Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02302664 |
| Other study ID # |
14/SC/1333 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2015 |
| Est. completion date |
March 8, 2018 |
Study information
| Verified date |
June 2017 |
| Source |
University of Oxford |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Platelet Rich Plasma in Achilles Tendon Healing
Does using a Platelet Rich Plasma (PRP) injection immediately before standard casting benefit
patients aged 18 or over who are suitable for nonsurgical treatment of the Achilles tendon
rupture (ATR)? This is a multicentre, blinded, randomised, placebo controlled trial with two
sub studies: (1) blood sample analysis and (2) needle biopsy in 16 participants.
ATR is the most common tendon injury and leads to months of incapacity. With an average work
absence of 63108 days there are significant societal and National Health Service (NHS) costs.
PRP potential benefit is to improve recovery and return to normal activities earlier, and
reduce the NHS and societal impact. The investigators will investigate the efficacy of PRP
using disease specific and patient important outcomes to improve the evidence for this
treatment of ATR.
A minimum of 15 United Kingdom (UK) NHS hospitals will be included to recruit 214
participants. Patients will be identified in the orthopaedic outpatient clinic, usually
following an emergency hospital attendance for ATR. After checking eligibility and the
informed consent process, baseline data is collected and participants randomised to either
'PRP injection' or 'Imitation (placebo) injection'. A participant's own blood sample is taken
and prepared according to allocation. The injection is delivered by a trained surgeon in
clinic who will be aware of allocation while the participant remains blind.
Participants complete a pain diary and have four study assessments at 4,7,13 and 24 weeks,
carried out by a member of the research team blind to allocation. Assessments take place over
the telephone or during a hospital outpatient visit. The 24 week hospital visit includes an
exercise test of ankle function. All assessments include collection of patient reported
responses to pre-set questions.
The results may be applicable to the many other tendon and ligament injuries. The National
Institute for Health Research (NIHR)/Medical Research Council (MRC) Efficacy and Mechanism
Evaluation Programme provides funding and University of Oxford is Sponsor.
Description:
PURPOSE The aim of this study is to evaluate the effectiveness of treating ruptured Achilles
tendon with autologous platelet rich plasma. The investigators plan to compare the outcome of
traditional methods of immobilisation in a cast with the outcome of the same methods after
applying platelet rich plasma to the ruptured tendon.
Spontaneous rupture of the Achilles tendon is the most common tendon injury in the human
body, it accounts for approximately 20% of all major tendon ruptures. Since the 1950s, the
incidence of Achilles tendon rupture has been increasing. The peak incidence of ATR is
between 30 and 40 years of age. Current treatments are associated with a significant risk of
rerupture for the Achilles tendonÍž this is up to 15%. Therapies are currently dominated by
the conflicting priorities of rapid rehabilitation and a return to work versus the risk of
rerupture and/or surgery. New cost effective treatments that reduce both the risk of
rerupture and time to functional healing are needed to address this challenge.
Platelets are blood cells that form blood clots in the injured tissues. Platelets have
evolved over millennia to deliver a combinatorial wound healing cocktail that comprises over
1100 active soluble and membrane bound components, delivered sequentially over a timeframe
from minutes to the lifespan of the platelets. Platelets and platelet derived growth factors
play important roles in the healthy response to injury, promoting healing of tissues, and
have been proposed as therapeutic agents. Their potential for tendon repair has been
demonstrated in laboratory experiments and animal models. One human investigation has been
published, a small study in athletes showing accelerated return to function with platelet
preparations from patients own blood after complete Achilles tendon rupture. However, there
has been no scientifically sound clinical research to assess the full potential of using
platelet preparations to accelerate healing of Achilles tendon.
Despite that lack of high quality trial data, PRP administration remains a potentially
attractive strategy to explore given it is of relatively low cost and minimally invasive.
There has been a recent steep growth in PRP use for musculoskeletal conditions. It is
estimated that PRP is used to treat 86,000 tendon disorders annually in the United States and
a similar number in Europe.
There is also evidence that PRP injections are being introduced in NHS clinical practice, in
addition to a wider use in private medicine within the United Kingdom. The investigators
surveyed the declarations of use of PRP in NHS hospitals and discovered four offering PRP for
tendon injuries. Without evidence of efficacy the consequences range from the NHS incurring
extra costs for a treatment with unproven clinical effects to the non deployment of an
effective autologous intervention. There is therefore a pressing need to undertake this study
before the use of PRP becomes widely adopted. The results of this study may inform the design
of a potential future clinical trial of optimal PRP therapy versus surgical repair for ATR in
restoring patient function.
The National Institute for Health and Care Excellence (NICE) review of PRP use (IPG 438)
states that specialist advisers noted that this was an established practice and it is of
concern that participants are being exposed to these intervention techniques without adequate
clinical investigation into their efficacy and validity. NICE encourages further research
comparing autologous blood injections (with or without techniques to produce PRP) against
established nonsurgical methods.
The proposed trial aims are:
1. Evaluate the clinical efficacy of PRP in acute ATR in terms of mechanical muscle tendon
function.
2. Evaluate the clinical efficacy of PRP in acute ATR in terms of patient reported
functional recovery, pain and quality of life.
3. Determine the key components of PRP that contribute to its mechanism of action.
4. Explore the immunohistochemical response of the healing tendon to PRP at the cellular
and tissue level.
STUDY DESIGN Platelet Rich Plasma in Achilles Tendon Healing (PATH-2) is a pragmatic
prospective multicentre, blinded, randomised, placebo controlled trial with two sub studies
embedded within the main study. The study aims to evaluate the clinical efficacy of PRP in
acute ATR in terms of mechanical muscle tendon function. To achieve the goals of this study
and produce high level evidence of PRP efficacy, the study is a randomised controlled trial.
The randomisation will reduce the risk of bias and the control arm will help to eliminate the
placebo effect. Patients and assessors are blinded to the applied treatment to reduce the
risk of bias.
The PATH-2 study will take place in a minimum of 15 NHS hospitals across the UK. Participants
will be identified in the orthopaedic/trauma outpatient clinic, usually following an
emergency hospital attendance for an Achilles tendon rupture. The investigators anticipate
the surgeon will confirm appropriateness for nonsurgical treatment and eligibility. A member
of the local research team will carry out the informed consent process, baseline data
collection and randomisation.
Participants will be randomised via a telephone or website randomisation service, and will be
allocated to receive either 'PRP injection' or 'Imitation (placebo) injection'. Treatment
will be administered by a surgeon during the outpatient visit. Those involved in treatment
delivery will be aware of treatment allocation due to the nature of the intervention.
Participants should remain blind to allocation throughout the study.
There are blinded outcome assessments at 4, 7, 13 and 24 weeks and 24 months after treatment.
For the first three (4, 7, 13 weeks) responses will be collected over the telephone or during
a hospital outpatient visit (where this coincides with local follow-up). The fourth follow-up
requires a hospital attendance at 24 weeks, with a face-to-face interview and assessment by a
physiotherapist/assessor. At this visit, the primary outcome (HRET) will be collected. The
final follow-up (24 months) is completed by post or telephone.
The two embedded sub studies are:
1. Sub study 1: Blood component (all participants, all sites) and PRP component analyses
(PRP intervention arm only). A blood sample will be taken from each participant after
consent and randomisation but prior to treatment. The samples will be analysed to
compare its composition by blood cell type. PRP samples will be prepared according to
treatment allocation and a portion will remain after treatment. This will be sent to a
central laboratory for later analysis (blood cells count, growth factors and platelets
viability).
2. Sub study 2: Immunohistochemistry analysis (16 participants from selected sites only who
have given consent to undergo the sample collection procedure). A needle biopsy of the
healing Achilles tendon under ultrasound guidance will be taking during an outpatient
visit. Samples will undergo immunohistochemistry analysis centrally in a specialist
laboratory.
