Effect of a Platelet Rich Plasma (PRP) injection on the outcome of chronic lateral epicondylitis.
A double blinded randomized controlled clinical trial.

Tendinopathy is a common problem in the general population. It may result from
acute trauma, but more commonly from overuse. One of the most common
tendinopathies for the upper extremity is lateral epicondylitis . The incidence
of lateral epicondylitis in the general population is 0.54 percent, which
increases to 1.26 percent for the age group of 40 to 50 years and decreases
with older age.
Lateral epicondylitis is known to be a self limiting disease, since 80 % of the
patients with symptoms of a more than six weeks lasting lateral epicondylitis
are much improved or completely recovered within six months and 90% within one
year . In this study a six point Likert type scale was used for measuring the
improvement. Success rates were calculated from this scale by scoring *much
improved* en *completely recovered* as a success. When separating these two
outcomes a large difference is seen, with *completely recovered* being far less
than *much improved*.
Another study shows that only one third of the patients reports full recovery
at one year implicating that many patients keep complaints. Among the factors
that predict poor outcome are long duration of elbow complaints and severe pain
at presentation and probably history of elbow complaints, involvement of the
dominant side, female gender and older age.
For patients with chronic complaints, different treatment options have been
proposed. The injection with corticosteroids is still a treatment which is
frequently used. However, recent research shows although the short term results
are better, the long term results are worse compared to wait and see policy or
physiotherapy .
New therapies are being developed, because current therapies are not
satisfactory in patients with chronic complaints. One promising new therapy is
local injection with Platelet Rich Plasma (PRP). PRP can be derived from
centrifuging autologous whole blood. This procedure results in an 8-fold
increased platelet plasma concentration . In the *90s the PRP injection was
utilized for surgical wound healing. The platelets enhance tissue regeneration
and healing . Later on, PRP injections were also used in the treatment of
tendinopathies .

Several studies compared a PRP injection with another injection therapy.
Two studies compared the effectiveness of a PRP injection to the effectiveness
of autologous blood injection. Only after six weeks there was a statistically
significant difference in pain in favour of PRP, which disappeared in the long
term20. Both therapies are useful in patients who are resistant to
physiotherapy: approximately 70% improved in clinical outcomes. No
statistically significant difference was detected between the two therapies. In
the study of Creaney et al. the investigators gave 2 injections instead of one,
the second one a month after the first one. Furthermore one of the exclusion
criteria was having had an injection therapy in the past. The percentage
converted to a surgery was twice as high in the autologous blood group compared
to the PRP group (20%vs10%).
Wolf et al. found no difference in outcome as for function and pain when
injections with PRP, corticosteroids and saline, all with 1 ml lidocaine, were
compared . All injection types gave improvement of the tendinopathy. They only
included patients with complaints for less than 6 months, which makes it hard
to subscribe the improvement to the therapy rather than the natural healing
process. Furthermore the mixture of PRP with lidocaine can have a negative
influence on the tenocyte proliferation and cell viability of the PRP solution
.
Krogh et al. also compared a PRP injection, a glucocorticoid injection and a
saline injection . They found no significant pain reduction between the
different groups at 3 months, while glucocorticoids had a short term
pain-reducing effect at 1 month in contrast to the other therapies. They
originally planned the pain PRTEE score at 12 months as their primary endpoint,
however due to a high dropout number they decided to use the scores at three
months as primary endpoint.
Peerbooms et al. compared a PRP injection to an injection with corticosteroids
and found that initially the corticosteroid group did better, however after 8
weeks the PRP group did better up to 1 year . This effect was still visible
after 2 years . Because the known poorer outcome at 1 year of the
corticosteroid group compared to a wait and see policy, it is difficult to
subscribe the significant difference seen in this study to the positive effect
of PRP or the negative effect of the corticosteroids.
Kazemi et al compared an autologous blood injection with a corticosteroid
injection and saw that the blood injection was more effective in the short term
than the corticosteroid injection . This in contrast with the findings that
corticosteroids do better in the beginning.
Mishra and colleagues conducted two studies in which they compared an injection
with PRP with a injection with bupivacaine. The latest study was conducted with
225 patients. They found a statistically significant drop in painscore of 71.5%
after 24 weeks for the PRP group versus 56.1% for the bupivacaine group. No
statistically significant difference was found in the PRTEE score, they both
improved from baseline to 24 weeks (PRP 54.15-16.17 vs control 57.71 -21.06).
Some conclusions can be drawn from these studies. First of all, none of the
studies reported any severe adverse effects. Many studies had serious
methodological problems, including the duration of complaints shorter than 6
months, inhomogeneous patient populations, high rates of loss to follow up and
an active agent as control. Furthermore, the results do not favour PRP
unequivocally compared to other types of injection therapy. The effectiveness
of PRP treatment in patients suffering from chronic lateral epicondylitis is
still ambiguous. Therefore we study PRP treatment in a double blind randomized
controlled trial in a homogeneous patient population with respect to duration
of complaints (> 6 months) and insufficient recovery after a 5-weeks
multidisciplinary treatment. The following research question is addressed: does
a single PRP injection result in a clinical relevant reduction of the
complaints at six months, compared to an injection with saline.
By comparing the intervention group with a control group, which receives an
inert saline injection, we will be able to subscribe the results to the PRP
solution when there is a significant difference. And the patient can be spared
from an operation. When there will be no significant difference, this
relatively expensive therapy can be replaced by an alternative cheaper therapy.
A next interesting question will then be if the same results will be obtained
with dryneedling.

The effectiveness of PRP treatment in patients suffering from chronic lateral
epicondylitis is still ambiguous. Therefore we study PRP treatment in a double
blind randomized controlled trial in a homogeny patient population with respect
to duration of complaints (> 6 months) and insufficient recovery after a
5-weeks multidisciplinary treatment. The following research question is
addressed: does a single PRP injection result in a clinical relevant reduction
of the complaints at six months, compared to an injection with saline.

All outpatients presented to the departments of orthopaedic surgery and
rehabilitation medicine with chronic lateral epicondylitis are first offered a
rehabilitation program of five weeks, in which they execute a home-based
fitness program supported by two visits to the occupational therapist and three
visits to the physiotherapist. If necessary, the patients receive a cock-up
splint, which they wear during physical activities. Only patients who do not
respond sufficiently to the rehabilitation program (PRTEE score *40) and who do
meet the inclusion criteria are eligible for this double blinded randomized
controlled trial. Since there exists no golden standard therapy, neither
evidence based or consensus based, a inert salinw injection was chosen as the
optimal control therapy. Patients are only included if they sign the informed
consent, implicating that the randomization can proceed.
Participants will be randomly allocated to the experimental group or the
control group. The duration of the study will be 6 months from the moment of
injection. All visits will be at the department of rehabilitation of hospital
Gelderse Vallei and the participants will be guided during these visits by a
physical therapist. The participants who were allocated in the control group
will have the opportunity to receive a PRP injection after six months.

27 ml of whole blood will be taken from the cubital vein of each patient, three
ml of citrate will be added to prevent the blood from clotting. If the patient
is randomized to the PRP injection group, the collected blood is centrifuged
for 15 minutes at 3200 RPM. The platelet poor plasma is discarded and two ml of
PRP will be aspired, after re-suspending the platelets the remaining PRP will
be aspired. To match the pH of the tissue in which the PRP is injected, 0.05 ml
8.4 % sodium bicarbonate per ml platelet concentrate is added (GPS III, Biomet,
Warsaw Indiana, USA). If the patient is randomized to the control group, the
blood will be discarded. The patient will be blindfolded to garante that the
patient does not know in which group he is allocated. The radiologist documents
the laesion seen on ultrasound, to compare with the ultra sound made after 6
months. The radiologist performs the injection under ultrasound guidance and is
not further involved in the follow up.

Risks of the injection:
Possible complications: Bleeding, infection, nerve damage, pain and stifness
after injection.

Burden:
Venous blood withdrawal and injection in tendon extensor loge of the elbow (90
minutes).
3 visits at 1, 3 and 6 months. During these visits, which will take 30 minutes
of their time, the participant fills in a questionnaire and gripstrength will
be measured. At six months an ultrasound will be made, which takes another 30
minutes.
Furthermore some do's and dont's around injection time and before the visits to
our hospital. They have to perform their exercises, they are'nyt aloud to take
NSAID before and after the injection and they can't take a painkiller the two
days prior to the visit to our hospital.