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

Abstract

Background Achilles tendon rupture (ATR) has a long healing period, which is challenging for patients and clinicians. Platelet-rich plasma (PRP) is an autologous concentration of platelets thought to improve tendon function recovery. Although preliminary research has indicated positive effects, there is, as yet, no evidence of clinical efficacy from adequately powered robust clinical trials. Objectives The objectives were to determine the clinical efficacy of PRP in patients with acute ATR using an objective mechanical muscle–tendon function measure and patient-reported outcome measures (PROMs), and to determine which PRP components contribute to its mechanism. Design This was a multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial (RCT) comparing PRP with placebo. Two embedded substudies investigated the PRP’s quality and composition and its effects on healing tendon tissues. Setting This trial was set in trauma and orthopaedic surgery departments in 19 NHS hospitals in England and Wales. Participants Adults with acute ATR presenting within 12 days of injury to be treated non-surgically were eligible. Patients with platelet dysfunction or leg functional deficiency were excluded. Interventions Participants were randomised 1 : 1 to the PRP injection group or the placebo group (dry needle in the rupture gap) by central computer-based randomisation using minimisation, stratified by centre and age. Main outcome measures The primary outcome measure was the Limb Symmetry Index (LSI) of work during the heel-rise endurance test at 24 weeks. Secondary outcomes measures, collected at 4, 7, 13 and 24 weeks, were repetitions, maximum heel-rise height, Achilles tendon Total Rupture Score (ATRS), quality of life (as measured using the Short Form questionnaire-12 items version 2), pain and participant goal attainment. Needle biopsies of the affected tendon zone were taken under ultrasound guidance at 6 weeks from 16 participants from one centre. Whole blood was analysed for cell count. PRP was analysed for cell count, platelet activation and growth factor concentration. The primary analysis was intention to treat. Results A total of 230 participants were randomised: 114 to the PRP group (103 treated) and 116 to the placebo group (all treated). One participant withdrew after randomisation but before the intervention. At 24 weeks, 201 out of 230 participants (87.4%) completed the primary outcome and 216 out of 230 participants (93.9%) completed the PROMs. The treatment groups had similar participant characteristics. At 24 weeks, there was no difference in work LSI (mean difference –3.872; 95% confidence interval –10.454 to 2.710; p = 0.231), ATRS, pain or goal attainment between PRP- and placebo-injected participants. There were no differences between the groups in any PROM at any time point or in complication rates, including re-rupture and deep-vein thrombosis. There was no correlation between work LSI and platelet activation in PRP, or erythrocyte, leucocyte or platelet counts in whole blood or PRP. Biopsies showed similar cellularity and vascularity between groups. Conclusions This trial design and standardised PRP preparation gives the first robust RCT evidence about PRP’s role in managing ATR, which suggests that PRP offers no patient benefit. Equally robust evidence to investigate PRP application in tendon and soft tissue injuries is required. The 24-month follow-up will be completed in April 2020. Trial registration Current Controlled Trials ISRCTN54992179. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The trial was supported by the NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship programme.

Achilles Tendon Rupture: Mechanisms of Injury, Principles of Rehabilitation and Return to Play

“…Trauma mechanisms that lead to an ATR are now well understood, classically occurring due to a single high-load impact or an acceleration–deceleration mechanism [ 1 , 29 ]. Degenerative changes are present in spontaneous tendon ruptures and may lead to a predisposition to ATR [ 29 , 37 , 38 ].…”

“…Degenerative changes are the most common histological findings in spontaneous tendon ruptures (such as high vascularity, collagen disorganization and hypercellularity relatively close to the ruptured site) and may lead to reduced tensile strength and a predisposition to rupture [ 29 , 37 , 38 ].…”

Characteristics of L-PRP preparations for treating Achilles tendon rupture within the PATH-2 study

“…116 were allocated to, and received, placebo. For full details of the trial primary and secondary outcomes refer to the main study paper and monograph [27,28]. Table 1 summarises all of the cell count and growth factor measurements within the L-PRP preparations in the PATH-2 trial.…”

A 10-year impact assessment of the Efficacy and Mechanism Evaluation (EME) programme: an independent mixed-method evaluation study

“…For example, one EME project showed that platelet-rich plasma, commonly used in the treatment of Achilles tendon rupture, offers no patient benefits compared with placebo. 47 With continuing growth in the market, 48 and a rapid increase of platelet-rich plasma application in sport injuries in Europe, 49 the finding will help inform clinical decision-makers and limit the cost burden of this treatment in managing Achilles tendon rupture. Box 7 provides another example of avoided cost to the health service.…”