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Trial registered on ANZCTR


Trial ID
ACTRN12616000969460
Ethics application status
Approved
Date submitted
12/07/2016
Date registered
22/07/2016
Date last updated
26/04/2018
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] 289649 0
None
Universal Trial Number (UTN)
None
Trial acronym
CROSSFIRE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Distal radius fractures 299448 0
Condition category
Condition code
Musculoskeletal 299429 299429 0 0
Other muscular and skeletal disorders
Injuries and Accidents 299538 299538 0 0
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] 295271 0
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] 298896 0
Patient reported wrist evaluation (PRWE) score at 12 months post treatment
Timepoint [1] 298896 0
12 months post treatment
Secondary outcome [1] 325566 0
PRWE at 3 months, 2, 5 and 10 years post treatment
Timepoint [1] 325566 0
3 months, 2, 5 and 10 years post treatment
Secondary outcome [2] 325567 0
Disability of the Arm Shoulder and Hand (DASH) at 12 months
Timepoint [2] 325567 0
12 months, post treatment
Secondary outcome [3] 325568 0
EQ5D (5L) (Health related quality of life) at baseline, 3 and 12 months and 2, 5 and 10 years, post treatment
Timepoint [3] 325568 0
Baseline, 3 and 12 months and 2, 5 and 10 years, post treatment
Secondary outcome [4] 325569 0
Pain (numerical rating scale NRS, 0-10) at 3 and 12 months and 2, 5 and 10 years post treatment
Timepoint [4] 325569 0
3 and 12 months and 2, 5 and 10 years post treatment
Secondary outcome [5] 325570 0
Patient reported treatment success (at 12 months, 5-point Likert scale)
Timepoint [5] 325570 0
at 12 months post treatment
Secondary outcome [6] 325571 0
Patient rated bother with appearance (at 12 month and 2, 5 and 10 years, 5-point Likert scale)
Timepoint [6] 325571 0
12 month and 2, 5 and 10 years post treatment
Secondary outcome [7] 325572 0
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] 325572 0
3 months, 6 months, 12 months, 2, 5 and 10 years post treatment
Secondary outcome [8] 325573 0
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] 325573 0
repeat Xray at surgical review, typically at 6 weeks but anywhere up to 12 months post treatment
Secondary outcome [9] 325574 0
The participant is asked about therapy utilisation up to and at 3 months post treatment at their three-month follow-up
Timepoint [9] 325574 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 8022 0
New Zealand
State/province [1] 8022 0
Wellington

Funding & Sponsors
Funding source category [1] 294049 0
Government body
Name [1] 294049 0
NHMRC
Address [1] 294049 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 294049 0
Australia
Funding source category [2] 296436 0
Charities/Societies/Foundations
Name [2] 296436 0
AOA Research Foundation
Address [2] 296436 0
Australian Orthopaedic Association, Level 12, 45 Clarence St, Sydney, NSW, Australia, 2000
Country [2] 296436 0
Australia
Funding source category [3] 296437 0
Charities/Societies/Foundations
Name [3] 296437 0
AO Trauma Asia Pacific
Address [3] 296437 0
AO Asia Pacific Ltd.
Unit 1310-11 Tower 1,
Millennium City 1,
388 Kwun Tong Road,
Kowloon, Hong Kong
Country [3] 296437 0
Hong Kong
Funding source category [4] 296438 0
Charities/Societies/Foundations
Name [4] 296438 0
The Lincoln Centre for Research into Bone and Joint Diseases
Address [4] 296438 0
Kolling Institute of Medical Research
Royal North Shore Hospital, Pacific Hwy, St Leonards NSW 2065
Country [4] 296438 0
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] 292873 0
None
Name [1] 292873 0
Address [1] 292873 0
Country [1] 292873 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295462 0
Hunter New England Research Ethics & Governance Office
Ethics committee address [1] 295462 0
Hunter New England Research Ethics & Governance Office
Locked Bag No 1
New Lambton NSW 2305
Ethics committee country [1] 295462 0
Australia
Date submitted for ethics approval [1] 295462 0
17/02/2016
Approval date [1] 295462 0
11/07/2016
Ethics approval number [1] 295462 0
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 [4] 2632 2632 0 0

Contacts
Principal investigator
Name 67330 0
Prof Ian Harris
Address 67330 0
Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Level 2, 1 Campbell St, Liverpool, 2170, NSW, Australia.
Country 67330 0
Australia
Phone 67330 0
+61 2 8738 9254
Fax 67330 0
+61 2 9602 7187
Email 67330 0
iaharris1@gmail.com
Contact person for public queries
Name 67331 0
Mr Andrew Lawson
Address 67331 0
Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Level 2, 1 Campbell St, Liverpool, 2170, NSW, Australia.
Country 67331 0
Australia
Phone 67331 0
+61 2 8738 9254
Fax 67331 0
+61 2 9602 7187
Email 67331 0
aalawson@tpg.com.au
Contact person for scientific queries
Name 67332 0
Mr Andrew Lawson
Address 67332 0
Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, UNSW Australia
Level 2, 1 Campbell St, Liverpool, 2170, NSW, Australia.
Country 67332 0
Australia
Phone 67332 0
+61 2 8738 9254
Fax 67332 0
+61 2 9602 7187
Email 67332 0
aalawson@tpg.com.au