Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000214437p
Ethics application status
Not yet submitted
Date submitted
7/02/2016
Date registered
17/02/2016
Date last updated
17/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Is Platelet-Rich Plasma (PRP) superior to dry needling prolotherapy for promoting recovery in rugby players with ankle syndesmosis injury?
Scientific title
Effectiveness of PRP for promoting recovery from ankle syndesmosis injury in rugby- a double-blinded, randomised controlled trial.
Secondary ID [1] 288493 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ankle syndesmosis injury 297553 0
Condition category
Condition code
Musculoskeletal 297755 297755 0 0
Other muscular and skeletal disorders
Injuries and Accidents 297804 297804 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single platelet rich plasma injection into the Antero-inferior tibiofibular ligament (AITFL) of the ankle will be administered within 14 days of injury.
1-2mL of 2% lignocaine will be infiltrated to the skin and superficial tissues. Blood will be drawn and centrifuged at 3000RPM for 8 minutes. The PRP will be manually aspirated. 0.5-1mL of PRP will be injected with a 25 guage needle into the defect of the AITFL seen on ultrasound in the intervention group. The exact volume will be individualised and recorded, to minimise hydrodissection of the injured tissue by excessive volume injected.
All injections will be performed by radiologist Dr James Linklater (JL) at Castlereagh Imaging St Leonards, Sydney.
After the intervention, participants will be given oral analgesia, and record a one week pain score and this will have the primary investigators contact details should there be any concerns.
Intervention code [1] 293853 0
Treatment: Other
Comparator / control treatment
A single administration of dry needling under ultrasound guidance using a peppering technique (to achieve a prolotherapy effect) will occur within 14 days of injury.
1-2mL of 2% lignocaine will be infiltrated to the skin and superficial tissues. Blood will be drawn and centrifuged at 3000RPM for 8 minutes. The PRP will be manually aspirated. For participants in the control group, PRP inside the syringe will be not be injected into the AITFL. Instead, the 25 guage needle will be passed 5 times into and adjacent to the defect of the AITFL seen on ultrasound.
All ultrasound-guided dry needling procedures will be performed by radiologist Dr James Linklater (JL) at Castlereagh Imaging St Leonards, Sydney.
After the intervention, participants will be given oral analgesia, and record a one week pain score and this will have the primary investigators contact details should there be any concerns.
Control group
Active

Outcomes
Primary outcome [1] 297281 0
Time to return to play (in days) will be assessed by direct self-reporting from participants on weekly review. It will be expected by the treating physician who will be monitoring weekly progress and clarified by contact with the team physiotherapist.
Timepoint [1] 297281 0
Time to return to play will be measured from the date of injury to the date of return to match-play within the Sydney Rugby Union Championship (of any duration).
Secondary outcome [1] 320577 0
Ankle range of motion, specifically the toe-to-wall dorsiflexion test in centimetres, normalised to foot length.
Timepoint [1] 320577 0
2 weeks following removal of CAM-boot during rehabilitation.
Within 1 week of return to play.
Secondary outcome [2] 320578 0
Balance will be assessed using the Star Excursion Balance Test, in 3 directions, normalised to leg length.
Timepoint [2] 320578 0
2 weeks following removal of CAM-boot during rehabilitation.
Within 1 week of return to play.
Secondary outcome [3] 320641 0
Pain scores (on a Visual Analogue Scale of 0-100) will be assessed prior to and following each testing occasion at rest. They will also be recorded before and after each functional test outcome measure in order to ensure undue pain is not caused by assessment.
Timepoint [3] 320641 0
2 weeks following removal of CAM-boot during rehabilitation. 3 attempts will be allowed and the participants will be asked not to jump if a small trial jump is painful or concerns them.
Within 1 week of return to play.
Secondary outcome [4] 320642 0
Vertical Jump height will be measured using a vertical jump mat test.
Timepoint [4] 320642 0
2 weeks following removal of CAM-boot during rehabilitation.
Within 1 week of return to play.
Secondary outcome [5] 320643 0
Agility will be measured using the Illinois Agility Test, with participants wearing preferred shoes on a hard, flat surface.
Timepoint [5] 320643 0
Within 1 week of return to play.
Secondary outcome [6] 320644 0
Ankle power will be assessed using a Triple Hop Test.
Timepoint [6] 320644 0
Within 1 week of return to play.
Secondary outcome [7] 320645 0
Fear avoidance beliefs (specific for rugby union) will be assessed at both testing occasions using the FABQ (Fear Avoidance Beliefs Questionnaire).
Timepoint [7] 320645 0
2 weeks following removal of CAM-boot during rehabilitation.
Within 1 week of return to play.

Eligibility
Key inclusion criteria
Any suspicion of ankle syndesmosis injury
Minimum age
16 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
A low probability of ASI (Ankle Syndesmosis Injury), previous ASI, previous ipsilateral fracture or surgery, concurrent injury likely to cause more prolonged disability, ankle fracture, frank tibiofibular diastasis on plain radiographs, osteochondral defect requiring surgery, concurrent acute grade 3 anterior talofibular ligament injury, and greater than 4mm tibiofibular separation on MRI.

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)
Centralised randomisation using NHMRC/Sydney University system. Telephone call from unblinded radiologist performing injections/dry needling prolotherapy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted-block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power calculations are based on published data (available at http://bmjopensem.bmj.com/content/1/1/e000033.full.pdf+html).
Sample size was calculated for a two-tailed comparison of an experimental group to a control group with a significance (alpha) of 0.05 and a power (1- beta) of 0.80. This was calculated using an inference of means method (mu1= 48 days, mu2= 69 days and common standard deviation sigma= 20 days). Under these assumptions, we calculate that we will need 15 subjects per group to complete the study. Assuming a 20% allowance for attrition, we will enroll 18 subjects per group.
Analysis of data will be performed using IBM SPSS Statistics version 22. Descriptive statistics will be performed on all continuous variables including histogram frequencies to assess normality. Baseline characteristics including age, weight, height, and syndesmosis width on MRI will be analysed using t-tests to detect any significant differences between cohorts. Similarly, quantitative outcome measures of pain, function and time to return to play will be analysed to compare groups using t-tests of independent samples. Where data is not normally distributed, non-parametric tests will be used to detect differences between groups.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2016
Actual
Date of last participant enrolment
Anticipated
1/08/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 292843 0
Self funded/Unfunded
Name [1] 292843 0
David Samra
Country [1] 292843 0
Australia
Primary sponsor type
University
Name
Arthritis and Musculoskeletal Research Group, University of Sydney
Address
Faculty of Health Sciences
Arthritis and Musculoskeletal Research Group
C43S - S Block Cumberland Campus
75 East Street
Faculty of Health Sciences, Lidcombe
University of Sydney, NSW Australia 2141
Country
Australia
Secondary sponsor category [1] 291587 0
None
Name [1] 291587 0
Address [1] 291587 0
Country [1] 291587 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 294346 0
Sydney University HREC
Ethics committee address [1] 294346 0
Margaret Telfer K07
University of Sydney NSW 2006
Ethics committee country [1] 294346 0
Australia
Date submitted for ethics approval [1] 294346 0
21/02/2016
Approval date [1] 294346 0
Ethics approval number [1] 294346 0

Summary
Brief summary
As a low risk, readily available treatment, PRP injections are becoming an increasingly popular therapeutic adjunct offered by musculoskeletal clinicians. However, there is a clear need to scientifically assess the merits of this treatment option for athletes with ankle syndesmosis injury in order to establish recommendations for evidence-based practice.
We published a pilot study entitled- "Effectiveness of a single platelet-rich plasma injection to promote recovery in rugby players with ankle syndesmosis injury". Available at http://bmjopensem.bmj.com/content/1/1/e000033.full.pdf+html
We found a reduction in return to play by 20.7 days for the intervention (PRP) group, when compared to an historical control treated with the same rehabilitation protocol. The study supports the viability of an RCT to fully evaluate this treatment. We have calculated that a minumum of 30 participants would be required to detect a significant difference between groups in return to play, but would define a clinically significant difference as a minimum of one week.

We will conduct a prospective randomised controlled trial comparing single US-guided PRP injection to an active placebo prolotherapy. Assessors, investigators and participants will be blinded to their allocation and only the treating radiologist who will only interact with particpants to perform injections, will know allocations.

Prospective participants from Rugby union clubs within the Sydney Rugby Union Championship will be invited to enrol. On clinical assessment, only those with a low probability for ASI will not be referred for MRI. After MRI, those meeting enrolment criteria and consenting to participate will be randomly allocated to PRP or active placebo groups, and given usual injury management in accordance with our previously published milestone based rehabilitation protocol (Samra et al 2015).

A single injection by co-author JL will be provided within 14 days of injury. A central randomisation register will provide the allocation to JL only. The injection protocol will be identical between groups, except for lack of injection of the PRP in the active placebo group. 1-2mL of 2% lignocaine will be infiltrated to the skin and superficial tissues. Blood will be drawn and centrifuged at 3000RPM for 8 minutes. The PRP will be manually aspirated. 0.5-1mL of PRP will be injected with a 25 guage needle into the defect of the AITFL seen on ultrasound in the intervention group. The active placebo group will undergo the same process with the omission of injection of the PRP. Instead, a peppering technique of 5 passes into the AITFL will be performed. Participants will be given oral analgesia and post-injection care information and followup. No other injections of the ankle will be permitted during the rehabilitation of these athletes or within 1 week of return to play.

Return to play will be recorded in days from injury onset to first competitive match (of any duration) played since injury
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63350 0
Dr David Samra
Address 63350 0
St Vincent's Sportsmed
Suite 407
St Vincent’s Clinic
438 Victoria Street
Darlinghurst NSW 2010
Country 63350 0
Australia
Phone 63350 0
+61477275715
Fax 63350 0
+61285804899
Email 63350 0
[email protected]
Contact person for public queries
Name 63351 0
Dr David Samra
Address 63351 0
St Vincent's Sportsmed
Suite 407
St Vincent’s Clinic
438 Victoria Street
Darlinghurst NSW 2010
Country 63351 0
Australia
Phone 63351 0
+61477275715
Fax 63351 0
+61285804899
Email 63351 0
[email protected]
Contact person for scientific queries
Name 63352 0
Dr David Samra
Address 63352 0
St Vincent's Sportsmed
Suite 407
St Vincent’s Clinic
438 Victoria Street
Darlinghurst NSW 2010
Country 63352 0
Australia
Phone 63352 0
+61477275715
Fax 63352 0
Email 63352 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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