Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03479190 |
| Other study ID # |
IRAS 198415 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 3, 2018 |
| Est. completion date |
April 3, 2022 |
Study information
| Verified date |
March 2023 |
| Source |
Northumbria Healthcare NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Greater Trochanteric Pain Syndrome (GTPS), also known as Trochanteric Bursitis, is a painful
condition predominantly affecting middle aged women. It is characterised by pain in the
lateral hip exacerbated by movement and lying on the affected side. GTPS encompasses
different conditions including gluteus medius/minimus tendinopathy and bursal inflammation.
The treatment for this condition begins with conservative treatments of analgesia and
physiotherapy, which normally results in a resolution of symptoms. If this fails then steroid
injections have been shown to be effective. If this is not successful patients are offered
surgery. Steroid injections however may only be effective in the short term and sometimes
patients require repeat injections. Platelet rich plasma (PRP) is plasma taken from the blood
of the patient that has been treated so that it has a higher than usual concentration of
platelets in it. It has been postulated to promote healing in damaged or inflamed tissues.
Platelets contain a variety of growth factors, which are involved in healing. It has been
used in a variety of orthopaedic conditions such as lateral elbow epicondylitis, patellar
tendonitis, rotator cuff pathology and planter fasciitis. Studies have shown varying effects
of PRP in these conditions with most promise in plantar fasciitis and patellar tendonitis.
These conditions are similar to GTPS. A recent review of treatments for GTPS concluded that
more research into PRP efficacy in GTPS is required. We hypothesise that PRP is effective in
treating GTPS in patients who have not responded to conservative management (analgesia and
physiotherapy). This is an area that lacks research and could be valuable to those suffering
from GTPS. Further study is required as PRP could be used as instead of steroid injections or
if steroid treatments have failed and this could prevent patients from suffering further or
needing surgery.
The investigators propose a randomised control trial comparing a normal saline injection with
a PRP injection in patients with GTPS, diagnosed by MRI scan, who have not responded to
conservative treatments. Patients will receive either PRP or normal saline under ultrasound
guidance by a consultant rheumatologist. Sample size calculation has shown that the
investigators will need to recruit a total of 100 patients who will be randomised into either
arm (50 in each arm). The recruitment period will last 2 years with the whole trial aiming to
finish in 4 years from the proposed start date. Neither patients or the study team members
assessing the outcomes will know which treatment the patient received. Patients will be
followed up at 3, 6 and 12 months. The primary outcome measure will be a patient reported
outcome measure (PROM) i-HOT12 (international hip outcome tool) which is a valid and reliable
scoring system that assesses patient's ability to return to an active lifestyle through
obtaining subjective measures of symptoms, as well as determining emotional and social health
status.
This will be alongside secondary outcome measures Visual Analogue Pain Score, Modified Harris
Hip Score and EQ-5D collected. The proposal was discussed with a group of patients who
previously had treatment with Platelet Rich Plasma (PRP) injection for hip pain. A discussion
was had with regards the setup of a study and they were enthusiastic about this. A patient
information sheet was shown to them and modified as per their comments. Their advice was
obtained with regards the setup of this study, the randomisation into placebo arm, followup
frequency and the outcome measures. In particular, patients suggested that if placebo was not
working then a switch over to treatment arm should be discussed sooner than the initially
planned one year. This has been taken into account and six month has been agreed. The
proposal was also discussed in the NRES committee who are satisfied with the proposal.
Ethical approval has been granted and the study is registered with Health Research Authority
England.
Description:
1. What is the problem being addressed? Greater trochanteric pain syndrome (GTPS), also
known as trochanteric bursitis, is a painful condition characterised by pain around the
greater trochanter usually affecting middle aged women (1). It was first described, as
trochanteric bursitis in 1958 (2). Further details on the clinical symptoms published in
1978 as pain over the greater trochanter on walking, squatting or climbing stairs and
pain on lying on the affected side or when crossing one's legs (3). Little described
tenderness over the greater trochanter over the insertion of the gluteus tendons. GTPS
was a term used by Karpinski et al 1985 instead of trochanteric bursitis as patients did
not exhibit typical bursitis signs of swelling, heat, crepitus or fluctuation (4). This
notion has been supported by other studies (5) including a study performed by Bird et al
2001 evaluated 24 patients using MRI with the clinical picture of GTPS and found that
majority of them had gluteus medius tendon pathology with only 2 patients with
trochanteric bursal inflammation (1). Hence, GTPS instead of trochanteric bursitis
appears to be the more accurate way of described the clinical condition which seems to
have multiple facets in its pathology.
2. Why is the research important? Greater trochanteric pain syndrome (GTPS) is one of the
most common causes of lateral hip pain in adults and can be a painful and debilitating
condition which as a last resort requires surgery especially if it does not respond to
conservative treatments. The best estimates of prevalence are from a large,
community-based study with over 3000 adults aged 50 to 70 years, in which unilateral
GTPS was present in 15 percent of women and 6.6 percent of men. Bilateral GTPS was
reported in 8.5 and 1.9 percent of women and men, respectively. The usual age at
presentation is over 50 years, and the female to male ratio is approximately 4:1. It can
be associated with low back pain in 20-35%. Bilateral GTPS in particular is associated
with higher 20-meter walk time and chair stand time. It can lead to substantial
limitation of activity and poor quality of life. It is therefore important to look at
appropriate treatment options that will lead to quicker and more long-lasting recovery.
Currently the treatment ladder for GTPS consists of conservative measures such as
physiotherapy and NSAIDs. The majority of patients will settle with conservative
management however if this fails then more invasive treatment options include shockwave
therapy and corticosteroid injections. These second line treatments are important in
preventing the need for surgery as a last resort. (6, 7, 8). Corticosteroid injection is
an established second line treatment for GTPS that has been shown to be efficacious but
not necessarily long term as reported by a randomised study comparing steroid . (9) This
notion has been supported by numerous reviews of GTPS management (10, 11, 12, 13). It is
therefore imperative to explore treatment options that have the potential for
long-lasting benefits, in the form of regenerative medicine are explored. One such is
the use of platelet rich plasma (PRP) which will allow regeneration of cells and more
robust healing.
PRP is an autologous blood product which has been postulated to promote healing in
damaged or inflamed tissues including muscles, ligaments, bones and tendons. Platelets
contain a variety of elements including growth factors and cytokines which are involved
in tissue healing. These include platelet derived endothelial growth factor, platelet
derived growth factor, transforming growth factor, insulin like growth factor, vascular
endothelial growth factor, basic fibroblast growth factor. These growth factors are
present in the processes of tissue injury, inflammation and repair. Therefore the theory
is the higher the concentration of platelets, the more growth factors there will be
present to promote the healing process when administered directly to the area of
interest (14). PRP has been applied in other fields of medicine including regenerative
therapies in oral and maxillofacial surgery. (15, 16) Over the past decade or so there
have been numerous studies of PRP's efficacy in treating inflammatory musculoskeletal
conditions similar in pathology to GTPS, such as lateral epicondylitis, patellar
tendinitis, rotator cuff pathology, achilles tendonitis and plantar fasciitis. This has
been collectively reviewed by several authors with reports of mixed efficacy compared to
standard treatments for these conditions with the most promise shown in plantar
fasciitis and patellar tendinitis (17, 18). These reviews all report a lack of evidence
to fully support or reject PRP's efficacy in these conditions, except for achilles
tendonitis where PRP showed no difference compared with placebo in a randomised study
(19, 20). PRP's healing or regenerative properties have shown promise in other areas of
orthopaedics such as cartilage pathology (14).
The success of novel regenerative therapy in the form of PRP in a scientifically
conducted clinical study will be a major advance in our current knowledge base and will
have wider implications for its use in other fields of orthopaedics and will provide
better understanding in developing strategies for dealing with similar issues probably
even for degenerative conditions.
3. How does the existing literature support this proposal We have completed a systematic
literature review which has been submitted for publication. We used NICE healthcare
database advanced search (HDAS) via Athens (PubMed, MEDLINE, CINAHL, EMBASE and AMED
databases) to conduct our search from their year of inception to October 2017. In total,
four studies were included for analysis consisting of two randomised control trials and
two case series. We also identified four additional studies from published conference
abstracts (one randomised control trial and three case series). 209 patients included in
these studies with a mean age ranging from 48 to 76.2 years. Majority were females with
three months minimum duration of symptoms. Diagnosis was made using ultrasound or MRI.
Included studies used a variety of outcome measures. Improvement was observed during the
first 3 months after injection. Significant improvement was also noted when patients
were followed up till 12 months post treatment. We found that there is a paucity of
evidence reporting the efficacy of PRP in treatment of GTPS. The current literature has
revealed that PRP injections are relatively safe and can be effective. Considering the
limitations in these studies, we think more large-sample and high-quality randomised
clinical trials are required in the future to provide evidence of the efficacy for PRP
as a treatment in GTPS.
4. What is the research question / aims and objectives?
The aim of the trial is to investigate the clinical efficacy of the novel treatment
platelet rich plasma (PRP) in treating patients with GTPS. PRP's clinical efficacy will
be compared against a placebo injection of normal saline.
Hypothesis: PRP is an effective treatment for greater trochanteric pain syndrome.
5. Project Plan
Population: Patients with GTPS Intervention: Platelet rich plasma (PRP) injection into
trochanteric area under ultrasound guidance Comparator - Placebo of normal saline Outcome:
Validated patient reported outcome measures (iHOT-12), Visual Analogue Score for pain (VAS),
Modified Harris Hip Score (mHHS) and quality of life outcome (EQ-5D 3L) will be collected at
baseline, 3, 6 and 12 months will be compared within and between the PRP and normal saline
arms.
Design: The trial will be a two arm single centre double blind randomised control trial. The
study will include a two-way comparison between PRP and placebo normal saline injections for
treating GTPS. Participants will be reviewed at baseline, 3, 6 and 12 with patient reported
outcome measures (PROM) completed at each of these reviews.
Setting: Hospital outpatient Target population: Participants with GTPS will be identified and
referred for inclusion in the study by their main care provider (GP, Orthopaedic surgeon,
Rheumatologist).
Health technology being assessed: Platelet rich plasma injection (PRP)
Objectives of the Trial :
1. To test the hypothesis that PRP is effective in treating GTPS in patients who have
failed conservative management
2. To assess the duration of effect of PRP Outcome Measures Primary: The International Hip
Outcome Tool - 12 (iHOT-12) PROM scores Secondary: The Visual Analogue Score for pain
(VAS), Modified Harris Hip Score (mHHS) and the EQ-5D 3L scores
Power and sample size:
The primary outcome of interest is the change from baseline to 12 month follow-up for the
12-item International Hip Outcome Tool (iHOT-12). Statistical significance is set at 5% and
desired power at 90%, with two tailed tests applied. The minimally clinically important
difference (MCID) for the iHOT-12 has been reported as 10 (from 100) and the standard
deviation for the change in score from baseline as no greater than 21 by Sansone et al (23).
We conservatively assume that change in iHOT score from baseline in the steroid group will be
no more than 10 and the change in the iHOT score form baseline in the PRP group will be no
less than 27. Using these figures, a minimal sample size at follow up of 66 (33 in each
group) will be required. Pilot data obtained by our team suggest that the refusal to
participate rate should be no more than 25% and the dropout rate no more than 35% over 12
months. Refusal rates tend to be low in this patient group given the chronic nature of the
condition and the fact that patients will only be approached once conservative management has
failed. Thus, we will need to approach 135.4 (round up to 136) patients, and recruit 102
patients to achieve our target sample size.
Difference between current and planned care pathway: None
Dissemination Plan:
To ensure that the outputs from the research informs policy and practice and thereby
maximises the benefit to patients and the NHS, the following dissemination strategy has been
developed using evidence for translating knowledge into practice. From research evidence we
know that research is most effectively disseminated using multiple vehicles, ideally with
face to face interaction. So, in addition to giving written feedback to study participants,
dissemination activities will include development of links with key organisations such as
NICE, NHS Information Centre, NHS Commissioning Board and Quality Observatories to contribute
to and capitalise on their networks. In addition, media and national and international
medical conferences. Furthermore, Publications including Full, Executive Summary and Plain
English summary reports of the research, peer review journals and local NHS newsletters and
A5 laminate.
