Injecting a ruptured Achilles tendon with a small sample of a person’s own plasma, without the red blood cells, has no functional or other benefit. Plasma rich in platelets and white blood cells for the acute injury was compared with placebo.
The NIHR-funded trial involved 230 adults with acute Achilles tendon rupture (the tendon which connects the calf muscles to the heel). All were attending UK hospitals within 12 days of injury. The trial found no difference in function at 24 weeks after the plasma injection or placebo injection.
While previous studies have suggested some benefit for autologous (the person’s own) plasma injection treatment, the quality of that evidence to date has been weak, although the treatment is considered safe.
This was a robust trial design, which provides us with more knowledge about a treatment which is increasingly popular for soft tissue injury, but for which there is a lack of good quality clinical evidence.
Why was this study needed?
Rupture of the Achilles tendon causes pain and inability to push the foot down, typically affecting the person’s ability to work, do sports and carry out normal activities while the tendon heals.
It’s thought that platelet-rich plasma treatment could boost tendon healing. This is where blood is taken from the patient and spun in a centrifuge to remove the red blood cells, creating a small volume of plasma that is rich in platelets, white blood cells and growth factors, which can be injected into the tendon.
This treatment is increasingly being used in sports and orthopaedic medicine.
We know that platelet-rich plasma positively affects cellular and physiological tendon healing under laboratory conditions, but the quality of evidence in real-world clinical settings is poor. There are differences in the way the plasma is produced and many studies so far have been small. Both randomised studies and case series exist.
This trial sought to use a common and relatively uniform injury, to test a standardised preparation of platelet-rich plasma in a larger trial.
What did this study do?
PATH-2 was a randomised, placebo-controlled trial that took place across 19 UK NHS hospitals between July 2015 and March 2018. A total of 230 adults with acute Achilles tendon rupture took part. The average age was 46 years, and 25% of participants were female.
Participants were randomised to receive an injection of either 4ml of platelet-rich plasma (114 people) or placebo using a ‘dry’ needle (116 people). Both groups received standard follow-up care, which included ankle immobilisation followed by physiotherapy.
At 24 weeks, they completed the heel rise endurance test. This involves standing on a 10% inclined board on one foot at a time and raising the heel as high and as many times as possible in time to a metronome.
This was a rigorously conducted trial, with patients and assessors unaware of which group they were in.
What did it find?
- No difference was found between the groups in muscle tendon function according to the heel rise endurance test. This was measured by the limb symmetry index which compares the endurance scores between limbs (0% no limb symmetry, 100% perfect limb symmetry). Those who had a plasma injection had a limb symmetry index of 34.7% versus 38.5% for the placebo (adjusted mean difference [aMD] –3.9%, 95% confidence interval [CI] –10.5% to 2.7%).
- There was no difference in maximum height achieved in the heel rise endurance test, with limb symmetry index scores 55% in each group.
- There were fewer heel rise repetitions in the plasma injection group, with a limb symmetry index score that may have arisen by chance: 50% in the plasma group compared with 61% for the placebo group.
- A similar number of adverse effects occurred in each group such as swelling or bruising of the lower leg and foot, technical complications of having a cast or foot splint and discomfort during rehabilitation.
- There was no evidence of any difference between the groups at shorter follow up — 4, 7, and 13 weeks — or in Achilles tendon rupture pain score, or pain during the two weeks after the injection.
What does current guidance say on this issue?
A NICE Clinical Knowledge Summary from 2016 advises that Achilles tendon rupture has a recovery period of 12 weeks.
NICE 2013 interventional procedure guidance on autologous blood injection for tendinopathy (IPG438) states that there are no safety concerns for this treatment, but limited clinical evidence of its effectiveness. NICE advises clinicians who want to use this treatment to ensure the patient is well informed, and to audit the treatment and outcome.
What are the implications?
Autologous platelet-rich plasma injections are administered within the NHS for some types of soft tissue injury; for example, tennis elbow. Although systematic reviews of available evidence have taken place, it has generally been difficult to compare outcomes of trials because of many differences in the way that this fast-growing treatment area is practised.
This was the largest trial to date on this treatment, and the researchers’ attempts to standardise and control it are credible, so the results do raise important doubts about the effect of the treatment. The findings will be of interest to orthopaedic clinicians.
Citation and Funding
Keene D, Alsousou J, Harrison P et al. Platelet rich plasma injection for acute Achilles tendon rupture: PATH-2 randomised, placebo controlled, superiority trial. BMJ, 2019;367:l6132.
This project was funded by the Efficacy and Mechanism Evaluation Programme, an NIHR and Medical Research Council (MRC) partnership (project number 12/206/30).
NICE. Autologous blood injection for tendinopathy. IPG438. London: National Institute for Health and Care Excellence; 2013.
NICE. Achilles tendinopathy. Scenario: management. Clinical Knowledge Summary. London: National Institute for Health and Care Excellence, updated January 2016.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre