-up
4. Mortality rate is assessed via medical review continuously for 2 years
5. Subsequent referral for operation or substantive treatment is assessed via medical record review at 1 and 2 year hospital follow-up and then at 3, 4 and 5 year follow ups via postal questionnaire
6. NHS and societal costs are collected at 3, 6, 12 and 24 months via postal questionnaire and hospital forms: surgical form, physiotherapy form, inpatient episode form and 1 and 2 year hospital follow-up forms

Overall trial start date

01/10/2008

Overall trial end date

12/08/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 16 or above, male and female
2. Presenting to the participating trauma centre within 3 weeks of their injury
3. Radiologically confirmed displaced fracture of the proximal humerus involving the surgical neck
4. Surgeon would consider surgical treatment for the fracture

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

250

Participant exclusion criteria

1. Open fracture
2. Cognitive impairment that would preclude participation
3. Co-morbidities precluding surgery/ anaesthesia
4. Clear indication for surgery such as severe soft-tissue compromise requiring surgery/ emergency treatment
5. Multiple injuries: Same limb fractures, other upper limb fractures
6. Pathological fractures (other than osteoporotic)
7. Terminal illness
8. Participant not resident in trauma-centre catchment area

Recruitment start date

01/10/2008

Recruitment end date

28/02/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

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

Sponsor information

Organisation

Teesside University

Sponsor details

Clarendon Road
Middlesbrough
TS1 3BA
United Kingdom

Sponsor type

University/education

Website

http://www.tees.ac.uk

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in peer reviewed journals.

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

Intention to publish date

30/06/2015

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

2009 protocol in http://www.ncbi.nlm.nih.gov/pubmed/19917097
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/25519445
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/25756440
2015 results in http://www.ncbi.nlm.nih.gov/pubmed/25822598
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/26549433
2016 results in http://www.ncbi.nlm.nih.gov/pubmed/26850418
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27756739

Publication citations

  1. Protocol

    Handoll H, Brealey S, Rangan A, Torgerson D, Dennis L, Armstrong A, Chuang LH, Cross B, Dumville J, Gardner S, Goodchild L, Hamilton S, Hewitt C, Madhok R, Maffulli N, Micklewright L, Wadsworth V, Wallace A, Williams J, Worthy G, Protocol for the ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial: a pragmatic multi-centre randomised controlled trial of surgical versus non-surgical treatment for proximal fracture of the humerus in adults., BMC Musculoskelet Disord, 2009, 10, 140, doi: 10.1186/1471-2474-10-140.

  2. Results

    Rangan A, Handoll H, Brealey S, Jefferson L, Keding A, Martin BC, Goodchild L, Chuang LH, Hewitt C, Torgerson D; PROFHER Trial Collaborators, Surgical vs Nonsurgical Treatment of Adults With Displaced Fractures of the Proximal Humerus: The PROFHER Randomized Clinical Trial, JAMA, 2015 , 313, 10, 1037-1047, doi: 10.1001/jama.2015.1629.

  3. Results

    Handoll H, Brealey S, Rangan A, Keding A, Corbacho B, Jefferson L, Chuang LH, Goodchild L, Hewitt C, Torgerson D, The ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial - a pragmatic multicentre randomised controlled trial evaluating the clinical effectiveness and cost-effectiveness of surgical compared with non-surgical treatment for proximal fracture of the humerus in adults, Health Technol Assess, 2015, 19, 24, 1-280.

  4. Results

    Corbacho B, Duarte A, Keding A, Handoll H, Chuang LH, Torgerson D, Brealey S, Jefferson L, Hewitt C, Rangan A, Cost effectiveness of surgical versus non-surgical treatment of adults with displaced fractures of the proximal humerus: economic evaluation alongside the PROFHER trial, The Bone & Joint Journal, 2016, 98-B, 2, 152-159, doi: 10.1302/0301-620X.98B2.36614.

  5. Results

    Jefferson L, Cook L, Keding A, Brealey S, Handoll H, Rangan A, 'Away Days' in multi-centre randomised controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment, J Evid Based Med, 2015, doi: 10.1111/jebm.12180.

  6. Results

    Handoll HH, Brealey SD, Jefferson L, Keding A, Brooksbank AJ, Johnstone AJ, Candal-Couto JJ, Rangan A. , Defining the fracture population in a pragmatic multicentre randomised controlled trial: PROFHER and the Neer classification of proximal humeral fractures, Bone Joint Res, 2016, 5, 10, 481-489.

  7. Results

    Handoll HH, Goodchild L, Brealey SD, Hanchard NC, Jefferson L, Keding A, Rangan A., Developing, delivering and documenting rehabilitation in a multi-centre randomised controlled surgical trial: experiences from the ProFHER trial, Bone Joint Res, 2014, 3, 12, 335-340.

Additional files

Editorial Notes

26/10/2016: Publication reference added. 18/10/2016: Following the completion of recruitment, it was agreed to obtain 3, 4 and 5 year data on key outcomes in order to determine whether there is any persistence or alteration of the treatment effect detected at 2 year follow-up. In light of this, the following updates have been made to the record: 1. The overall trial end date has been changed from 28/02/2014 to 12/08/2016 2. Additional tiomepoints of measurement (3, 4 and 5 years have been added to a number of outcome measures 3. The interventions section has been updated to include further detail and details of the extended follow up 4. The ethics approval section has been updated to show when the long term follow up was approved. 09/03/2016: Publication reference added. 04/02/2016: Plain English summary added. 15/02/2012: The overall trial end date was changed from 30/09/2012 to 28/02/2014.