A prospective randomised controlled trial and economic modelling of antimicrobial silver dressings versus non-adherent control dressings for venous leg ulcers: the VULCAN trial.

OBJECTIVE: To examine the effectiveness and cost-effectiveness of antimicrobial silver-donating dressings for venous leg ulcers compared with simple non-adherent (also known as low-adherent) dressings. DESIGN: A pragmatic, prospective randomised controlled trial (RCT) and cost-effectiveness analysis of silver-donating versus low-adherent dressings in the treatment of venous leg ulcers. A non-randomised observational group was also recruited. SETTING: Primary and secondary care services in the north and south of England (Sheffield and Exeter). PARTICIPANTS: Consenting patients with active ulceration of the lower leg that had been present for a period of greater than 6 weeks. INTERVENTIONS: Patients were randomised to receive either a silver-donating or non-silver low-adherent dressing applied beneath compression bandages or hosiery. The choice of dressing within these groups was left to clinician preference. Evaluation was by clinical assessment, supplemented by evaluation of quality of life and cost-effectiveness. MAIN OUTCOME MEASURES: The primary outcome measure was complete ulcer healing at 12 weeks in the index limb. Secondary measures were costs and quality-adjusted life-years (QALYs), cost-effectiveness, time to healing, and recurrence rate at 6 months and 1 year. RESULTS: In total, 304 participants were recruited to the clinical trial: 213 to the RCT and 91 to the observational arm. Within the RCT 107 were randomised to antimicrobial dressings and 106 to the control dressings. There were no significant differences (p > 0.05) between the two groups for the primary outcome measure of proportion of ulcers healed at 12 weeks (59.6% for silver and 56.7% for control dressings). The overall median time to healing was also not significantly different between the two groups (p = 0.408). A total of 24 patients had recurrent ulcers within 1 year; the recurrence rates of 11.6% (n = 11) for the antimicrobial and 14.4% (n = 13) for the control dressings were not significant. Mean utility valuations for both the EuroQol 5 dimensions (EQ-5D) quality of life questionnaire and Short Form 6 dimensions (SF-6D) utility index showed no differences for either group at 1, 3, 6 or 12 months. Compared with the control group, the antimicrobial group had an incremental cost of 97.85 pounds and an incremental QALY gain of 0.0002, giving an incremental cost-effectiveness ratio for the antimicrobial dressings of 489,250 pounds. Cost-effectiveness modelling of the results of the RCT showed that antimicrobial dressings were not cost-effective. CONCLUSIONS: No significant differences in either primary or secondary end points were found between the use of antimicrobial silver-donating dressings and the control group of low-adherent dressings. Modelling showed that antimicrobial silver dressings were not cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72485131.

Randomized controlled trial and cost-effectiveness analysis of silver-donating antimicrobial dressings for venous leg ulcers (VULCAN trial).

BACKGROUND: Antimicrobial silver dressings are used beneath graduated compression in the treatment of venous ulceration. There is little information on whether their use is effective. This was a prospective randomized trial and cost-effectiveness analysis of silver-donating versus non-silver low-adherence dressings in the treatment of venous leg ulcers. METHODS: Patients were randomized between the two types of dressing. The primary outcome measure was complete ulcer healing at 12 weeks. Secondary outcomes included time to healing, quality of life and cost-effectiveness. RESULTS: A total of 213 patients were recruited. There was no difference between the dressings in the proportion of ulcers healed at 12 weeks (59.6 per cent for silver and 56.7 per cent for control dressings). Mean utility scores for the EuroQol 5D and Short Form 6D were similar in both groups at 1, 3, 6 and 12 months. Compared with the control group the antimicrobial group had an incremental cost of pounds sterling 97.85 and an incremental quality-adjusted life year gain of 0.0002, giving an incremental cost-effectiveness ratio of pounds sterling 489 250 for the antimicrobial dressings. CONCLUSION: No significant differences were found in either primary or secondary endpoints. There was no evidence to support the routine use of silver-donating dressings beneath compression for venous ulceration. REGISTRATION NUMBER: ISRCTN 72485131 (http://www.controlled-trials.com).

A systematic review of compression hosiery for uncomplicated varicose veins.

OBJECTIVE: Compression hosiery is widely used in the prevention and management of symptoms related to varicose veins. However, there are still gaps and questions in relation to its benefit. This review seeks to examine the current evidence regarding the effectiveness of compression hosiery in the treatment of varicose veins. METHOD: Prospective, randomized controlled trials (RCTs) evaluating compression hosiery in the treatment of varicose veins were sought. Where RCTs were unavailable other evidence was included. Studies were included if they evaluated the application of compression to patients with a diagnosis of varicose veins. Twelve electronic bibliographic databases and 18 internet-based research resources were searched. Inclusion or exclusion of trials was decided by two reviewers acting independently. RESULTS: The search strategy identified 25 studies. Eleven were RCTs or systematic reviews, 12 non-randomized studies and two guidelines. No consensus was found regarding the class of compression needed for the effective management of varicose veins. Wearing compression improved symptom management, but could be confounded by the exclusion of high number of non-compliant patients within the trials. Wearing compression to slow the progression, or prevent the reoccurrence of varicose veins could not be supported by the current published evidence. CONCLUSION: The evidence for the benefit of compression hosiery for varicose veins was equivocal. The published literature was often contradictory and had methodological flaws.

Dressings for healing venous leg ulcers.

BACKGROUND: Venous leg ulcers, sometimes called varicose or stasis ulcers, are a consequence of damage to the valves in the veins of the legs, leading to raised venous pressure. Venous ulcers are characterised by a cyclical pattern of healing and recurrence. The main treatment is the application of compression, either in the form of compression bandages or hosiery. Dressings are usually applied beneath the compression to aid healing, comfort and to control exudate. Wounds heal quicker in a moist environment and dressings are used to absorb excess fluid or retain fluid in an otherwise dry wound in order to achieve a 'moist wound environment'. There are a large number of dressing products and types available. It is unclear whether particular dressings aid healing of leg ulcers. OBJECTIVES: To assess the effectiveness of wound dressings for the treatment of venous leg ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (April 2006) and CENTRAL (issue 1, 2006) and several other electronic databases (up to April 2005). Manufacturers of dressing products were contacted for unpublished studies. SELECTION CRITERIA: Randomised controlled trials that evaluated dressings for the treatment of venous leg ulcers. There was no restriction in terms of source, date of publication or language. Ulcer healing was the primary endpoint. DATA COLLECTION AND ANALYSIS: Data from eligible studies were extracted and summarised using a data extraction sheet by two authors independently. MAIN RESULTS: 42 randomised controlled studies were identified that met the inclusion criteria. The main dressing types that were evaluated were hydrocolloids (n = 23), foams (n = 6), alginates (n = 4), hydrogel dressings (n = 6) and a group of miscellaneous dressings (n = 3). In none of the comparisons was there evidence that any one dressing type was better than others in terms of number of ulcers healed. Current evidence does not suggest that hydrocolloids are more effective than simple low adherent dressings used beneath compression (9 trials; relative risk for healing with hydrocolloid 1.09 (95% CI 0.89 to 1.34)). For other comparisons there was insufficient evidence. AUTHORS' CONCLUSIONS: The type of dressing applied beneath compression has not been shown to affect ulcer healing. For the majority of dressing types there was insufficient data to allow us to draw strong conclusions except for hydrocolloid compared with a low adherent dressing. The result of the meta-analysis indicate no significant difference in healing rates between hydrocolloid dressings and simple, low-adherent dressings when used beneath compression. Decisions regarding which dressing to apply should be based on local costs of dressings and practitioner or patient preferences.

Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).

OBJECTIVES: To establish the cost-effectiveness of surgery and sclerotherapy for the treatment of varicose veins. DESIGN: Randomised controlled trials (RCTs) were carried out for conservative treatment, sclerotherapy and surgery for varicose veins. An economic analysis was carried out alongside the randomised trial. Economic modelling was undertaken based on the primary data collection and a literature review (database searches undertaken in April 2000 and updated in March 2001). SETTING: Primary data collection was from a large district general hospital and a teaching hospital both in England over a 2-year period from January 1999. Cost-effectiveness analysis and economic modelling were carried out using an NHS perspective. PARTICIPANTS: A total of 1009 patients were recruited. INTERVENTIONS: Thirty-four patents were randomised in Group 1 (minor varicose veins with no reflux, randomised between conservative treatment and sclerotherapy), 77 in Group 2 (moderate varicose veins with reflux, randomised between surgery and sclerotherapy) and 246 in Group 3 (severe varicose veins with reflux, randomised between conservative treatment and surgery). The remaining 652 patients formed the observational part of the study. MAIN OUTCOME MEASURES: The cost-effectiveness analysis was based on NHS treatment costs for the 2002--3 financial year, and utilities based on the Short Form 6D (SF-6D) preference-based health measure. For the clinical trial, the outcome measures were health-related quality of life (HRQoL) [Short Form with 36 Items (SF-36), EuroQol quality of life questionnaire (EQ-5D), visual analogue scale (VAS) and standard gamble], symptomatic relief, anatomical extent (for which a new classification was developed and validated), patient satisfaction and the incidence of complications. RESULTS: Of the RCTs, only the Group 3 trial was large enough to provide clear results. This showed that surgical treatment produced better results than conservative treatment in terms of HRQoL, symptomatic relief, anatomical extent and patient satisfaction. Clinical outcomes of surgery and sclerotherapy showed significant improvement in the extent of varicose veins, symptomatic and HRQoL parameters. Cost-effectiveness analysis based on the Group 3 trial showed that the surgery produced an estimated discounted benefit of 0.054 quality-adjusted life-year (QALY) over a 2-year period, with an additional discounted cost of pound 387.45, giving an incremental cost-effectiveness ratio (ICER) of pound 7175 per QALY. Economic modelling suggested that surgery produced a still greater benefit when considered with a 10-year time horizon, with an ICER of pound 1936 per QALY. Injection sclerotherapy produced an incremental benefit of approximately 0.044 QALY at a cost of pound 155 when compared with conservative treatment, giving an ICER of pound 3500 per QALY. When surgery was compared with sclerotherapy, surgery produced greater benefit with a lower ICER (showing extended dominance). CONCLUSIONS: Standard surgical treatment of varicose veins by saphenofemoral ligation, stripping and multiple phlebectomies is a clinically effective and cost-effective treatment for varicose veins, with an ICER well below the threshold normally considered appropriate for the funding of treatments within the NHS. Injection sclerotherapy also appears to be cost-effective, but produces less overall benefit, with a higher ICER than surgery for patients with superficial venous reflux. In minor varicose veins without reflux, sclerotherapy is likely to provide a small average benefit with acceptable cost-effectiveness. Research is needed into methods for accurate and acceptable utility evaluations for conditions with relatively minor effect on HRQoL and also for a validated and standardised method of classification for varicose veins.

Randomized clinical trial comparing surgery with conservative treatment for uncomplicated varicose veins.

BACKGROUND: Surgical treatment of medically uncomplicated varicose veins is common, but its clinical effectiveness remains uncertain. METHODS: A randomized clinical trial was carried out at two large acute National Health Service hospitals in different parts of the UK (Sheffield and Exeter). Some 246 patients were recruited from 536 consecutive referrals to vascular outpatient clinics with uncomplicated varicose veins suitable for surgical treatment. Conservative management, consisting of lifestyle advice, was compared with surgical treatment (flush ligation of sites of reflux, stripping of the long saphenous vein and multiple phlebectomies, as appropriate). Changes in health status were measured using the Short Form (SF) 6D and EuroQol (EQ) 5D, quality of life instruments based on SF-36 and EuroQol, complications of treatment, symptomatic measures, anatomical extent of varicose veins and patient satisfaction. RESULTS: In the first 2 years after treatment there was a significant quality of life benefit for surgery of 0.083 (95 per cent confidence interval (c.i.) 0.005 to 0.16) quality-adjusted life years (QALYs) based on the SF-6D score and 0.13 (95 per cent c.i. 0.016 to 0.25) based on the EQ-5D score. Significant benefits were also seen in symptomatic and anatomical measures. CONCLUSION: Surgical treatment provides symptomatic relief and significant improvements in quality of life in patients referred to secondary care with uncomplicated varicose veins.

Surgery versus sclerotherapy for the treatment of varicose veins.

BACKGROUND: Varicose veins are a relatively common condition and account for around 54,000 in-patient hospital episodes per year. The two most common interventions for varicose veins are surgery and sclerotherapy. However, there is little comparative data regarding their effectiveness. OBJECTIVES: To identify whether the use of surgery or sclerotherapy should be recommended for the management of primary varicose veins. SEARCH STRATEGY: Thirteen electronic bibliographic databases were searched covering biomedical, science, social science, health economic and grey literature (including current research). In addition, the reference lists of relevant articles were checked and various health services research-related resources were consulted via the internet. These included health economics and HTA organisations, guideline producing agencies, generic research and trials registers, and specialist sites. SELECTION CRITERIA: All studies that were described as randomised controlled trials comparing surgery with sclerotherapy for the treatment of primary varicose veins were identified. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted and summarised data from the eligible studies using a data extraction sheet for consistency. All studies were cross-checked independently by the reviewers. MAIN RESULTS: A total of 2306 references were found from our searches, 61 of which were identified as potential trials comparing surgery and sclerotherapy. However, only nine randomised trials, described in a total of 14 separate papers, fulfilled the inclusion criteria. Fifty trials were excluded and one trial is ongoing and is due for completion in 2004. The trials used a variety of outcome measures and classification systems which made direct comparison between trials difficult. However, the trend was for sclerotherapy to be evaluated as significantly better than surgery at one year; after one year (sclerotherapy resulted in worse outcomes) the benefits with sclerotherapy were less, and by three to five years surgery had better outcomes. The data on cost-effectiveness was not adequately reported. REVIEWERS' CONCLUSIONS: There was insufficient evidence to preferentially recommend the use of sclerotherapy or surgery. There needs to be more research that specifically examines both costs and outcomes for surgery and sclerotherapy.

Surgery for varicose veins: use of tourniquet.

BACKGROUND: Varicose vein surgery is a common surgical procedure but there is no consensus regarding the best surgical technique. The use of tourniquets during varicose vein surgery has been advocated as a means of reducing the potential for blood loss during the operation. OBJECTIVES: To identify whether the use of a tourniquet should be recommended when undertaking surgery for the management of primary varicose veins. SEARCH STRATEGY: The reviewers searched the Cochrane Peripheral Vascular Diseases Group trials register (last searched November 2001), thirteen electronic bibliographic databases, including the Cochrane Controlled Trials Register (CCTR) (last searched Issue 3, 2001), covering biomedical science, social science, health economic and grey literature (including current research). In addition, the reference lists of relevant articles were checked and various health services research related resources were consulted via the Internet. These included health economics and HTA organisations, guideline producing agencies, generic research and trials registers, and specialist sites. SELECTION CRITERIA: All studies described as randomised controlled trials that examined the use of tourniquets during surgery for patients with primary varicose veins were included. DATA COLLECTION AND ANALYSIS: Data from eligible studies were extracted and summarised independently by two reviewers. All studies were cross-checked independently by the reviewers. MAIN RESULTS: A total of twenty published papers and nineteen studies were identified. Only three of these were randomised controlled trials and were included in the review. Sixteen studies were excluded as they were non-randomised and one was a duplicate study. All three trials had a small sample size and reported the trial design, outcome measures and analysis poorly. There were also variations in the outcome measures used between the trials. In addition, there was no consistency on the reporting of mean and medians for blood loss during the operation. It was therefore not possible to pool the data to perform meta-analysis. However, the reported blood loss when using a tourniquet was between 0 and 16mls compared to between 107 to 133mls when not using a tourniquet (p<0.01). REVIEWER'S CONCLUSIONS: Although there were significant quality issues with the available evidence, the use of a tourniquet would appear to reduce blood loss during surgery. There were no reported differences between the use or non-use of a tourniquet in terms of complications and morbidity. However, the available trials were not of sufficient size to detect rarer complications such as nerve damage.

A systematic review of intra-arterial thrombolytic therapy for lower-limb ischaemia.

METHODS: a search of the major databases was carried out to identify randomised controlled trials of intra-arterial thrombolytic therapy in the treatment of limb ischaemia. The search was limited to English language articles, or those that provided a sufficiently detailed English summary, and to articles published after 1980. In addition, key journals were hand-searched and citations were also reviewed. Two reviewers independently performed data extraction and aggregate outcomes were obtained using a random effects meta-analysis. RESULTS: a total of 34 articles were found, but only 10 were reports of randomised controlled trials. Meta-analysis showed no significant differences between thrombolysis and surgery in terms of major amputation (relative risk (RR) 0.893 95% confidence interval (CI) 0.576, 1.383) and mortality (RR 1.24 95% CI 0.795, 1.9). However, there was an increased risk of haemorrhage with thrombolysis (RR 2.94 95% CI 1.1, 7.9). Sub-group analysis suggests that short-duration occlusions (relative risk reduction (RRR) 72%, numbers needed to benefit (NNB)=3) and occluded grafts (RRR 58%, NNB=4) may benefit from thrombolysis. However, thrombolysis should be avoided in occlusions of greater than 14 days - particularly native vessel occlusions. CONCLUSION: despite the theoretical advantages of thrombolysis, there is still insufficient evidence to justify its widespread use except in graft occlusions and short-duration ischaemia.

A systematic review of compression therapy for venous leg ulcers.

The aim of the study was to determine the relative effectiveness of compression therapies used in the treatment of venous leg ulcers. Randomized controlled trials (RCT) were sought using a search strategy that aimed to identify relevant RCT by searching eight electronic databases (including Medline, Embase and CINHAL), conference proceedings and hand searching key journals. In addition, citations within papers were scrutinized to identify any relevant studies. Suitability for inclusion in this review was determined by a critical appraisal of key determinants of the quality of the trials. Trials that included patients of mixed ulcer aetiology were excluded unless the results of patients with venous disease were reported separately. Data was extracted independently by two reviewers and synthesized quantitatively and qualitatively. Losses to follow-up/withdrawals were assumed to be failures of treatment. A total of 132 articles were identified, and of these eight fulfilled the inclusion criteria. The remaining 126 trials were excluded due to trial design flaws, the inclusion of mixed/arterial aetiology ulcers or because they were non-RCT. Meta-analysis using a random-effects model showed the benefits of multi-layer and elastic compression bandages. It was concluded that more high-quality trials are required and that more emphasis should be placed on economic and quality of life data to try to ascertain the cost-effectiveness and utility of the treatment options available.