A prospective randomised trial of four-layer versus short stretch compression bandages for the treatment of venous leg ulcers. A randomised controlled trial of micronised purified flavonoid fraction vs placebo in patients with chronic venous disease. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. The impact of micronized purified flavonoid fraction on the treatment of acute haemorrhoidal episodes. Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency. Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers. Randomized clinical trial of honey-impregnated dressings for venous leg ulcers. Prospective, multicenter study of managing lower extremity venous ulcers.
This trial was undertaken to examine the safety and efficacy of four-layer compared with short stretch compression bandages for the treatment of venous leg ulcers within the confines of a prospective, randomised, ethically approved trial. Fifty-three patients were recruited from a dedicated venous ulcer assessment clinic and their individual ulcerated limbs were randomised to receive either a four-layer bandage (FLB)(n = 32) or a short stretch bandage (SSB)(n = 32). The endpoint was a completely healed ulcer. However, if after 12 weeks of compression therapy no healing had been achieved, that limb was withdrawn from the study and deemed to have failed to heal with the prescribed bandage. Leg volume was measured using the multiple disc model at the first bandaging visit, 4 weeks later, and on ulcer healing. Complications arising during the study were recorded. Data from all limbs were analysed on an intention to treat basis; thus the three limbs not completing the protocol were included in the analysis. Of the 53 patients, 50 completed the protocol. At 1 year the healing rate was FLB 55% and SSB 57% (chi 2 = 0.0, df = 1, P = 1.0). Limbs in the FLB arm of the study sustained one minor complication, whereas SSB limbs sustained four significant complications. Leg volumes reduced significantly after 4 weeks of compression, but subsequent volume changes were insignificant. Ulcer healing rates were not influenced by the presence of deep venous reflux, post-thrombotic deep vein changes nor by ulcer duration. Although larger ulcers took longer to heal, the overall healing rates for large (> 10 cm2) and small (10 cm2 or less) ulcers were comparable. Four-layer and short stretch bandages were equally efficacious in healing venous ulcers independent of pattern of venous reflux, ulcer area or duration. FLB limbs sustained fewer complications than SSB. to evaluate the efficacy of a micronised purified flavonoid fraction (MPFF) in the treatment of chronic venous disease (CVD).
                prospective double blind, randomised, control study. PATIENTS and
                one hundred and one patients with symptomatic CVD were randomly allocated to treatment for 60 days with either MPFF (51 patients) or placebo (50 patients) 500 mg twice daily. There were 28 men and 73 women, aged 22-65 years (mean age 48 years). No difference regarding age, gender, clinical class or duration of symptoms was recorded between the treatment and placebo groups. A global score for evaluation of symptoms was used. Patients were investigated with plethysmography (foot-volumetry) and duplex-ultrasonography before and after the treatment period. For statistical comparison Cochran-Mantel-Haenszel test, two-sided Student t-test and covariance analysis were used and p<0.05 was regarded significant.
                improvement of the global score of symptoms was reported by 21 patients in the MPFF group and by 16 in the placebo group (N.S.). For the whole groups, no significant differences were recorded before and after treatment regarding foot-volumetric or ultrasonographic parameters. On the other hand, in patients with edema (20 in the MPFF group, 23 in the placebo group) ultrasonographic reflux time was significantly reduced for those in the treatment group (p=0.03). This finding did not correlate to clinical symptoms.
                in this study, MPFF did not change the symptoms of CVD, except night cramps. A secondary finding was reduced reflux times in patients with oedema, although no ultrasonographic or foot-volumetric parameters changed significantly for the whole group. The role of MPFF in treatment of patients with CVD needs to be further analysed in a large population.
                Copyright 2002 Harcourt Publishers Limited. To test the safety, efficacy, and immunological impact of a cultured allogeneic human skin equivalent (HSE) in the treatment of venous ulcers.
                Prospective, randomized study.
                Multicenter study in the outpatient setting.
                Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE. The patients were evaluated for HSE safety, complete (100%) ulcer healing, time to wound closure, wound recurrence, and immune response to the HSE.
                The study was completed as planned in 293 randomized patients.
                Treatment with HSE was more effective than compression therapy in the percentage of patients healed by 6 months (63% vs 49%; P=.02, Fisher exact test, 2-tailed) and the median time to complete wound closure (61 days vs 181 days; P=.003, log-rank test). Treatment with HSE was superior to compression therapy in healing larger (> 1000 mm2; P=.02) and deeper ulcers (P=.003) and ulcers of more than 6 months' duration (P=.001). Occurrence of adverse events was similar in both groups. No symptoms or signs of rejection occurred in response to treatment with HSE, and no HSE-specific immune responses were detected in vitro to bovine collagen or to alloantigens expressed on keratinocytes or fibroblasts.
                Treatment with HSE healed venous ulcers more rapidly and in more patients than compression therapy alone. There was no clinical or laboratory evidence of rejection or sensitization in response to HSE application. These data suggest that HSE represents a significant advance in the treatment of venous ulcers, particularly those that are difficult to heal. Patients with acute bleeding from internal haemorrhoids often have to be referred by the general practitioner to the surgeon for definitive treatment with invasive outpatient procedures. At the initial consultation, patients frequently seek postponement of immediate surgery to a more convenient time. Effective and rapid non-invasive control of acute bleeding could be of practical use in scheduling surgery to a time convenient to both patient and surgeon.
                In a 90-day randomized, double-blind study treatment with a micronized purified flavonoid fraction (MPFF) was compared with placebo, in 100 outpatients who presented for treatment of acute internal haemorrhoids of less than 3 days' duration. The primary endpoint was cessation of bleeding on the third day of treatment.
                Of 50 patients randomized to each group, acute bleeding ceased by the third day in 40 (80 per cent) who received MPFF compared with 19 (38 per cent) who had placebo (P < 0.01). Mean(s.d. ) duration of acute bleeding from onset to cessation of 4.9(1.6) days was 2.1 (95 per cent confidence interval 1.2-2.9) days less than that in patients receiving placebo (P < 0.01). Continued treatment in patients with no bleeding prevented a relapse in 30 of 47 patients, compared with 12 of 30 receiving placebo (P < 0.05).
                Patients with acute internal haemorrhoids treated with MPFF had rapid cessation of bleeding and a reduced risk of relapse. This could be of value in the more convenient timing of treatment with invasive outpatient procedures. To evaluate the efficacy and the tolerability of micronized purified flavonoid fraction (MPFF) on symptoms and signs of acute haemorrhoidal disease (HD).
                Patients experiencing an acute HD episode for less than 48 h were enrolled in this randomized, double-blind, placebo-controlled study (n = 90 in two hospital-based study centres in Beijing). One group received MPFF, six tablets per day for 4 days followed by four tablets per day for 3 days and the other a placebo. Symptoms and signs of HD were assessed by blinded observers at day 0 (D0), day 4 (D4), and day 7 (D7) on a 4-point severity grading scale (from 1 = absent to 4 = severe). A two-way variance analysis was performed for comparison between groups.
                Forty-nine patients (49) in the MPFF group and 41 in the placebo group (mean age 43.2 years [range 18-76 years]), percentage of male gender 54.4%, mean time from onset of acute episode 45.3 h (range 16-48 h) were included in this analysis. No significant differences between groups were seen at baseline in terms of age, gender, and frequency and intensity of symptoms, except for oedema, whose frequency and severity was significantly greater in the MPFF group (p = 0.024). During the 7-day treatment, there was a significant difference in favour of MPFF in the evolution of pain and oedema (p < or = 0.001 at D7) and in bleeding (p = 0.021 at D4, and p = 0.047 at D7). The appreciation of global efficacy by patients (p = 0.007) or investigators (p = 0.006) also favoured MPFF. Blood pressure, heart rate and laboratory parameters remained within normal ranges and were not modified during the study in either group. No patient had to stop the treatment owing to adverse events and only one patient reported gastrointestinal discomfort.
                MPFF significantly reduced the extent of pain and bleeding in the selected subjects of this study with acute haemorrhoids. The tolerability was similar in patients receiving MPFF to that in patients receiving a placebo during the 7-day duration of the treatment.MPFF can be considered an effective and well-tolerated agent in the treatment of acute episodes of haemorrhoids. Epidemiological data show that standard compression therapy for leg ulceration in chronic venous insufficiency (CVI) often fails to effectively improve patients' condition. This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients.
                Patients of about 65 years were included, with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs, Doppler ankle/arm pressure index > 0.9, and no recent history of skin graft. Controls (n=68) remained on compression alone while the tested group (n=82) also received Daflon 500 mg 2 tablets/day during 6 months. Treatment could be stopped as soon as the reference ulcer appeared fully healed. Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination. Variations of the ulcer surface, appearance of the skin, and clinical symptoms of CVI were the secondary criteria.
                Only 7% of Daflon 500 mg patients necessitated the full 6 month therapy. Whatever the lesion size, from W8 significantly more healed ulcers were observed under Daflon 500 mg (p=0.004), and the ulcer surface was more reduced (p=0.012). For large ulcers, the rate of healing was approximately 2-fold higher with Daflon 500 mg, and the percentage of ulcers healed before W24 was significantly higher (p=0.008). Heavy leg sensation was significantly improved by Daflon 500 mg from W4 (p < 0.05). No treatment-related side effects were reported and the acceptability was considered excellent by 85% of Daflon 500 mg patients.
                Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI, with a good acceptability. Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers.
                Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers.
                Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment.
                No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different.
                CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs. The efficacy of honey as a treatment for venous ulcers has not been evaluated, despite widespread interest. This trial aimed to evaluate the safety and effectiveness of honey as a dressing for venous ulcers.
                This community-based open-label randomized trial allocated people with a venous ulcer to calcium alginate dressings impregnated with manuka honey or usual care. All participants received compression bandaging. The primary outcome was the proportion of ulcers healed after 12 weeks. Secondary outcomes were: time to healing, change in ulcer area, incidence of infection, costs per healed ulcer, adverse events and quality of life. Analysis was by intention to treat.
                Of 368 participants, 187 were randomized to honey and 181 to usual care. At 12 weeks, 104 ulcers (55.6 per cent) in the honey-treated group and 90 (49.7 per cent) in the usual care group had healed (absolute increase 5.9 (95 per cent confidence interval (c.i.) -4.3 to 15.7) per cent; P = 0.258). Treatment with honey was probably more expensive and associated with more adverse events (relative risk 1.3 (95 per cent c.i. 1.1 to 1.6); P = 0.013). There were no significant differences between the groups for other outcomes.
                Honey-impregnated dressings did not significantly improve venous ulcer healing at 12 weeks compared with usual care. Registration number: ISRCTN 06161544 (http://www.controlled-trials.com).
                2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Seventy patients with 90 venous ulcers were randomly assigned to hydrocolloid or conventional dressing and compression therapy at four study centers. The ulcers had been present for a mean of 47.8 in the control and 46.2 weeks in the treatment group and 42% of all patients had recurrent ulcers. Ulcers treated with hydrocolloid dressings reduced 71% and control treated wounds reduced 43% in area after 7.2 weeks of treatment. Thirty-four percent of all ulcers healed. Mean time to healing was 7 weeks for the hydrocolloid dressing group and 8 weeks for the control group. Most ulcers were less painful at final evaluation, but reduction in pain was more pronounced in hydrocolloid-dressed ulcers (p = 0.03). At baseline as well as during follow-up, significant differences between study centers were observed. Ulcers in patients in the United Kingdom were larger and less likely to heal (p = 0.001). Size of the ulcer at baseline was associated with treatment response and time to healing (p = 0.002). Percent reduction in ulcer area after 2 weeks was also correlated with treatment outcome (p = 0.004) and time to healing (p = 0.002). When all treatment outcome predictors were analyzed together, only percent reduction in area after 2 weeks remained statistically significant (p = 0.002), with percent reduction during the first 2 weeks of treatment > 30% predicting healing.
Although the overall estimate of the number of healed ulcers appeared to show a significant effect in favour of flavonoids (both MPFF and HR), this result needs to be interpreted cautiously, as most of these trials were poorly reported, and so had an unclear risk of bias for randomisation, allocation concealment, blinding and methods for addressing incomplete outcome data. There was also a possibility of publication bias.