Oct 5, 2016 - The potential innovative aspect is that UrgoStart uses a technology lipido-colloid nano- ..... Open RCT ..
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UrgoStart for chronic wounds Medtech innovation briefing Published: 5 October 2016 nice.org.uk/guidance/mib82
Summary The technology described in this briefing is the UrgoStart wound dressing. It is used to treat chronic wounds such as diabetic foot ulcers, pressure ulcers or venous leg ulcers, as well as non-healing acute wounds. The potential inno innovativ vative e aspect is that UrgoStart uses a technology lipido-colloid nanooligosaccharide factor (TLC-NOSF), which is designed to inhibit protease activity, the presence of which may impair wound healing. The intended place in ther therap apyy would be as an alternative to other advanced wound dressings in people with chronic wounds. The key points from the e evidence vidence summarised in this briefing are from 2 randomised controlled trials (RCTs), 1 prospective case series and a poster presentation of a crosssectional study. One RCT (n=117 patients) compared UrgoStart with an alternative protease modulating dressing. The other RCT (n=187 patients) compared UrgoStart with an identical dressing but without the NOSF protease modulating component. Both RCTs reported greater reductions in relative wound area when using UrgoStart dressings. Key uncertainties around the evidence are that the available RCTs follow up patients for 8 and 12 weeks, which in most cases is not long enough to reach complete wound healing. No studies were carried out in community settings. The cost per Urgostart dressing varies from £2.95 to £15.54 depending on the size and type, and some of these require additional absorbent dressings, retaining bandages or tape. Other dressings range from £1.00 to £7.07 for a similar range of sizes, depending on the type. © NICE 2017. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-andconditions#notice-of-rights).
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UrgoStart for chronic wounds (MIB82)
NICE has also published a medtech innovation briefing on the WoundChek Protease Status test for detecting elevated protease status.
The technology UrgoStart (Urgo Medical) is indicated for the treatment of chronic wounds, such as leg ulcers, pressure ulcers or diabetic foot ulcers, as well as for non-healing acute wounds. The dressings contain a layer of open weave polyester mesh, impregnated with hydrocolloid polymers, within a petroleum jelly (Meaume et al. 2002). The manufacturer calls this technology lipido-colloid, or TLC. UrgoStart also contains nano-oligosaccharide factor (NOSF), which inhibits protease activity, specifically matrix metalloproteinases (MMPs) and stabilising growth factors. MMPs are a family of enzymes that, together with other proteases, have a key role in wound healing. During normal wound healing, their functions include breaking down extracellular proteins and activating growth factors (Lazaro et al. 2016). In some wounds, protease activity can become excessive, damaging the wound area and delaying healing (International Consensus 2011). A review by Lazaro et al. (2016) found that chronic wounds show higher levels of protease activity than acute wounds, and that there is correlation between high MMP levels in chronic wounds and delayed wound healing. Protease imbalance may be only one of many factors that contribute to delayed wound healing (Gibson et al. 2009). The manufacturer claims that UrgoStart dressings promote faster healing in leg ulcers, pressure ulcers and diabetic foot ulcers. They state that UrgoStart should be used for a minimum of 8 weeks, with dressing changes every 2 to 4 days, up to a maximum of 7 days. Treatment of any critical colonisation (a build-up of bacteria causing delayed wound healing) is recommended before dressing use. Although protease modulation is a key feature of the UrgoStart dressing, the instructions for use do not state a need to test the wound for elevated protease levels before using the dressing.
The innovation The innovative feature of the UrgoStart dressing is the NOSF component, which is intended to act as a protease inhibitor. The technology lipido-colloid (TLC) component of the dressing is intended to create a moist, protected wound healing environment and is claimed to promote growth of fibroblast cells.
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Current NHS pathway NICE has published guidelines on the prevention and management of foot problems in people with diabetes, pressure ulcers, and surgical site infections. Although these guidelines give important recommendations about wound care, they do not make recommendations on specific products. NICE advice on wound care products and advanced and antimicrobial dressings for chronic wounds states that dressing selection should be made after careful clinical assessment of the person's wound, their clinical condition, and their personal experience and preferences. The NICE advice also states that the least costly dressings that meet the required clinical performance characteristics should be used, as there is insufficient evidence to determine whether modern or advanced dressings (such as hydrocolloids, alginates and hydrofibre dressings) are more clinically effective than conventional dressings for treating wounds. Additionally, NICE advice states that there is currently no robust evidence supporting the use of antimicrobial dressings (such as silver, iodine or honey) over non-medicated dressings for treating chronic wounds. The Scottish Intercollegiate Guideline Network (SIGN) guideline on the management of venous leg ulcers recommends simple non-adherent dressings and compression therapy. NICE is aware of the following CE-marked devices that appear to fulfil a similar function as UrgoStart: Promogran and Promogran Prisma (Acelity).
Population, setting and intended user UrgoStart dressings are intended for use by a healthcare professional, and may be used in a community or hospital setting. They are applied by the same clinical staff that would usually choose, apply and change the patient's dressings. This would typically be a nurse, including district nurses and tissue viability nurses, but may also include other staff such as podiatrists. UrgoStart is intended for use on patients with chronic wounds or acute wounds that are not healing at the expected rate. Some patients are at higher risk of wounds that are slow to heal, including patients with diabetes, venous insufficiency, and restricted mobility.
Costs The cost of a wound dressing is only a small component of the total treatment cost for chronic wounds. The cost of nursing time for treating the wounds is the main cost associated with treatment. The total treatment cost will be governed by the frequency of dressing changes, total treatment length and any additional treatment needs. © NICE 2017. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-andconditions#notice-of-rights).
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De Device vice costs Some UrgoStart products must be used with additional dressings and may be used with additional compression bandaging as clinically needed. Table 1 lists the costs of some of the UrgoStart products. A range of UrgoStart dressings are available: UrgoStart Contact – TLC-NOSF mesh, additional absorbent dressing and tape or a retention bandage also needed. UrgoStart – TLC-NOSF mesh with foam absorbent backing, tape or a retention bandage also needed. UrgoStart border – TLC-NOSF mesh with foam absorbent backing and an adhesive border to stick to the skin around the wound. No retention bandage needed.
Table 1: Cost of UrgoStart dressings Description
Cost (NHS Supply Chain) Additional information
Contact layers: UrgoStart Contact £2.94 to £9.88
5 x 7 cm to 15 x 20 cm
Foam dressings: UrgoStart
£4.69 to £11.70
6 x 6 cm to 15 x 20 cm
Adhesive foam dressing: UrgoStart Border
£5.43 to £15.54
8 x 8 cm to 20 x 20 cm (sacrum)
Costs of standar standard d car caree Table 2 shows the prices for a selection of alternative dressings which are likely to be used in current practice. Promogran is claimed to be a protease modulating dressing. A wide range of dressings are available for the treatment of exuding chronic wounds, and this is reflected in the wide variation in cost.
Table 2: Cost of compar comparator ator dressings Description
Cost (NHS Supply Chain) Additional information
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Protease modulators Promogran
£5.80
28 x 28 cm
Promogran Prisma
£7.07
28 x 28 cm
UrgoTul contact
£3.20
10 x 10 cm
Aquacell foam dressing
£2.65
10 x 10 cm
UrgoTul Absorb
£2.78
10 x 10 cm
Kendall non-adhesive foam dressing £1.00
10 x 10 cm
Tegaderm hydrocolloid dressing
£2.33
10 x 10 cm
Hydrosorb hydrogel dressing
£1.51
10 x 10 cm
Other dressings
Resource consequences UrgoStart and other protease modulating dressings are already in use within the NHS, and can be prescribed or purchased via usual arrangements. Faster wound healing could result in patient benefits and cost savings. There are 3 published cost models of the adoption of UrgoStart; one of which, Taylor (2012), is from an NHS perspective. This study found a cost saving of £1,812 per patient over a 1 year period when using UrgoStart compared to a neutral foam dressing in patients with chronic wounds. All 3 studies found UrgoStart to be cost saving compared to a neutral foam dressing. Any potential cost savings would only be realised if the UrgoStart provides improved wound healing compared to standard care and therefore reduces the cost of clinical staff time.
Regulatory information UrgoStart products are all CE marked as class IIb devices. The CE marks for the different UrgoStart dressings were awarded between 2006 and 2014. A search of the Medicines and Healthcare Products Regulatory Agency website revealed that no manufacturer Field Safety Notices or Medical Device Alerts have been issued for this technology.
© NICE 2017. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-andconditions#notice-of-rights).
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UrgoStart for chronic wounds (MIB82)
Equality consider considerations ations NICE is committed to promoting equality, eliminating unlawful discrimination and fostering good relations between people with particular protected characteristics and others. In producing guidance and advice, NICE aims to comply fully with all legal obligations to: promote race and disability equality and equality of opportunity between men and women, eliminate unlawful discrimination on grounds of race, disability, age, sex, gender reassignment, marriage and civil partnership, pregnancy and maternity (including women post-delivery), sexual orientation, and religion or belief (these are protected characteristics under the Equality Act 2010). Older people, people with diabetes and those with restricted mobility are more likely to have chronic or non-healing wounds. Age and disability are protected characteristics under the 2010 Equality Act.
Clinical and technical e evidence vidence A literature search was done for this briefing in accordance with the published process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting
[email protected].
Published evidence Four studies investigating the effectiveness of UrgoStart dressings are summarised in table 3. These include 2 randomised controlled trials (RCTs; Meaume et al. 2012 and Schmutz et al. 2008); a prospective case series (Richard et al. 2012) and a poster presentation of a cross-sectional study (Munter 2009). In total 1,341 patients were included in the 4 studies. The 2 RCTs had follow-up periods of 8 weeks (Meaume et al. 2012) and 12 weeks (Schmutz et al. 2008). The primary outcome in the RCTs was wound area reduction. The 2 comparative studies showed favourable results for UrgoStart compared to either a foam dressing or an alternative protease dressing. Three additional studies (table 4) were identified that modelled the cost of the UrgoStart dressing. Two studies (Taylor 2012, Augustin et al. 2016) were based on clinical data from the RCT by Meaume et al. (2012). The study by Taylor (2012) was a Markov model from an NHS perspective, using UK costs. The Augustin et al. (2016) study was a decision tree model with cost data from the German healthcare system. A third study, Maunoury et al. (2012) was only available as an abstract. This was a Markov model, based on French healthcare systems, with no information in the abstract
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on the source of clinical data. All 3 models found the use of UrgoStart to be cost effective or cost saving in the patient population studied. Tables 3 and 4 summarise the clinical and economic evidence as well as its strengths and weaknesses.
Table 3: Summary of clinical e evidence vidence Study
Details of interv intervention ention [and compar comparator] ator]
Outcomes
Strengths and limitations
Meaume 2012.
UrgoStart (n=93).
Median wound area reduction (WAR) was significantly higher
Strengths:
with UrgoStart vs. control 187 patients UrgoTul group. Absolute WAR, healing with venous Absorb rate, and percentage of leg ulcers (control, wounds with >40% surface (VLUs). n=94). area reduction were also DoubleDebridement significant in favour of blinded RCT. and UrgoStart. Multicentre compression (number of were used as centres not required. detailed), hospital setting (inpatients and outpatients). France.
Randomised, double-blinded study. Data analysis and paper authorship were independent. Limitations: Short treatment time of 8 weeks, wound healing not reached. Study financially supported by manufacturer who acted as supervisor and had access to data.
Patients were followed for 8 weeks, with evaluations at 2 week intervals.
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Schmutz 2008.
UrgoStart (n=57).
Wound area relative reduction Strengths: (RR) was in favour of Randomised study, blind UrgoStart. 117 patients Promogran assessment of wound area. with VLUs. (control, A superiority test of UrgoStart Limitations: n=60). compared with Promogran was Open RCT Not fully blinded, multicentre with blinded Debridement concluded (p = 0.0059). study may introduce wound and inconsistencies in treatment assessment. compression practices. Method of Multicentre were used as randomisation not reported. required. (27 centres). Wounds not followed to Patients complete closure. One author France (22 followed for was employed by the hospital 12 weeks, manufacturer of UrgoStart. centres). with weekly UK (5 assessment specialised until week 4, wound and every healing 2 weeks centres). thereafter. Richard 2012.
UrgoStart, no comparator.
33 patients with type 1 or 2 diabetes and neuropathic foot ulceration. Prospective case series.
Patients followed for a maximum of 12 weeks, or until full wound closure.
At 12 weeks there was a mean wound reduction of 62.7 ± 49.9%). In 10/33 (30.3%) of patients the wound healed completely.
Strengths: Consecutive enrolment. Baseline data from subjects who withdrew due to serious adverse events was included in the final analysis. Limitations: Non-comparative, small number of patients, wounds were examined by multiple observers in each centre.
Multicentre (14 hospitals). France.
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UrgoStart for chronic wounds (MIB82)
Munter 2009. 1007 patients.
UrgoCell Start, no comparator.
Crosssectional study.
The majority of clinicians (number not reported) and patients rated the dressing as useful or comfortable, respectively. There was a median reduction of wound size of 75%.
Multi centre (483).
Strengths: Large numbers of patients. Wide variety of wound types. Limitations: Poster only, full details not available as full paper was in German. Single arm, no comparator data.
Germany.
Table 4 Summary of economic e evidence vidence Study
Details of Outcomes interv intervention ention [and compar comparator] ator]
Strengths and limitations
Augustin 2016.
UrgoStart vs. UrgoCell Contact (neutral foam dressing)
Strengths:
Economic model. Decision tree design. Based on German healthcare system. Clinical data from RCT in France (Meaume 2012).
Augustin states UrgoCell Contact as a comparator, Meaume states UrgoTul Absorb.
Model shows an effect-adjusted cost advantage of €485.64 for UrgoStart over an 8 week treatment period. Although the cost per patient of UrgoStart is greater than the comparator over an 8 week period, the higher response rate results in a lower cost per responder.
Price and resource use data taken from real-world German sources. Sensitivity analysis allows exploration of the inputs and their impact. Limitations: Short treatment time of 8 weeks, wound healing not reached. German system results may not translate to NHS. Study supported by Urgo Medical and authors have received consultancy fees from Urgo.
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UrgoStart for chronic wounds (MIB82)
Maunoury 2012.
UrgoStart vs. Neutral foam Markov model cost- dressing effectiveness without NOSF. study.
UrgoStart is presented as more effective (life years without ulcer(s) gained and quality adjusted life years (QALYs) gained) and less costly than neutral foam dressings.
Monte Carlo simulation of 1000 patients.
Strengths: Health insurance and health care systems (of France) taken into account. Sensitivity analysis performed. Limitations: Conference abstract only. No information on source of clinical data or duration of follow up. French system results may not translate to NHS system. One author
France.
was a employed by the manufacturer of UrgoStart. Taylor 2012. Economic model. Markov model. NHS perspective. Clinical data from RCT in France (Meaume
UrgoStart vs. Neutral foam dressing without NOSF.
UrgoStart was cost saving by £1,812 per patient over a one year period. Main cost saving is reduced nurse time due to faster healing.
Small quality of life improvement was modelled for UrgoStart over Assumes 3 neutral foam dressing, due to dressing increased number of healed changes per wounds. week for each arm.
2012).
Strengths: Appropriate sources for clinical and cost inputs. Model time horizon of one year. NHS perspective. Sensitivity analysis for number of dressing changes. Includes recurrence of wounds. Limitations: Clinical data is from France, possibly different practice from UK. Clinical data limited to 8 weeks duration.
Strengths and limitations of the evidence Overall there was limited robust evidence on the effectiveness of UrgoStart to treat chronic wounds, although the 2 RCTs, Meaume et al. (2012) and Schmutz et al. (2008), were generally welldesigned. The method of randomisation was not reported in Schmutz et al. (2008); and in both studies wounds were not followed to complete closure.
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UrgoStart for chronic wounds (MIB82)
All 4 clinical studies were multicentre studies, which may have meant that each centre had a small number of patients. There were likely to be differences between the participating centres in methods of treatment and assessment. None of the studies provided evidence on the use of UrgoStart in community settings. Only 1 of the 3 economic studies (Augustin et al. 2016) was published as a full paper. This was based on RCT data from Meaume et al. (2012) with real-world costs for German practice, and was well-described. The main limitation was the short time duration of 8 weeks, which for most patients would not be long enough to reach wound healing. The study by Taylor (2012) was also based on RCT data from Meaume et al. (2012) and used UK NHS costs. Although the clinical data was for 8 weeks, the model was extended to 1 year based on this data, showing the economic impact of wounds that do not heal over a long length of time. The Maunoury et al. (2012) study was only available in abstract form and did not contain enough information for full evaluation. All the economic evaluations considered the impact of UrgoStart compared to non-protease modulating dressings. Both RCTs and all 3 economic studies were supported by Urgo Medical or included company employees as authors.
Recent and ongoing studies A search of Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform for 'urgostart or urgo' found the following relevant result: NCT01717183 Assessment of the efficacy and safety of a new wound dressing in the local treatment of diabetic foot ulcers. This trial is now complete, but results have not yet been presented.
Specialist commentator comments The specialist commentators noted that more evidence would be useful, to support the claims of UrgoStart. In addition, more clarity was needed about which patients would benefit most from UrgoStart, and the appropriate duration of treatment before switching to a cheaper product. The minimum recommended use of 8 weeks was queried by 2 commentators, one of whom felt that matrix metalloproteinases would be reduced before this time. It was noted that an alternative protease inhibitor dressing, Promogran, is intended to be used only after the wound has been tested to identify raised protease activity. One commentator suggested
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UrgoStart for chronic wounds (MIB82)
that because the manufacturer states that this test is not needed for UrgoStart, there is a risk that UrgoStart could be overused. One commentator highlighted that additional treatment factors in the studies, such as compression bandaging and debridement, may have a clinical impact aside from the choice of dressing used.
Specialist commentators Comments on this technology were invited from clinical experts working in the field and relevant patient organisations. The comments received are individual opinions and do not represent NICE's view. The following clinicians contributed to this briefing: Professor Peter Vowden, Honorary Visiting Professor of Wound Healing Research, University of Bradford and Honorary Consultant Vascular Surgeon Bradford Teaching Hospitals NHS Foundation Trust. No conflict of interest. Mrs Gail Powell, Clinical Nurse Specialist, Wound Care Service, Bristol Community Health CIC. No conflict of interest. Mr Bill Cox-Martin, Clinical Nurse Specialist, Pressure Ulcer Outreach Service, Salisbury NHS Foundation Trust. No conflict of interest. Mrs Nicci Aylward Wotton, Nurse Consultant, Cornwall Partnership NHS Foundation Trust. Nicci has had a support and training agreement with Urgo. Professor Michael Clark, Professor of Wound Study, Birmingham City University; Director of the Welsh Wound Network, Commercial Director Welsh Wound Innovation Centre. Michael is a consultant to the Welsh Wound Innovation Centre and to several wound care companies (but not to the manufacturer of UrgoStart).
De Devvelopment of this briefing This briefing was developed for NICE by Cedar. The interim process and methods statement sets out the process NICE uses to select topics, and how the briefings are developed, quality-assured and approved for publication. ISBN: 978-1-4731-2115-7
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