Horizon Scanning Centre
September 2012
WOUNDCHEK™ Protease Status
point of care test for chronic
wounds
SUMMARY
Lay
summary
click here
This briefing is
based on
information
available at the time
of research and a
limited literature
search. It is not
intended to be a
definitive statement
on the safety,
efficacy or
effectiveness of the
health technology
covered and should
not be used for
commercial
purposes or
commissioning
without additional
information.
The WOUNDCHEK™ Protease Status test is a new
point of care (POC) test designed to assess
protease (or enzyme) activity levels in chronic (longlasting) wounds. A chronic wound typically shows
no sign of healing over four to six weeks. High
levels of proteases (found in wound fluid) are
associated with poor wound healing. This POC test
can indicate within 15 minutes whether protease
activity levels are elevated. This may help clinicians
to make quicker, better informed and cost-effective
decisions about which treatment to use. However,
more trial evidence is needed before it is known
what the true clinical benefits of adding this new test
might be.
© Systagenix
BACKGROUND
Chronic (long-lasting) wounds are also known as ulcers and can be found on
the leg, foot or pelvic region and are caused by a number of conditions
including diabetes. To be considered ‘chronic’ (or non-healing), a wound will
have no significant signs of healing over four to six weeks. A typical example
of a chronic wound is a venous leg ulcer, which develops when persistently
high blood pressure in the veins of the legs (venous hypertension) causes
damage to the skin, which eventually breaks down and forms an ulcer. One
expert comments that around 15% of patients with diabetes develop foot
ulcers and these can lead to amputation. Common symptoms of chronic
wounds include pain, itching and swelling in the affected area, and these
symptoms are frequently associated with poor sleep, loss of mobility and
social isolation. The impact on the patient’s quality of life can be significant.
In the UK, chronic wounds represent a very significant burden to patients and
the NHS with around 200,000 patients being affected1. The cost to the NHS
of caring for patients with a chronic wound is estimated at £2.3-3.1 billion per
year, and this treatment accounts for about 2-3% of the NHS budget1.
This briefing presents independent research funded by the National Institute
for Health Research (NIHR). The views expressed are those of the author
and not necessarily those of the NHS, the NIHR or the Department of Health.
NIHR Horizon Scanning Centre, University of Birmingham
Email: [email protected]
Web: www.hsc.nihr.ac.uk
NIHR Horizon Scanning Centre
Wound dressings alone account for about £120 million of prescribing costs in primary care in
England each year2.
Venous leg ulcers affect around 1 person in 500 in the UK. This rate rises significantly with
age, with an estimated 1 person in 50 over the age of 80 developing this condition3.
Chronic wounds have high levels of naturally occurring enzymes called proteases (e.g.
matrix metalloproteinases or MMPs and elastase) that are responsible for breaking down
and removing damaged tissue and low levels of growth factors that are important for healing.
All wounds require a certain level of proteases for healing, but high concentrations are
damaging as they prevent the growth of new healthy tissue. MMPs are found in all wounds,
but there is an imbalance in these substances in chronic wounds. Proteases are found in
exudate (wound fluid) and if a wound produces a large amount of this fluid the healing
process is likely to be slow4,5.
Experts agree that there is now a lot of evidence that high or elevated protease activity
(EPA) is the best available biochemical marker for predicting poor healing of wounds5,6. A
recent study showed that chronic wounds with EPA have a 90% probability of not healing
without appropriate treatment7.
CURRENT PRACTICE
Currently EPA in chronic wounds is often undetected as there are no obvious visual signs
and laboratory testing of wound biopsies for protease activity is not part of routine practice
and has only been carried out for research purposes8.
In wounds that are not healing as expected, EPA may be suspected in a wound that has not
responded to treatment or that has stalled after initially successful treatment. Clinical signs of
inflammation, which may indicate high protease activity, may be difficult to distinguish from
signs of infection5.
To date, research studies have analysed types, levels and activities of proteases in wound
fluid from wound biopsies. Analysis involves several different techniques such as ELISAs
(enzyme-linked immunosorbent assay) that use antibodies to measure levels of proteases
and assays that measure the enzymatic activity of proteases5. These laboratory assays are
not undertaken outside of research settings and will take at least 24 hours to obtain the
results.
The treatment pathway for chronic wounds can be complex due to the underlying condition
causing the wound and the different phases of healing. However, treatment usually includes
wound assessments and cleaning (using non-toxic and non-irritating solutions), debridement
(a procedure to remove non-viable or dead tissue) and dressing. Wound assessments can
be carried out by specialist tissue viability nurses.
There are a number of treatments that may reduce protease activity in wounds and
encourage healing including5,9,10:
• Protease modulating dressings which claim they can reduce protease activity (e.g.
MMPs), although evidence is limited.
• Specialist dressings and devices that absorb and remove exudate (protease-containing
fluid). Specialist dressings are more expensive (could be up to twice the cost) than
standard dressings and are not always used appropriately. Dressings are typically
replaced every other day or even a couple of times each day if the wound is wet.
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NIHR Horizon Scanning Centre
• Medicines to stop protease activity e.g. oral or topical doxycycline, an anti-inflammatory
and antimicrobial, although there is limited evidence of how well they work.
NEW TECHNOLOGY
Systagenix has developed the WOUNDCHEK™ Protease Status test in collaboration with
Alere. The test uses a sample of wound fluid and can indicate within 15 minutes whether
protease activity levels in wounds are elevated. The test is designed to form part of routine
wound assessments and can identify those wounds that are not healing due to the presence
of EPA and therefore may need protease modulating therapy. The test is point of care,
meaning it is intended to be performed in GP surgeries, community clinics or in the patient’s
home and the sample does not need to be sent to a laboratory.
The test is a disposable self contained kit that includes a test card, sterile wound swabs,
reagent and a result interpretation strip. The wound fluid sample is collected by swabbing
the surface of the wound. The reagent is added to the test card, then the swab is placed
inside the test card and the test result appears in a window and can be visually interpreted
using a reference strip that is provided.
The WOUNDCHEK™ Protease Status test was CE marked and launched in the UK in
January 2012. The cost of each test kit (includes 12 individual tests) is approximately
£21.50.
CLINICAL STUDIES AND RESEARCH QUESTIONS
There are currently no published clinical trials demonstrating the clinical efficacy of
WOUNDCHEK™ Protease Status in guiding patient care.
There are two registered ongoing and unpublished non-comparative studies of
WOUNDCHEK™ Protease Status test that started in March 2012, the estimated completion
date for both being March 2013. The estimated enrollment is 250 patients for each study.
The studies aim to determine if wounds with EPA treated with targeted interventions, such
as protease modulating therapies, can improve clinical outcomes of patients with venous leg
ulcers11 and with diabetic foot ulcers12. All patients are tested using WOUNDCHEK™
Protease Status. The primary endpoint for both studies is to identify EPA wounds using
WOUNDCHEK™ Protease Status and to assess the healing outcomes (wound healing
trajectory by week 4, indicative of potential to heal by week 12) of two treatments (including
a protease modulating therapy).
Randomised controlled trials where treatment is guided with or without WOUNDCHEK™
Protease Status are needed as this would provide the strongest evidence as to whether
adding this test to routine practice would bring clinical benefits.
POTENTIAL IMPACT
Chronic wounds represent a very significant burden to patients and the NHS in the UK. This
burden is likely to increase over time as the overall population increases in age and the
prevalence of conditions such as obesity and diabetes rises.
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NIHR Horizon Scanning Centre
A point of care test to measure protease levels may help clinicians to make informed and
cost-effective decisions about which treatment to use next. For example, it would not be
appropriate to use the more expensive protease modulating dressing on a wound without
elevated protease activity. If the WOUNDCHEK™ Protease Status test proves effective it
could lead to faster wound healing and advantages such as avoidance of delays in
treatment, avoidance of unnecessary treatments, less nursing time, fewer clinic visits for the
patient and shorter overall treatment duration. The test may also help to avoid the use of
expensive diagnostic tests, such as invasive wound biopsy, although this is rarely done.
However, for a point of care protease status test to become integral to UK practice, trial
evidence will be required to demonstrate that identifying the protease status and then
adapting treatment to take account of this status, will improve health and save resources.
Lay summary
The WOUNDCHEK™ Protease Status test is a new test designed to help doctors and
nurses decide how best to treat long-lasting wounds like leg ulcers. The test looks for
raised levels of enzymes called proteases which we know goes along with poor healing.
The test may help doctors make quicker decisions about which treatment to use and
this may lead to faster wound healing for the patient. But more studies are needed
before we know how well it works and how well this test helps doctors make decisions.
REFERENCES
1
Posnett J and Franks PJ. The burden of chronic wounds in the UK. Nursing Times 2008; 104: 3:
44–45. www.nursingtimes.net/nursing-practice/clinical-specialisms/wound-care/the-burden-ofchronic-wounds-in-the-uk/527138.article
2
National Prescribing Centre. Evidence-based prescribing of advanced wound dressings for
chronic wounds in primary care. MeReC Bulletin 2010; Vol. 21: No. 1.
3
NHS Choices. Leg ulcer, venous. http://www.nhs.uk/Conditions/Leg-ulcervenous/Pages/Introduction.aspx Accessed 8 August 2012.
4
Trengove NJ, Stacey MC, MacAuley S et al. Analysis of the acute and chronic wound
environments: the role of proteases and their inhibitors. Wound Repair and Regeneration 1999;
7(6): 442-52.
International consensus. The role of proteases in wound diagnostics. An expert working group
review. London: Wounds International 2011. www.woundsinternational.com. Accessed 2 August
2012.
5
6
World Union of Wound Healing Societies. Principles of best practice: A consensus document:
MEP Ltd. London. 2008.
7
Serena T, Cullen B and Bayliff S. A survey: the importance of proteases in wound healing and
wound assessment. Poster, Wounds UK 2011.
8
Snyder R, Serena T and Cullen B. A survey: the importance of proteases in would healing and
wound assessment. Poster, Wounds UK 2011.
9
NHS West Midlands. Chronic Wounds Toolkit. 2010.
www.westmidlands.nhs.uk/LinkClick.aspx?fileticket...tabid=631 Accessed 11 July 2012.
10 Werdin F, Tennenhaus M, Schaller HE et al. Evidence-based Management Strategies for
Treatment of Chronic Wounds. Eplasty 2009; 9: e19. Published online 2009 June 4.
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11 ClinicalTrials.gov. WOUNDCHEK™ Protease Status point of care (POC) diagnostic test on VLU
http://clinicaltrials .gov/ct2/show/NCT01537003 Accessed 8 August 2012.
12 ClinicalTrials.gov. WOUNDCHEK™ Protease Status point of care (POC) diagnostic test on DFU
http://clinicaltrials. gov/ct2/show/NCT01537016?term=woundchek&rank=2 Accessed 8 August
2012.
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