European Urology 48 (2005)

Transcription

1 European Urology European Urology 48 (2005) Intermittent Catheterisation with Hydrophilic-Coated Catheters (SpeediCath) Reduces the Risk of Clinical UrinaryTract Infection in Spinal Cord Injured Patients: A Prospective Randomised Parallel ComparativeTrial D.J.M.K. De Ridder a, *, K. Everaert b, L. García Fernández c, J.V. Forner Valero d, A. Borau Durán e, M.L. Jauregui Abrisqueta f, M.G. Ventura g, A. Rodriguez Sotillo h a Department of Urology, University Hospitals KU Leuven, Herestraat 49, 3000 Leuven, Belgium b University of Ghent, Belgium c Spinal Cord Injury Unit, Hospital Vall d Hebron, Barcelona, Spain d Hospital La Fé, Valencia, Spain e Fundacio Institut Guttmann, Barcelona, Spain f Hospital de Cruces, Cruces Baracaldo- Vizcaja, Spain g Centre de Traumatologie et Révalidation, Brussels, Belgium h Spinal Cord Injury Unit, Hospital Juan Canalejo Maritimo de Oza, La Coruña, Spain Accepted 26 July 2005 Available online 15 August 2005 Abstract Objectives: To compare the performance of SpeediCath hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters, in traumatic spinal cord injured patients presenting with functional neurogenic bladdersphincter disorders. Methods: A 1-year, prospective, open, parallel, comparative, randomised, multi centre study included 123 male patients, 16 y and injured within the last 6 months. Primary endpoints were occurrence of symptomatic urinary tract infection (UTI) and hematuria. Secondary endpoints were development of urethral strictures and convenience of use. The main hypothesis was that coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria. Results: 57 out of 123 patients completed the 12-month study. Fewer patients using the SpeediCath hydrophiliccoated catheter (64%) experienced 1 or more UTIs compared to the uncoated PVC catheter group (82%) (p = 0.02). Thus, twice as many patients in the SpeediCath group were free of UTI. There was no significant difference in the number of patients experiencing bleeding episodes (38/55 SpeediCath; 32/59 PVC) and no overall difference in the occurrence of hematuria, leukocyturia and bacteriuria. Conclusions: The results indicate that there is a beneficial effect regarding UTI when using hydrophilic-coated catheters. # 2005 Elsevier B.V. All rights reserved. Keywords: Neurogenic bladder; Intermittent catheterisation; Spinal cord injury; Urinary tract infection; Catheterrelated infection 1. Introduction * Corresponding author. Tel ; Fax: address: Dirk.deridder@uz.kuleuven.ac.be (D.J.M.K. De Ridder). Intermittent catheterisation is the gold standard in management of neurogenic bladder emptying disorders. In spinal cord diseased or injured people, /$ see front matter # 2005 Elsevier B.V. All rights reserved. doi: /j.eururo

2 992 D.J.M.K. De Ridder et al. / European Urology 48 (2005) intermittent catheterisation has been life saving by reducing the risk of upper urinary tract deterioration and urosepsis [4]. The original sterile technique was time consuming and costly. The introduction of clean intermittent catheterisation (CIC) by Lapides has changed the management of bladder emptying disorders dramatically. In his view, the key to avoiding urinary tract infections (UTI) is avoidance of high intravesical pressure and over-distension of the bladder, thus preserving an adequate blood supply to the bladder wall [7]. Long-term clean intermittent self-catheterisation is safe and well accepted. Good support and professional instruction on the catheterisation are necessary to obtain and maintain patient compliance. However, an early dropout rate of about 20% has been described in children and adolescents [9]. Patients usually stop CIC because bladder function recovers, because of persistent incontinence, deterioration of the neurological disease or occurrence of an urethral false passage [10]. In an attempt to reduce catheter-associated bacteriuria and urethritis, hydrophilic-coated catheters have been introduced to the market in addition to the classic uncoated polyvinyl chloride (PVC) catheters. In a recent review, Hedlund et al. stated with clinical evidence that hydrophilic catheters provide decreased urethral irritation and better patient satisfaction. It is suggested that the use of hydrophilic catheters might lead to a decrease in both bacteriuria and longterm urethral complications. However, there is a lack of well designed randomised trials comparing the performance of hydrophilic coated and uncoated catheters [5]. For this paper a prospective, open, parallel, comparative, randomised, multi-centre trial was designed to test the hypothesis that hydrophilic-coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria. The aim of the study was to compare the performance of SpeediCath hydrophiliccoated catheters and manually lubricated uncoated PVC catheters in traumatic spinal cord injured patients. 2. Material and methods Only male spinal cord injured patients, who were 16 or more years old and had been injured less than 6 months were included. Included patients presented with neurogenic bladder emptying disorders, needing intermittent catheterisation at least 3 times a day. Patients with symptomatic UTI and patients with urethral stenosis or fibrosis were excluded, as were mentally unstable patients and those participating in another clinical trial. Eight centres participated (5 in Spain, 3 in Belgium). After inclusion in the study and the initial study visit, visits were scheduled at day 15 and subsequently at month 1, 2, 3, 6, 9 and 12. During the course of the trial, patients who received prophylactic antiseptic or antibiotic treatment were excluded as well as those in whom a permanent catheter was used for a period of more than 10 days. The study was approved by the appropriate local ethical committees. Patients were randomised in two groups. One group used the hydrophilic-coated SpeediCath 1 catheter (Coloplast). This readyto-use catheter for single use is made of polyurethane with a hydrophilic coating consisting primarily of polyvinyl-pyrrolidone. The second group used uncoated PVC catheters (Conveen, Coloplast), which were lubricated manually with a water-soluble lubricant gel, containing no active ingredients and delivered in 5 g sachets (Aquagel Lubricating Jelly, Adams Healthcare Ecolab). Both catheters were available for the study in size Ch 10, Ch 12 and Ch 14. The primary study parameters were occurrence of symptomatic UTI and occurrence of hematuria. In this study, UTI was defined as a clinical infection with symptoms of UTI and for which treatment was prescribed. Secondary parameters were development of strictures and convenience of use. At each visit, data from the patient s logbook were collected regarding the occurrence of bleeding episodes since the last visit, as well as UTI symptoms experienced and details about antibiotic treatment. At each visit microbiologic and cytologic examinations of a urine sample were performed to assess bacteriuria, leukocyturia and hematuria. Subjective assessment of catheter introduction, withdrawal, time spent and the satisfaction with the catheter was done after 6 and 12 months using a 4-point scale. The sample size calculation was based on values obtained from the article of Bakke et al. [1]. A sample size of 50 in each group would provide a 90% power to detect difference between the groups using a two-group t-test with a 0.05 one-sided significance level. To compensate for nonevaluable patients, it was planned to include 60 patients in each group. Patients were randomised in blocks of 4 using a randomisation list produced automatically using Medstat software version 2.1. The randomisation was performed by the investigator using sealed coded envelopes provided by the study sponsor and containing the identity of the assigned treatment. The data were analysed using t-test, Chi-square and Wilcoxon two-sample tests where appropriate. 3. Results In total 123 male spinal cord injured patients were randomised, 62 to the PVC group, 61 to the SpeediCath group. Patients were included from January 2001 to June There were no significant differences in the demographics and baseline characteristics between the groups. The mean age was y in the PVC group and y in the SpeediCath group. The ASIA levels of both groups on day 1 are listed in Table 1. During the period before inclusion in the trial different bladder emptying methods were used. These are listed in Table 2. Of the 123 patients included in the study only 57 patients completed the study (Fig. 1). The main reasons for the high dropout rate were restored urinary function and thus no further need for catheterisation, change of

3 D.J.M.K. De Ridder et al. / European Urology 48 (2005) Table 1 The distribution of patients (n = 122) at inclusion using the ASIA impairment scale A Complete 43 (69) 36 (60) B Incomplete 4 (6) 8 (13) C Incomplete 7 (11) 11 (18) D Incomplete 8 (13) 5 (8) E Normal 0 (0) 0 (0) Table 3 The number of patients free of UTI and experiencing 1 or more UTIs during the study period 0 UTI n (%) 1 UTI n (%) PVC 11 (18) 51 (82) SpeediCath 22 (36) 39 (64) The difference between the two groups is statistically significant (p = 0.02, chi-square). Table 2 Distribution of patients (n = 123) into bladder management groups before inclusion in the trial Urethral indwelling catheter 58 (94) 58 (95) Suprapubic catheter 7 (11) 4 (7) Intermittent catheterisation 17 (27) 20 (33) Condom catheter, penile sheath 1 (2) 1 (2) Abdominal or manual effort 0 (0) 0 (0) Percussion 0 (0) 1 (2) bladder management to an indwelling catheter and withdrawal of consent. One of the primary parameters in this study was to investigate the occurrence of UTIs in the two catheter groups. The number of patients free of UTI during the study period and the number of patients experiencing 1 or more UTIs are shown for the two groups in Table 3. The results show that fewer patients using the SpeediCath catheter experienced 1 or more UTIs compared to the PVC group (p = 0.02, chi-square). Thus, twice as many patients in the SpeediCath group were free of UTI during the study period of one year. Furthermore, the median number of UTIs per 1000 catheter days in the SpeediCath group was lower (5.4, n = 61), but not significantly, compared to the PVC group (8.1, n = 61). For both groups the incidence of UTIs per 1000 catheter days was markedly decreased after the patients were discharged from hospital. There was no significant difference in the mean number of catheterisations in the two groups during the course of the study. At the end of the study, the mean number of catheterisations per day was 3.6 for the PVC group and 3.4 for the SpeediCath group. The primary safety endpoint in this study was the occurrence of bleeding episodes in the two catheter groups. There was no significant difference in the median or number of patients experiencing bleeding episodes (38/55 SpeediCath; 32/59 PVC). For both Fig. 1. Flow of participants. AE: adverse event, PV: protocol violation, WC: withdrawal of consent, LF: lost to follow-up,?: information missing, D: death.

4 994 D.J.M.K. De Ridder et al. / European Urology 48 (2005) Table 4 The number and percentage of patients/helpers who were very satisfied with the catheter after 6 and 12 months catheters, the mean number of bleeding episodes per 1000 catheterisations was shown to decrease over time, most dramatically during the first days of the study. The laboratory examination of urine samples collected at every study visit showed no significant differences in the occurrence of bacteriuria, leukocyturia and hematuria between the two groups, except at the initial study visit, where a higher number of patients had microscopic hematuria (p = 0.02) and bacteriuria (p = 0.03) in the SpeediCath group compared to the PVC group. This difference was eliminated at day 15. The secondary parameters were development of strictures and convenience of use in the two groups. One incidence of stenosis occurred in a patient from the PVC group during the study period. Overall satisfaction with the catheter used was similar in both groups. Nevertheless, more patients in the SpeediCath group were very satisfied after 6 months compared to patients in the PVC group (Table 4). Although there was no significant difference, more patients/care providers in the SpeediCath group found the overall catheterisation procedure, the introduction and withdrawal of the catheter very easy or easy compared to the PVC group. The time needed to perform the catheterisations was similar in both groups. 4. Discussion 6 months 6 (15.4) 10 (33.0) 12 months 7 (21.9) 9 (36.0) The observed difference is not statistically significant. In many centres catheters for intermittent catheterisation are being reused. Single-use catheters are usually used when reimbursement can be provided. Reusing the same catheter seems to lead to a higher infection rate and an increase in stiffness of the catheter material [2,6]. According to some authors, good education and training, clean and atraumatic technique are the most important parameters to assure long-term success of CIC. Choice of type of catheter and of catheterisation technique are to be adapted to the patient s individual anatomic, social and economic state [12]. In spinal cord injury literature UTIs are still not clearly defined [8]. This is partially reflected in the apparently conflicting results between the effect on bacteriuria and on clinical UTI. In clinical practice however the reduction in the number of clinical UTI is the most important issue. In this study it was found that the number of spinal cord injured patients free of clinical UTI was doubled in the SpeediCath group compared to the PVC group over a one-year period. This indicates that there is a beneficial effect regarding UTI when using hydrophilic-coated catheters, primarily in patients with fewer randomly occurring UTIs. The beneficial effect of using a hydrophilic-coated catheter with respect to UTI may be more pronounced than shown in this study, if patients change from reusing manually lubricated PVC catheters to readyto-use hydrophilic-coated catheters for single use. When damage to the urethra occurs, the mucosal barrier towards infections is compromised. Indicators of urethral damage such as occurrence of macroscopic hematuria and leukocyturia would therefore be expected to correlate with occurrence of infection. However, this appears not to be the case. There was no significant difference in leukocyturia or in the number of patients experiencing bleeding episodes between the two groups. At the initiation visit the Speedicath group had significantly higher leukocyturia and hematuria, but despite the intermittent catheterisation these numbers were no longer significantly different from the PVC group at day 15. Thus, other factors than urethral damage appear to play a role in development of UTI. It has been shown that innate host defence mechanisms or genetic factors can influence the susceptibility to UTI [11]. Besides these, the frequency of catheterisation might influence the occurrence of symptomatic bacteriuria by increasing the time that colonised urine resides in the bladder (in case of infrequent catheterisation) or by increasing the risk of urethral damage (too frequent catheterisation). Volume-dependent instead of time-dependent intermittent catheterisation has proven to reduce the number of infections as well [3]. The number of patients who completed the study was only 57 (46%). The dropout rate was much higher than expected, but may be explained in part by the study design. In an attempt to minimise previous experience with intermittent catheterisation, it was decided to include only patients injured within the last 6 months. These patients were still hospitalised at inclusion, and were not fully stabilised following injury. Therefore, a large number of patients either recovered their bladder function during the study or their condition deteriorated so that further operations

5 D.J.M.K. De Ridder et al. / European Urology 48 (2005) were needed and bladder management was changed to a permanent catheter. The number of dropouts and the reason why is comparable in both groups. Limiting the inclusion to only complete spinal cord lesions would have made this study nearly impossible since the number of this type of patients is too low, even in 8 centres. 5. Conclusion In this study the performance of SpeediCath hydrophilic-coated catheters was compared with the performance of uncoated PVC catheters. The main hypothesis was that coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria. Significantly fewer patients using the SpeediCath hydrophilic-coated catheter experienced clinical UTIs compared to the uncoated PVC catheter group. Thus, twice as many patients in the SpeediCath group were free of clinical UTI during the 1-year study period. These findings could have an important impact on the quality of life of the patients. There was no significant difference in the number of patients experiencing macroscopic bleeding episodes and no overall difference in the occurrence of hematuria, leukocyturia and bacteriuria. The results indicate that there is a beneficial effect regarding clinical UTI when using hydrophilic-coated catheters. Acknowledgment The authors wish to thank all the contributors to this study from the eight centres involved. References [1] Bakke A, Vollset SE, Hoisaetter PA, Irgens LM. Physical complications in patients treated with clean intermittent catheterisation. Scand J Urol Nephrol 1993;27: [2] Bogaert GA, Goeman L, De Ridder D, Wevers M, Ivens J, Schuermans A. The physical and antimicrobial effects of microwave heating and alcohol immersion on catheters that are reused for clean intermittent catheterisation. Eur Urol 2004;46: [3] DeRidder D, VanPoppel H, Baert L, Binard J. From time dependent intermittent selfcatheterisation to volume dependent selfcatheterisation in Multiple Sclerosis using the PCI 5000 Bladdermanager(R). Spinal Cord 1997;35(9): [4] Guttman L, Frankel H. The value of intermittent catheterisation in the early management of traumatic paraplegia and tertraplegia. Paraplegia 1966;4: [5] Hedlund H, Hjelmas K, Jonsson O, Klarskow P, Talja M. Hydrophilic versus non-coated catheters for intermittent catheterization. Scand J Urol Nephrol 2001;35: [6] Kovindha A, Mai WNC, Madersbacher H. Reused silicone catheter for clean intermittent catheterization (CIC): is it safe for spinal cordinjured (SCI) men? Spinal Cord 2004;42(11): [7] Lapides J, Diokno AC, Silber SM, Lowe BS. Clean, intermittent selfcatheterization in the treatment of urinary tract disease. J Urol 1972;107: [8] Liss PE, Aspevall O, Karlssson D, Forsum U. Terms used to describe urinary tract infections - the importance of conceptual clarification. APMIS 2003;111(2): [9] Pohl HG, Bauer SB, Borer JG, et al. The outcome of voiding dysfunction managed with clean intermittent catheterization in neurologically and anatomically normal children. Bju Int 2002;89(9): [10] Webb RJ, Lawson Auriol L, Neal DE. Clean intermittent self-catheterisation in 172 adults. Br J Urol 1990;65:20 3. [11] Wullt B, Bergsten G, Fischer H, et al. The host response to urinary tract infection. Inf Dis Clin North Am 2003;17(2): [12] Wyndaele J. Intermittent catheterization: which is the optimal technique? Spinal Cord 2002;40(9):432 7.