Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture

Abstract

BackgroundAchilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies.Methods and designThis is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference.Participants will be followed up with blinded assessments of muscle–tendon function, quality of life, pain and overall patient’s functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations.Ethics and disseminationThe protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals.Trial registration numberISRCTN: 54992179, assigned 12 January 2015. ClinicalTrials.gov: NCT02302664, received 18 November 2014. UK Clinical Research Network Study Portfolio Database: ID 17850.

The use of platelets in regenerative medicine and proposal for a new classification system: guidance from the SSC of the ISTH

“…The statements presented here should contribute to improving the standardization and design of future clinical trials using platelets in regenerative medicine, and agree with some parts of recent recommendations . Future trials should not only be appropriately controlled and adequately powered, but also take into account the content and quality control of the platelet preparations to ensure that clear correlations between the products and outcomes are established . Further studies on the mechanism of platelet tissue regeneration and optimal platelet preparation may help to elucidate the best combination of bioactive factors to achieve maximal regenerative activity .…”

Platelet rich plasma injection for acute Achilles tendon rupture: PATH-2 randomised, placebo controlled, superiority trial

“…PATH-2 was a randomised, placebo controlled, multicentre, two arm, parallel group, superiority trial with masked participants and outcome assessors conducted at 19 hospitals in the United Kingdom. The trial methods, interventions, and analysis plan have been published 1516…”

“…The initial sample size target was 214, based on detecting a standardised difference of 0.5 at 24 weeks in the primary outcome (based on data from a previous trial where a clinically important difference of 10% with a standard deviation of 20% from the non-surgical group was observed at this time point post-rupture25). The sample size was increased on the data monitoring and ethics committees’ advice, based on a prespecified masked review of the original sample size assumptions (primary outcome standard deviation) 1516. An initial review on the overall patient population (not separated by treatment arm) was undertaken after the first 27 participants reached 24 week follow-up, at which time the standard deviation was lower than assumed.…”

Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

“…The protocol 73 was designed following a small-scale pilot study with the help of Achilles tendon injury patients at the John Radcliffe Hospital and the Oxford Trauma User Group (OTUG), which is composed of patients who have experienced the John Radcliffe Hospital orthopaedic trauma service and who volunteer to engage on clinical and research issues. Recommendations of OTUG members were incorporated in the original research proposal.…”