Keywords Venous leg ulcer, compression therapy, Tubulcus, acceptance

Transcription

1 12/ Schattauer GmbH Tubulcus -Kompressionstherapie des venösen Ulcus cruris Ergebnisse einer prospektiven Anwendungsbeobachtung W. Vanscheidt 1, R. Kohnen 2, I. Achhammer 3 1 Freiburg, 2 Imerem GmbH, Nürnberg, 3 Innothera GmbH, Sulzburg Schlüsselwörter Ulcus cruris venosum, Kompressionstherapie, Tubulcus, Akzeptanz Zusammenfassung Ziel: Offene prospektive Anwendungsbeobachtung zur Effektivität, Sicherheit und des Wohlbefindens der Patienten während einer dreimonatigen Behandlung des venösen Ulkus mit Tubulcus. Methode: In 40 Zentren in Deutschland wurden 116 Patienten beobachtet. Kriterien waren Ulkusgröße (5 Klassen nach größtem Durchmesser: <2,5, 2,5-5, 5-7,5, 7,5-10, >10cm), Zustand des Ulkus und der periulzerösen Haut zu Beginn und nach 3 Monaten sowie die globale Beurteilung der Wirksamkeit und Verträglichkeit und die Patientenakzeptanz. Ergebnis: Bei 77 Patienten (66,4%) wurde eine vollständige Abheilung oder Reduktion der Größe des Ulkus beobachtet sowie eine signifikante Besserung des Zustands des Ulkus und der periulzerösen Haut. Dem entspricht die globale Beurteilung der Effektivität als gut oder sehr gut. Die Verträglichkeit sowie die Erfahrung der Patienten mit dem Tragen war ebenfalls gut oder sehr gut. Schlussfolgerung: Die Kompressionstherapie des Ulcus cruris mit Tubulcus in der täglichen Praxis ist effektiv und wird von den Patienten gut vertragen und gut akzeptiert. Phlebologie 2004; 33: 12 6 Keywords Venous leg ulcer, compression therapy, Tubulcus, acceptance Summary Aim: Open prospective observeillance study of efficacy, tolerability and subjective well-being of patients during therapy of 3 months of the venous ulcer with Tubulcus. Method: Observation of 116 patients in 40 centres in Germany. Parameters observed were ulcer size (categorized in 5 classes of maximal diameter: <2.5, 2.5-5, 5-7.5, , >10 cm), clinical appearance of the ulcer and the surrounding skin at start and after 3 months and a global judgement of efficacy and tolerance as well as patients perception of well-being. Results: In 77 patients (66.4%) complete healing of the ulcer or decrease of the size was documented as well as a significant amelioration of appearance of the ulcer and the surrounding skin. Correspondingly the global judgement of efficacy was good or very good. Tolerance as well as patients experience with wearing Tubulcus was documented as good or very good. Conclusion: Compression therapy of venous ulcers with Tubulcus in daily practice is effective and well tolerated and accepted by the patients. Tubulcus compression therapy of venous leg ulcer results of a large prospective post-marketing observeillance study Mots clés Ulcère veineux, traitement compressif, Tubulcus, acceptabilité Résumé Objet: Etude observationelle en ouvert de l efficacité, la tolérance et l acceptabilité du traitement d un ulcère veineux par Tubulcus pendant 3 mois. Méthode: Observation de 116 patients dans 40 centres en Allemagne. Critères retenus: taille de l ulcère (5 classes selon le diamètre maximal: <2.5, 2.5-5, 5-7.5, , >10 cm), l aspect de l ulcère et de la peau périulcéreuse au début et à la fin du traitement, jugement global de l efficacité et de la tolérance par les médecins et les patients ainsi que l acceptabilité des patients. Résultats: Guérison complète ou diminution de la taille de l ulcère chez 77 patients (66.4%), amélioration significative de l aspect de l ulcère et de la peau périulcéreuse. C est en accord avec le jugement de l efficacité comme bon ou très bon. La tolérance ainsi que l expérience des patients ont été jugé bon ou très bon. Conclusion: Le traitement compressif de l ulcère veineux par Tubulcus, dans la pratique quotidienne, est efficace et très bien toléré et acceptée par les patients. Tubulcus dans le traitement compressif de l ulcère veineux des jambes résultat d une grande étude post marketing de surveillance Venous leg ulcers affect at least 0.2% of the population in the developed world which is considered as a significant socio-oeconomic disorder (1, 13, 15, 18, 19). The aim of the treatment of venous ulcers is to ensure healing of the wound and prevention of recurrence. Independently of the local wound treatment, either alone or combined with surgery, compressive therapy is the recognized as gold standard in the treatment of venous ulcers, usually performed with bandages (2, 3, 8). The correct application of those bandages must be learned and continuously trained (12). Its quality depends of the skill of the fitter and is when patients do it themselves negatively influenced by individual physical conditions like obesity, arthritis, and general immobility. In general practice bandages are often poorly positioned, they may be too loose and slip or too tight causing constriction. Therefore, patients not only experience their disease as negative but also the treatment. This causes poor compliance with compressive therapy and consequently delayed healing (11). To overcome those problems, different tubular compression devices and stockings were developed. One of these is Tubulcus, a ready-made tubular compression device (Fig. 1), with no heel and open-toed exerting a well-defined constant pressure over time (4-6). It can be applied without the need for a qualified fitter, and putting on is facilitated by a special positioner. Post-Marketing Observational Studies (PMOS) allow the observation of a disease process and its treatment under naturalistic conditions.the aim of this study was the doc- Eingegangen: 12. August 2003; angenommen: 16. Oktober 2003

2 13/25 Tubulcus -Kompressionstherapie umentation of efficacy and tolerability of the Tubulcus therapy of the venous leg ulcer as well as the patients subjective well-being during a 3-month period in daily practice. Patients, material, methods Design This study was performed as prospective, open-label, naturalistic post-marketing observeillance study (PMOS). A total of 40 physicians in Germany (general practitioners and specialists in dermatology and/or phlebology) participated in the study and documented data for 116 patients. The observation period was supposed to cover 3 months and started with the first application of Tubulcus. Any other compression treatment was discontinued at the beginning of the study. According to the principles of PMOS no selection criteria for including patients were established. However, the physicians documented treatments of patients with venous leg ulcer and the need of a compressive therapy with Tubulcus. The treating physician made sure that the indication and contraindications (arterial occlusive disease stage II-IV or arterial blood pressure index <0.9, decompensated heart failure) for the treatment with Tubulcus were respected and the correct size for each individual patient determined. The data collection was conducted between September 2000 and October At inclusion, patient characteristics, diagnosis of the venous insufficiency, prior compressive therapy, leg circumferences, concomitant treatment of the ulcer other than compressive therapy, appearance of the ulcer (determination of size) and the surrounding skin and concomitant diseases were documented. After about 12 weeks of treatment (or earlier in case of complete healing) documentation of ulcer size, leg circumferences, appearance of the ulcer and the surrounding skin, global assessment of efficacy and tolerability by physicians and patients, complete duration of wearing Tubulcus and frequency of changes was performed. Additionally a questionnaire was used to measure patients convenience with Tubulcus treatment. Statistics Fig. 1 Tubulcus Statistical analysis was performed descriptively, presenting frequency distributions and descriptive statistics for quantitative data (mean, standard deviation, median, minimal and maximal values). If applicable, changes in ordinal or metric data between baseline and final assessments were compared by paired tests (signed rank U-test), in case of qualitative data, by chi 2 -symmetry test (McNemar test for 2 2, Bowker test for n n tables) were used. Values p <0.05 for these comparisons indicate that there was a non-random change between both assessments in the variable affected; such findings are explorative in nature and limited to the description of the data of this PMOS. Results Patients Altogether 116 patients with venous leg ulcer were observed. About one third were men (35.5%) and two thirds were women (63.8%); mean age was 65.6 years (range years). Post thrombotic venous ulcer was diagnosed in 38% of the patients. The most frequent concomitant diseases other than CVI were diabetes mellitus (11.2%), hypertension (9.5%), coronary heart disease (6.0%) and obesity (6.9%). The majority of patients (82%) had previous treatment with compressive therapy and almost all had additional local treatment (93.1%) of the ulcer. The ulcer treated was located at the left leg in 52.6% and at the right leg in 44.0%. It was situated lateral malleolar in 22.4% and medial malleolar in 67.2% of the patients legs. Treatment The mean duration of the treatment with Tubulcus was 67.7 ± 28 days (median: 76 days, maximum: 120 days). The determination of the adequate size of Tubulcus corresponding to the respective circumferences was no major practical problem. As expected, smaller sizes were more frequently used for women (S: 17.6%, M: 29.2%, L: 28.4%, XL: 12.2%, XXL: 0%) and larger ones for men (S: 2.4%, M: 24.4%, L: 41.5%, XL: 19.5%, XXL: 7.3%). Application of the Tubulcus or slipping of wound dressing during application was no problem for the physicians but for a few patients it was difficult to put it on by themselves. Tubulcus was worn at day and night by half of the patients (47.4%). In 31% of the patients it was changed daily, in half of the patients every second day or twice a week and in a few once a week (6%). Reasons for changes were mainly routine treatment (78.5%) or necessary due to heavy exsudation (17.2%). Treatment with Tubulcus was continued after the end of the observational period in 73 patients (62.9%), including 21 patients with their ulcer completely healed.

3 14/26 Vanscheidt, Kohnen, Achhammer For the 19 patients (out of 29) who had their treatment stopped at the end of the study, the reasons were commented as follows: complete healing (8 patients), adverse event (3 patients), worsening of the ulcer (2 patients), and application difficulties with the Tubulcus (5 patients). Tab. 1 Change of maximal ulcer size (categorial analysis): percentages (in parenthesis) related to the total number of patients per category at baseline ( 1 no information on ulcer size available for 4 patients) Efficacy Ulcer size The largest diameter of the ulcer was measured at baseline and at final visit and was documented according to the classification into five classes of maximal diameter ( 2.5, >2.5-5, >5-7.5, >7.5-10, >10 cm). The comparison of ulcer sizes at baseline and at final assessment revealed complete healing in 25.9%, improvement by at least one category of ulcer size in 42.9%, stable condition in 29.5%, and worsening in 1.8% (2 patients). In total, 77 patients (68.8%) experienced complete healing or reduction of size of their ulcer (p<.0001, Bowker test). Ulcer sizes of <5 cm found in the majority of patients at start of therapy (70.6%) had a better chance to heal or improve with Tubulcus therapy than larger sized ulcers (Tab. 1). Oedema The circumference of the ankle decreased by 0,72 ± 1.7 cm (ranging from -7.5 to cm) between baseline (24.8 ± 3.6 cm) and final assessment (24.1 ± 3.5 cm). Also the circumference of the calf was by 1.1 ± 2.0 cm (range to +5.9 cm) smaller at the final assessment (36.2 ± 4.8 cm) than at the time of starting Tubulcus treatment (37.2 ± 4.6 cm). Though the changes seem small in size, the p-values, which are associated with the pre-post comparison (p <.0001, Wilcoxon rank sum U-test, for both variables), indicate that these changes are not at random. Clinical appearance of the ulcer and the surrounding skin To characterise in more detail the appearance of the ulcer, it was documented whether it was granulated, fibrous, without reaction, exsudative or superinfected. The parameters of the ulcer s appearance changed in a favourable manner: granulation increased, all other signs decreased.all these changes were associated with values p <.0001 in pre-post chi 2 McNemar symmetry tests. For 17.2% of the patients a normal surrounding skin was documented at baseline. The global rate of erythemas did not change during the observational period which, however, is due to equal rates of appearance and disappearance. In contrast, the presence of oedema, eczema and inflammation decreased to very low rates at the final assessment (p <.0001, McNemar test) (Tab. 2). Global rating of efficacy The efficacy of Tubulcus treatment was judged slightly more favourable by the treating physician than by the patients: 77.6% of the physicians and 70.7% of the patients estimated the efficacy globally as very good or good. The categories bad or very bad occurred in 7 patients (both by physician and patients). Tolerability, adverse events Three fourth of physicians and patients rated the tolerability of the compressive Tab. 2 Changes in appearance of the ulcer and the surrounding skin between baseline and final assessment (percentage related to all n = 116 patients; patients without the respective quality not represented; p-values associated to the Mc-Nemar symmetry test; n.d.: not done due to low number of patients concerned)

4 15/27 Tubulcus -Kompressionstherapie therapy as very good or good. Eight patients (6.9%) stated treatment as bad or very bad compared to 5 physicians (4.3%). Only 3 adverse events were reported in 3 patients: One women (age: 83 years) was hospitalised for inguinal hernia after two weeks of treatment. In a 74 year-old men treatment was stopped after 30 days for dysaesthesia associated with itching, prickling and feeling of pressure, and in the third patient (age: 59 years) the treatment with Tubulcus was not continued after complete healing after 35 days and thereafter was reported as an adverse event, consisting in itching of the leg (an allergy could not be excluded). A relationship to Tubulcus treatment was suspected in the latter two patients. In one further men (82 years) treatment was stopped after 35 days because his ulcer worsened. Subjective experiences At the final visit, patients were asked to complete a questionnaire and to report Tab. 3 Patients experience with Tubulcus treatment ( 1 data from 11/13 patients missing) their subjective perspective on wearing the Tubulcus. The patients were asked about their experience concerning flexibility of the ankle region, slipping of Tubulcus, problems with daily hygiene, appearance of Tubulcus on the leg and comfort in general of wearing it. The results are given for all patients in the Table 3. The patient ratings indicate a proportion of at least two thirds who reported positive and very positive experiences after long-term treatment with the Tubulcus.16 patients evaluated the flexibility in the ankle joint as bad or very bad. It cannot be differentiated whether these problems were due to particular conditions of the ankle joint already present before or associated with the compressive treatment as no data at baseline are available. Only in one woman slipping of the Tubulcus was a severe problem. Men differed from women with respect to daily hygiene: Women had more often (mainly moderate) problems than men. Also when asked for the appearance of the Tubulcus on the leg, several women did not use the two most favorable categories but described that item more frequent than men as acceptable. Finally, with regard to wearing of the Tubulcus only five patients described this quality aspect as less convenient. Discussion This post-marketing observeillance study (PMOS) was conducted to document the treatment of venous leg ulcers with Tubulcus compressive therapy in a naturalistic setting in contrast to the optimised conditions of a clinical trial. Our findings indicate that Tubulcus was efficacious, well tolerated and positively accepted by patients with venous leg ulcers. Efficacy of compressive therapy was demonstrated in actively controlled studies. However, with the knowledge that poor patients compliance is one of the main problems of treating ulcers with compressive therapy in daily practice, a large-scale observeillance study like the one reported here gives interesting additional information about effectiveness and tolerance of compressive therapies (16). The efficacy of Tubulcus was investigated before in a randomised controlled study in comparison with a short-stretch bandage, showing a complete healing rate of about 60% in both groups after a mean time scale of treatment of 42 days in a highly selected population of ulcer patients (inclusion criteria: largest diameter of the ulcer <5 cm, duration of ulcer less than 3 months, treatment only by physicians or medical staff) (7). Within the given observation period of three months and considering so-called real life conditions in this PMOS with the treatment of any patient who required compressive therapy, its efficacy results are favourable for the Tubulcus therapy. Though the rate of complete healings was lower, in total more than two thirds of all patients took a benefit from the compressive therapy with the Tubulcus. The clinical condition of the ulcer of other patients was ameliorated though without decrease of the ulcer size. Only in two patients, the ulcer worsened. Strong support is given to the favourable responder rate by a significant reduction of oedema which is a prerequisite for healing of ulcer (14, 17, 20) but also with the global ratings of efficacy by physicians and patients, which were good or very good for the great majority of treatments performed. These results are promising when taking into account that further healing can be expected at least for those patients who improved already during the observation period (10). As much as about two thirds of patients who continued Tubulcus treatment after this period might represent candidates for complete healing after a sufficiently long treatment. This was already shown in another mono-centre observational study with Tubulcus over six months in 53 patients with long-lasting (average: 1 year) ulcers (9). Complete healing succeeded in 69.8% of the patients, of whom 35% achieved complete healing only after three months. A longer observation period should therefore be considered in further studies. No differences were detected in subgroup analyses (data not reported) with stratifications of the patient population according to gender or primary origin of the ulcer (post-thrombotic venous insuffi-

5 16/28 Vanscheidt, Kohnen, Achhammer ciency versus varicosis, CVI and others). Therefore, the Tubulcus treatment proved as qualified for all ulcer patients. It was up to the physicians, depending on the clinical status of the ulcer and the need for local treatment of the wounds to decide on the frequency of changes of Tubulcus and whether or not the Tubulcus should also be worn at night. The findings show a broad range between daily changes, changes every second day or twice a week until ending in weekly changes. Generally, the frequency of changes decreased during the course of treatment. This indicates that Tubulcus may very well be placed for several days and especially also over night. The comfort for the patient is a very important factor to increase compliance. The questionnaire used in and developed for this study aimed at learning more about eventual problems of patients. We found that the patients experiences in this study in wearing Tubulcus (daily hygiene, slipping, appearance, general convenience), was judged to be good or very good by most of them. Conclusion The application of the correct and digressive pressure, which is required to treat ulcers effectively, is hardly achieved with bandages.their application must be trained thoroughly and probably is never achieved when the patient or a member of his family applies the bandages in daily practice. The ready-made medical compression device Tubulcus exerts the appropriate pressure independently of the fitter.applying Tubulcus by the patients or family members is performed without major problems and well accepted. Treatment with Tubulcus is efficacious and safe. The time required for treatment may exceed three months in every second patient. With a well-designed effective compression device like Tubulcus and a better comfort, compliance problems might be reduced and healing rates increased in daily practice. References 1. Cornwall JV, Dore CJ, Lewis JD. Leg ulcers: epidemiology and aetiology. Br J Surg 1986; 73: Fletcher A, Cullum N, Sheldon TA. A systemic review of compression treatment for venous leg ulcers. Br Med J 1997; 315: Gallenkemper G, Bulling BJ, Kahle B, Klüken N, Lehnert W, Rabe E, Schwahn-Schreiber Chr. Leitlinien zur Diagnostik und Therapie des Ulcus cruris venosum. Phlebologie 2000; 4: Gardon-Mollard C. Tubular compression in the treatment of venous ulcers of the leg: a new graduated tubular device. Phlebology 2000; 15: Häfner HM, Götzke N, Kohnen R, Jünger M. Anpressdruck eines zirkulären Fertigverbandes im Vergleich zu phlebologischen Kompressionsverbänden. Der Hautarzt 2001; 52: Häfner HM, Eichner M. Klinische Überprüfung des Anpressdruckes unterschiedlicher Konfektionsgrössen des zirkulären Kompressionsverbandes Tubulcus. Phlebologie 2002; 5: Häfner HM, Hartmann M, Jünger M. Ein Fertigverband zur Kompressionstherapie des ulcus cruris venosum in der klinischen Erprobung: Vasomed 2001; 6: Herzig R, Florek HJ. Befundadaptierte chirurgische Behandlung des therapieresistenten Ulcus cruris venosum. Phlebologie 2002; 3: Hübner K. Results of an open long-term observational study of leg ulcer therapy with Tubulcus. Phlebology Digest 2003; 16: Kantor J, Margolis DJ. A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks. Br J Dermatol 2000; 142: Mayberry JC, Moneta GL, Taylor LM, Porter J. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery 1991; 109: Nelson EA, Barbenel JC, Ruckley CV, Queen D. The effect of training using feedback from a pressure monitor on nurses bandaging techniques. In: Raymond-Martimbaud P, Prescott R, Zummo M (eds). Phlébologie 92. Paris: John Libbey Eurotext 1992: Nelzen O, Bergqvist D, Lindhagen A. Venous and non-venous leg ulcers: clinical history and appearance in a population study. Br J Surg 1994; 81: NHS Centre for Reviews and Dissemination. Compression therapy for venous leg ulcers. Effective Health Care 1997; 3: Pirk O. Chronische Wunden: Viel Geld für nichts? Dtsch Ärztebl 2000; 45: Palfreyman SJ, Lochiel R, Michaels JA. A systemic review of compression therapy for venous leg ulcers. Vasc Med 1998; 3: Prasad A, Ali-Khan A, Mortimer P. Leg ulcers and oedema: a study exploring the prevalence, aetiology and possible significance of oedema in venous ulcers. Phlebology 1990; 5: Rabe E, Pannier-Fischer F, Bromen K, Schuldt K, Stang A, Poncar CH,Wittenhorst M, Bock E, Weber S, Jöckel KH. Bonner Venenstudie der Deutschen Gesellschaft für Phlebologie. Epidemiologische Untersuchung zur Frage der Häufigkeit und Ausprägung von chronischen Venenkrankheiten in der städtischen und ländlichen Wohnbevölkerung. Phlebologie 2003; 32: Ruckley CV. Socioeconomic impact of chronic venous insufficiency and leg ulcers. Angiology 1997; 48: Salaman RA. The aetiology and healing rates of chronic venous ulcers. J Wound Care 1995; 4: Correspondence to: Prof. Dr. med. Wolfgang Vanscheidt Paula-Modersohn-Platz Freiburg