ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616000969460

Ethics application status

Approved

Date submitted

12/07/2016

Date registered

22/07/2016

Date last updated

22/04/2020

Date data sharing statement initially provided

29/04/2019

Date results information initially provided

29/04/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

CROSSFIRE - Evaluation of surgical fixation versus conservative management for distal radius fractures in the elderly.

Scientific title

A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly

Secondary ID [1]

None

Universal Trial Number (UTN)

None

Trial acronym

CROSSFIRE

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Distal radius fractures

Condition category

Condition code

Musculoskeletal

Other muscular and skeletal disorders

Injuries and Accidents

Fractures

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention group (plate group)
Surgical fixation using a volar locking plate will be performed within two weeks of initial injury according to usual care of the participating institution, with an orthopaedic surgeon in attendance. This is a commonly performed procedure and it takes about one hour. Surgical technique and type of plate (make and length) will be surgeon preference. A plaster cast may be applied post operatively but for no longer than two weeks. Active finger movement will be encouraged post operatively. Participants will be reviewed 2 weeks (10-17 days) after surgery; the wound will be reviewed and sutures removed where necessary. Participants will be provided with a home-exercise program (written information) post-operatively. The home exercise programme will include four simple wrist range of motion exercises, to be performed three times daily for four weeks following the two-week review. Referral for outpatient rehabilitation will not be routinely provided but will be permitted.

Intervention code [1]

Treatment: Surgery

Comparator / control treatment

Participants in this group will be treated with a closed reduction and cast immobilisation, avoiding wrist flexion, within two weeks of the initial injury. This method of casting is consistent with standard casting practice in Australia. Immobilisation of a DRF in flexion has been associated with an increased risk of fracture displacement as well as finger and MCPJ stiffness. Also, immobilisation in a cast that is too restrictive and excessively flexed has been associated with an increased risk of CRPS.
The reduction may be performed in the Emergency Department under sedation and local anaesthetic infiltration into the fracture (haematoma block) where possible, but may also be performed in an operating room (according to availability and local practice). The procedure will be performed by an orthopaedic surgeon or registrar. Post reduction radiographs will be taken to assess the fracture alignment after the reduction. The best reduction achievable will be accepted.
The cast will be removed at six (+/-1) weeks from the initial reduction. Active finger movement and light use of the hand will be encouraged immediately. Participants will be provided with a home-exercise program (written information). The home exercise programme will include four simple wrist range of motion exercises, to be performed three times daily for four weeks following the two-week review. Referral for outpatient rehabilitation will not be routinely provided but will be permitted.

Control group

Active

Outcomes

Primary outcome [1]

Patient reported wrist evaluation (PRWE) score at 12 months post treatment

Timepoint [1]

12 months post treatment

Secondary outcome [1]

PRWE at 3 months, 2, 5 and 10 years post treatment

Timepoint [1]

3 months, 2, 5 and 10 years post treatment

Secondary outcome [2]

Disability of the Arm Shoulder and Hand (DASH) at 12 months

Timepoint [2]

12 months, post treatment

Secondary outcome [3]

EQ5D (5L) (Health related quality of life) at baseline, 3 and 12 months and 2, 5 and 10 years, post treatment

Timepoint [3]

Baseline, 3 and 12 months and 2, 5 and 10 years, post treatment

Secondary outcome [4]

Pain (numerical rating scale NRS, 0-10) at 3 and 12 months and 2, 5 and 10 years post treatment

Timepoint [4]

3 and 12 months and 2, 5 and 10 years post treatment

Secondary outcome [5]

Patient reported treatment success (at 12 months, 5-point Likert scale)

Timepoint [5]

at 12 months post treatment

Secondary outcome [6]

Patient rated bother with appearance (at 12 month and 2, 5 and 10 years, 5-point Likert scale)

Timepoint [6]

12 month and 2, 5 and 10 years post treatment

Secondary outcome [7]

Complications (deep infection, reoperation, neuropathy, tendon irritation requiring treatment, tendon rupture, fracture non-union at minimum 6 months, implant failure, complex regional pain syndrome, death) at 3 months, 12 months, 2, 5 and 10 years. Complications will be assessed for at regular post-surgical reviews as per usual care.

Timepoint [7]

3 months, 6 months, 12 months, 2, 5 and 10 years post treatment

Secondary outcome [8]

Radiographic measures (any or all of shortening [ulnar variance], dorsal angulation [relative to radial shaft], articular step-off) measured at presentation, post reduction, and with repeat Xray at surgical review between 6 weeks and 12 months)

Timepoint [8]

repeat Xray at surgical review, typically at 6 weeks but anywhere up to 12 months post treatment

Secondary outcome [9]

The participant is asked about therapy utilisation up to and at 3 months post treatment at their three-month follow-up

Timepoint [9]

3 months post treatment

Eligibility

Key inclusion criteria

* Age 60 years or older
* Displaced distal radius fracture (AO/OTA 23A or 23C with more than 10 degrees dorsal angulation, referenced off a line perpendicular to the shaft of the radius or more than 3mm shortening or more than 2mm articular step) prior to reduction
* Medically fit for surgery
* Independent living (including hostel accommodation)
* Isolated injury
* Low energy injury (fall from less than 1m)
* Available for follow up for 12 months
* The injury must have occurred within one week of enrolment into the study

Minimum age

60 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* Patient unable to provide consent (due to cognitive capacity or English proficiency)
* Volar angulation
* Diaphyseal extension
* Partial articular fractures eg chauffer, Barton’s (AO/OTA 23B)
* Associated fracture or dislocation in any other body part that will affect the use of the involved wrist (ulna styloid fracture will be permitted, as these are usually associated with the fracture under investigation)
* Open injury
* Previous wrist fracture on the same side
* Medical condition precluding anaesthetic

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Due to the nature of the comparisons (surgery versus no surgery), it will not be possible to blind the surgeon (study) investigators or participants. While this may render the trial at risk of performance and detection bias, every effort will be made to ensure that treatment, other than the interventions under study is identical in both groups. The primary outcome (PRWE – patient rated wrist evaluation score at 12 months) will be collected from participants by blinded researchers, by telephone. The statistician will be blinded to the treatment group. Participating surgeons have equipoise regarding the two treatment alternatives

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Participants will be randomised using the method of minimisation. Randomisation will be stratified by site, and minimisation, adjusting for gender and age (60-74 years and >74 years), will be employed as recommended by the NHMRC Clinical Trials Centre who will provide the randomisation service. Minimisation (adaptive stratified sampling) aims to reduce imbalance between the groups on prognostic factors which can occur despite random allocation of treatment. Here, age and gender will be included in the minimisation algorithm for randomisation.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Parallel observational group; Patients who do not consent to be randomised will be offered participation in the observational arm of the study. Their treatment will consist of either closed reduction and cast immobilisation or operative fixation using a volar locking plate (the same two treatment options as the RCT arm). Treatment will be decided by patient preference as per usual practice at each institution. Post-operative treatment protocols, follow up and outcome measures will be the same as the randomised arms.

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Data analysis: The primary outcome is the PRWE score at 12 months. An analysis of covariance will be used to compare the mean PRWE between the two independent groups. Intention to treat analysis will be performed in the primary analysis. A per-protocol analysis (including participants according to treatment received) will be added as a secondary analysis. Analysis of secondary outcomes will include mixed model analyses, comparing secondary outcomes between timepoints. Non-operative treatment will be defined as a minimum of 28 days in the plaster splint for the purposes of the per-protocol analysis.
The observational cohort will be analysed separately, comparing the same two treatment groups against the same outcomes using multivariable linear regression to adjust for potential confounders. Repeated measures analysis will be performed as a secondary analysis.
Attempts will be made to minimise missing data, such as obtaining multiple contact details at recruitment and using telephone follow up rather than mail. Missing data will be dealt with according to the instructions on the use of the outcome tools (PRWE, DASH and EQ-5D-5L). If greater than ten percent of data is missing from the randomised sample, then missing data will be imputed.
Sample size; The recent RCT by Arora et al [2011] used a 1:1 allocation, 5% significance and 80% power to detect a difference of 10 points on the PRWE, calculating a sample size of 68 participants for both groups. Based on a standard deviation (SD) for the PRWE of 23 in the Arora study, a 10-point threshold would be less than the commonly used threshold of 0.5SD for a clinically important difference [Norman, Sloan and Wyrwich, 2003] and less than the MCID of 12 points for the PRWE determined by Walenkamp et al [2015]. Using a 14-point cut off represents 0.6SD and is in line with another estimate of the minimum clinically important difference of the PRWE [Sorensen et al, 2013]. We consider 14 points to be the minimum clinical difference necessary to justify the additional costs of surgery compared to non-operative treatment.
A total of 128 patients (64 in each group) will provide 90% power to detect a difference of 14 points on the PRWE scale at a significance level of 0.05. We aim to recruit 160 patients to allow for 20% loss to follow up. The previous RCTs each reported loss to follow up rates of 19% [Arora et al, 2011, Bartl et al, 2014].
The observational cohort will be a convenience sample of patients not consenting to randomisation. In our experience, this group will comprise approximately two participants for every one randomised. We will therefore recruit 160 patients into the randomised trial and approximately 300 patients into the parallel observational cohort.

Arora, R., et al., A prospective randomized trial comparing nonoperative treatment with volar locking plate fixation for displaced and unstable distal radial fractures in patients sixty-five years of age and older. J Bone Jt Surg (Am), 2011. 93(23): 2146-53.

Bartl, C., Stengel, D., Bruckner, T., Gebhard, F., The Treatment of Displaced Intra-articular Distal Radius Fractures in Elderly Patients: A Randomized Multi-center Study (ORCHID) of Open Reduction and Volar Locking Plate Fixation Versus Closed Reduction and Cast Immobilization. Dtsch Arztebl International, 2014. 111(46): 779-87.

Norman, G.R., J.A. Sloan, and K.W. Wyrwich, Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care, 2003. 41(5): 582-92.

Walenkamp, M.M.J., et al., The Minimum Clinically Important Difference of the Patient-rated Wrist Evaluation Score for Patients With Distal Radius Fractures. Clin Orthop Relat Res (2015) 473:3235–3241.

Sorensen, A.A., et al., Minimal clinically important differences of 3 patient-rated outcomes instruments. J Hand Surg Am, 2013. 38(4): 641-9.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

1/08/2016

Actual

4/10/2016

Date of last participant enrolment

Anticipated

31/12/2018

Actual

8/01/2019

Date of last data collection

Anticipated

8/01/2029

Actual

Sample size

Target

450

Accrual to date

Final

301

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,TAS,WA,VIC

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Wellington

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

AOA Research Foundation

Address [2]

Australian Orthopaedic Association, Level 12, 45 Clarence St, Sydney, NSW, Australia, 2000

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

AO Trauma Asia Pacific

Address [3]

AO Asia Pacific Ltd.
Unit 1310-11 Tower 1,
Millennium City 1,
388 Kwun Tong Road,
Kowloon, Hong Kong

Country [3]

Hong Kong

Funding source category [4]

Charities/Societies/Foundations

Name [4]

The Lincoln Centre for Research into Bone and Joint Diseases

Address [4]

Kolling Institute of Medical Research
Royal North Shore Hospital, Pacific Hwy, St Leonards NSW 2065

Country [4]

Australia

Primary sponsor type

University

Name

Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia

Address

Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Locked Bag 7103, Liverpool BC 1871, NSW, Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England Research Ethics & Governance Office

Ethics committee address [1]

Hunter New England Research Ethics & Governance Office
Locked Bag No 1
New Lambton NSW 2305

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/02/2016

Approval date [1]

11/07/2016

Ethics approval number [1]

HREC/16/HNE/10

Summary

Brief summary

Fractures of the distal radius are the most common fractures presenting to emergency departments and orthopaedic surgeons. These fractures are more common in the elderly (due to osteoporosis and increased risk of falls) and the incidence in this age group is increasing. Considerable practice variation exists in the management of distal radius fractures in the elderly in Australia, ranging from closed reduction (manipulation of the arm to realign the fracture) with cast immobilisation, to open reduction (surgical exposure and realignment of the fracture) with plate fixation. Open reduction and (volar locking) plate fixation is currently the most common treatment provided. While there is evidence showing no significant advantage for some forms of surgical fixation over closed treatment, and no difference between different surgical techniques, there is a lack of evidence comparing the two most common treatments used in Australia: volar locked plate fixation versus cast immobilisation. Surgical management of these fractures involves significant costs (implant costs, medical costs, hospital costs) and risks (infection, implant failure, general surgical risks) compared to non-operative management (closed reduction and cast immobilisation in the emergency department). Therefore, high level evidence comparing the current treatment alternatives (plate fixation versus casting) is required in order to address practice variation, justify or avoid costs, and to provide the best clinical outcome for patients with these common fractures.
This pragmatic, multicentre randomised comparative effectiveness trial aims to determine whether (volar locking) plate fixation leads to better pain and function and is more cost-effective than closed reduction with cast immobilisation in displaced distal radius fractures in adults aged 60 years and older. The trial will compare the two techniques, but will also follow patients that are unwilling to be randomised (but consent to follow up) in a separate, observational arm. Inclusion of non-randomised patients provides a more complete spectrum of fracture presentation, provides practice and outcome insights about standard care, and improves the generalisation of the results from the randomised arms.
Given that plate fixation requires hospital admission and surgery, and that closed reduction with cast immobilisation is usually performed in the emergency department without admission, the findings have important implications for use of resources (theatre time, bed days, staff and implant costs) and may also reduce harms associated with plate fixation (infection, implant mal-positioning, tendon rupture and reoperation for implant removal). This trial will have significance in Australia, New Zealand and internationally, as it will address an important need for evidence supporting surgical practice.

Trial website

http://www.crossfireproject.com/

Trial related presentations / publications

Harris IA, Naylor JM, Lawson A, et al. A combined randomised and observational study of surgery for fractures in the distal radius in the elderly (CROSSFIRE)—a study protocol. BMJ Open 2017;7:e016100. doi: 10.1136/bmjopen-2017-016100

Public notes

Attachments [1]

/AnzctrAttachments/371068-1602173.04 Variationapproval - clinical trial MS.pdf

Attachments [2]

/AnzctrAttachments/371068-1602173.04 Approval Clinical Trial Multi-site LeadHREC.pdf

Attachments [3]

/AnzctrAttachments/371068(v12-07-2016-23-11-08)-CROSSFIRE v20.docx (Protocol)

Attachments [4]

/AnzctrAttachments/371068-CROSSFIRE v24 (clean).pdf (Protocol)

Contacts

Principal investigator

Name

Prof Ian Harris

Address

Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Level 2, 1 Campbell St, Liverpool, 2170, NSW, Australia.

Country

Australia

Phone

+61 2 8738 9254

Fax

+61 2 9602 7187

[email protected]

Contact person for public queries

Name

Mr Andrew Lawson

Address

Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Level 2, 1 Campbell St, Liverpool, 2170, NSW, Australia.

Country

Australia

Phone

+61 2 8738 9254

Fax

+61 2 9602 7187

[email protected]

Contact person for scientific queries

Name

Mr Andrew Lawson

Address

Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Level 2, 1 Campbell St, Liverpool, 2170, NSW, Australia.

Country

Australia

Phone

+61 2 8738 9254

Fax

+61 2 9602 7187

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

We have not determined a plan for data sharing at this stage

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
1899	Study protocol				https://bmjopen.bmj.com/content/7/6/e016100

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Surgical plating versus closed reduction for fractures in the distal radius in older patients: a cost-effectiveness analysis from the hospital perspective.	2022	https://dx.doi.org/10.1111/ans.18134
Embase	Plating vs Closed Reduction for Fractures in the Distal Radius in Older Patients: A Secondary Analysis of a Randomized Clinical Trial.	2022	https://dx.doi.org/10.1001/jamasurg.2022.0809
Embase	A combined randomised and observational study of surgery for fractures in the distal radius in the elderly (CROSSFIRE) - A study protocol.	2017	https://dx.doi.org/10.1136/bmjopen-2017-016100
Embase	A Combined Randomised and Observational Study of Surgery for Fractures in the distal Radius in the Elderly (CROSSFIRE): A statistical analyses plan.	2020	https://dx.doi.org/10.1186/s13063-020-4228-0
Embase	Surgical Plating vs Closed Reduction for Fractures in the Distal Radius in Older Patients: A Randomized Clinical Trial.	2021	https://dx.doi.org/10.1001/jamasurg.2020.5672

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically