Multi-Centre Study of Intraurethral Valve-Pump Catheter in Women with a Hypocontractile or Acontractile Bladder

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1 European Urology European Urology 48 (2005) Female Urology ^ Incontinence Multi-Centre Study of Intraurethral Valve-Pump Catheter in Women with a Hypocontractile or Acontractile Bladder T.Y.-H. Chen a, *, Y. Ponsot a, M. Carmel a, N. Bouffard a, M.J. Kennelly b, L.M. Tu a a Department of Urology, Sherbrooke University Hospital Centre, th Avenue Nord, Fleurimont, PQ J1H 5N4, Canada b Carolinas Medical Centre, Charlotte, NC, USA Accepted 22 April 2005 Available online 23 May 2005 Abstract Objectives: To compare the safety, effectiveness and patient satisfaction of an intraurethral valve-pump catheter (In- Flow TM ) versus the current standard of care, clean intermittent catheterization (CIC), for females with hypocontractile or acontractile bladder. Materials and methods: The study was a multi-centre, prospective, single-arm crossover study. Eligible patients underwent a 1-week In-Flow tolerability trial. Successful patients then continued through an 8-week baseline phase using CIC, followed by a 16-week In-Flow treatment phase, and a final 4-week treatment withdrawal phase. Outcome measures included post-void residual (PVR), Wagner incontinence-specific quality of life (I-QOL), rate of urinary tract infection and adverse events. At study completion, open enrolment was offered. Results: A total of 273 women with a mean age of 48.9 years using CIC entered the study in 18 centres under either the original (n = 88) or revised protocols (n = 185). The revised protocol included the addition of a 1-week tolerability trial. The reasons for the large early withdrawal of subjects (169/273) were mainly related to initial discomfort and leakage. A total of 77 patients completed the In-Flow treatment phase. PVR was comparable during baseline CIC phase and In-Flow treatment phase (20.3 ml vs ml), with significantly improved quality of life (QOL; mean improvement of I-QOL score +25.9; p < 0.001). Conclusion: The In-Flow catheter appears to be a viable alternative to CIC. A subgroup of patients, mainly those unsatisfied with the currently available treatments, was more likely to tolerate In-Flow catheters, and they may achieve enhanced independence and QOL. # 2005 Elsevier B.V. All rights reserved. Keywords: Hypocontractile bladder; Acontractile bladder; Quality of life 1. Introduction A hypocontractile or acontractile bladder is a debilitating condition with few satisfactory therapeutic options. Clean intermittent catheterization (CIC), first proposed by Lapides et al. [1], remains the most popular alternative to the indwelling catheter in these patients. Although safe, it is still associated with rare complications, such as urethral false passages * Corresponding author. Tel x14595; Fax: address: tony.chen@mail.mcgill.ca (T.Y.-H. Chen). and bladder perforation [2]. Additionally, CIC provides a particular challenge for certain groups of patients, particularly the elderly, visually impaired, mentally handicapped, and those with limited manual dexterity. A new treatment modality, an intraurethral valvepump catheter (In-Flow TM ; Fig. 1), has been designed to assist women seeking an alternative to CIC. The In- Flow device (SRS Medical, N. Billerica, MA, USA) is designed for temporary (<29 days) use and is comprised of a short silicone catheter containing an internal valve and pump mechanism operated by an external remote control unit. The silicone catheter is produced /$ see front matter # 2005 Elsevier B.V. All rights reserved. doi: /j.eururo

2 T.Y.-H. Chen et al. / European Urology 48 (2005) Fig. 1. The In-Flow device. in lengths ranging from 3 to 7 cm (in 0.5 cm increments) and in 2 diameters: 24 and 28 Fr. The appropriate length is determined by measuring the urethral length using a graduated Foley catheter. A disposable inserter is used to introduce the device into the urethra (Fig. 2a). The device is fixed in position by flexible silicone fins that open like flower petals at 629 the level of the bladder neck (Fig. 2b) and by a flexible flange at the external urethral meatus (Fig. 2c). The device is routinely replaced every 29 days by the caregiver or patient. It is easily removed by pulling or manipulating the external flange that collapses the fixation system (Fig. 3a c). Neither method causes damage to the bladder or urethra due to the flexibility of the silicone. In the core of the valve and pump mechanism is a small magnet, which is remotely energised by the InFlow activator (Fig. 4). To operate the mechanism, the activator is held at the pubic area and the on button is depressed. The valve then opens and the miniature rotor spins at a speed of 10,000 rpm, generating a urine flow of ml/s. When the on button is released, the activator beeps and its magnet automatically counter-spins in order to close the valve and restore continence. The activator is powered by two 3 V lithium batteries that are replaced every 4 6 weeks. Previous studies have examined the use of this device in female patients with mixed results [3 6]. To date, there has been no published study comparing the InFlow catheter with any other treatment modality. This study aims to evaluate the safety and effectiveness of the In-Flow catheter in females with a hypocontractile Fig. 2. Application of In-Flow catheter. Fig. 3. Removal of In-Flow catheter.

3 630 T.Y.-H. Chen et al. / European Urology 48 (2005) to better identify patients who would complete the study by including a 1-week In-Flow tolerability trial. Patients who successfully demonstrated tolerance to the device then continued through the rest of the protocol. The primary study endpoint was evaluating the changes in the post-void residual (PVR). A secondary efficacy endpoint was assessing the improvement in the Wagner scale [7]. Safety was evaluated by comparing the rate of adverse events between the baseline CIC phase and the In-Flow treatment phase. In order to identify the patients most likely to tolerate and therefore benefit from In-Flow catheter, elements of the subjects baseline characteristics and medical history were studied. Statistical analysis of the outcome measures was performed with the t-test or x 2 where appropriate. 3. Results Fig. 4. In-Flow activator (remote control) with protective cover (left) and without protective cover (right). or acontractile bladder, by comparing this device with the current standard of care, CIC. 2. Materials and methods The study was a multi-centre, single-arm, crossover design. The study was initially sponsored by Influence Inc. and then was acquired by American Medical Systems, Inc. (AMS). Patient recruitment started in June 1997 after obtaining approval from ethics committees at each individual site, and patients were followed until March 2000 when AMS terminated the study for unrelated business reasons just prior to their initial public offering. Patients were first evaluated with urodynamic evaluation, cystoscopy, urinalysis and urine culture and were asked to complete the Wagner I-QOL questionnaire [7]. Eligible patients were female patients with hypocontractile or acontractile bladder without contraindication to having medical magnetic device or other concurrent conditions of the lower urinary tract. In the original protocol, eligible patients went through an 8-week baseline phase using CIC, 16-week In-Flow treatment phase, and a final 4-week treatment withdrawal phase. At study completion, open enrolment was offered. The protocol was revised in December of 1997 in order A total of 273 women were enrolled in a study from 18 centers. The mean age of the study population was years, which was similar for completers and non-completers (49.0 vs. 52.3, p = 0.15). The mean duration of CIC was months (range ) and was similar for completers and noncompleters (68.0 month vs months, p = 0.96). A detailed breakdown of patient participation at each stage is summarised in Table 1. Out of 273 patients, a total of 77 patients completed the study, and 60 of them opted for post-treatment open enrolment. Among the completers, the aetiology of hypocontractile or acontractile bladder included psychiatric or idiopathic disorders (38.2%), spinal disease or injury (34.2%), multiple sclerosis (25%), spina bifida (18.4%), paralysis of some extent (17.1%), and other causes (30%). As some patients have more than one cause for voiding dysfunction, the total exceeds 100%. The reasons for withdrawal are detailed in Table 2. The most frequently reported reason for withdrawal was discomfort, followed by leakage, although it would appear to some extent to be a continuation of their baseline incontinence, since 42% of all patients reported incontinence as a pre-existing condition. Table 1 Patient flow diagram Visit Original protocol Revised protocol Screening and baseline Entered study Withdrawal Remaining Withdrawal Remaining Tolerability trial N/a Baseline Withdrawn prior to completing screening/baseline Active treatment Entered active treatment Completed active treatment Withdrawn prior to completing active treatment Post-treatment open enrolment 23 37

4 T.Y.-H. Chen et al. / European Urology 48 (2005) Table 2 Reasons for withdrawal Reason for withdrawal Baseline, Active screening a treatment b (n = 115) (n = 81) Freq a % Freq b % Subject request Non-compliance Concurrent illness Complication Leakage Discomfort Frequency/urgency Other complications Adverse experience Death Other Sponsor closed study a One hundred and fyfteen subjects withdrew during baseline and screening; frequencies do not total 115 because of multiple reasons for withdrawal. b Eighty one subjects withdrew during active treatment; frequencies do not total 81 because of multiple reasons for withdrawal. The mean PVR was comparable between the baseline CIC and treatment phases among the completers (20.3 ml 24.4 vs ml 15.2, p = NS). Information regarding quality of life (QOL) was available for 66 patients by week 16 of the treatment phase. There was a significant improvement in I-QOL scores after treatment, with a mean increase of I-QOL score , over the baseline ( p < , one-sample t-test). Due to the varying lengths of exposure to the study device, adverse event data are presented in the number of events per person-month of exposure and the percentage of patients experiencing the adverse events (Table 3). Among the completers, the number of urinary tract infection per person-month decreased slightly from Baseline to Treatment phase ( ). It should be noted that the rate of asymptomatic bacteriuria detection may be artificially elevated due to investigative requirements. During the Treatment phase, a urine sample was sent for culture even with unscheduled visits for unrelated complaints. As a result, there were many more urine samples obtained and examined compared to the Baseline phase. An attempt to identify the characteristics of the patients most likely to benefit from the catheter was made; however, neither this study nor the four previously published studies have identified any reliable predictors of treatment success based on either patient demographics or diagnosis of primary disease [3 6] (Table 4). We did note, however, that completers are more likely to have a lower baseline I-QOL score, more impairment in ambulation and manual dexterity, more likely to use an adult diaper, less likely to have undergone prior urogenital surgery, or suffer from urinary retention. 4. Discussion Several strategies to enhance voiding in the hypocontractile or acontractile bladder have been explored; however, CIC has remained the most popular and effective treatment for this condition [1,8]. Nevertheless, this treatment is not suited to all patients. For instance, most elderly patients chose indwelling catheterization despite its recognised dangers, instead of CIC [9]. As one of the few alternatives to CIC and because of its novel technology, the In-Flow catheter has become the subject of a number of publications. Madjar et al. [3] have described their initial and long-term experience with 92 patients. They reported high early and late withdrawal rates that were similar to those in our study. They also found that for patients able to tolerate the In- Flow catheter, there were very high levels of satisfaction and no significant complications. Schurch et al. [4] evaluated device use in 18 patients, observed a high Table 3 Adverse events encountered by the completers Exposure time (person-month) Pre-existing Baseline screening Device screening Baseline Treatment Post treatment (N/a) (17.5) (11.6) (175.4) (263.9) (444.7) % pts X/pt-mo. % pts X/pt-mo. % pts X/pt-mo. % pts X/pt-mo. % pts X/pt-mo. % pts X/pt-mo. Incontinence Urethral discomfort Asymptomatic bacteriuria Frequency/urgency spasm UTI Expulsion Haematuria

5 632 T.Y.-H. Chen et al. / European Urology 48 (2005) Table 4 Completers vs. non-completers Baseline characteristic Non-completer Completer p Value (t-test) Mean SD Mean SD Duration of CIC (months) a Age (years) b IQOL a, 0.04 b Medical history freq/n % freq/n % p value (x 2 ) Urolithiasis 61/ / Neoplastic disease 62/ / Inflammatory processes 60/ / Surgically sterile post menopausal 23/ / Limited ability to fully ambulate 22/ / <0.01 Limited manual dexterity 42/ / Caregiver required for activities 48/ / Urinary incontinence 14/ / Urinary retention 9/ / Urogenital surgery 40/ / <0.01 Baseline practice Pad use 30/ / Adult diaper 46/ / <0.01 Pharmacologics for incontinence 43/ / a t-test with unequal variance estimate. b t-test with equal variance estimate. initial drop-out rate (66%), primarily due to discomfort and leakage, and concluded that, although it may be useful for short periods, the device is unsuitable for long-term use. Interestingly, their clinical results, in terms of adverse events, are very similar to those of Madjar et al. [3], despite the differences in conclusions between these two studies. The most convincing evidence to date for use of the In-Flow catheter can be found in a recently published Australian study of 20 patients, which reported high satisfaction levels and QOL improvement among a selected group of patients [6]. Lynch et al. [6] reported an I-QOL improvement of 54.6 (84%) after 12 months. Seven (7) patients withdrew from the study (35%), although most for reasons unrelated to device use. (One died, one developed an unrelated medical condition that precluded device use, and three reportedly regained normal bladder function.) Even considering the clinical issues noted, the In- Flow catheter appears to be a worthwhile addition to current treatment modalities. It is clearly not suitable for all female patients with a hypocontractile or acontractile bladder; however, it is a highly satisfactory alternative to a subgroup of patients for whom CIC proves challenging. It is no coincidence that the patients who are more likely to tolerate the device in our study have lower voiding-related QOL, greater dependence on adult diapers, and are more handicapped in terms of ambulation and manual dexterity. For these patients, In-Flow catheter gives them increased independence and improves their voiding-related QOL, things no other treatment can provide. In our study, the I-QOL improved at an average of It was found that an increase in 17 points of I-QOL score corresponds to very much better in terms of patients global perception of change [10]. Although the population is different from our group, the magnitude of change of the I-QOL score in our study certainly reflects clinically significant improvement. The In-Flow catheter is not only a relatively new device, it is a new type of device and we are still learning about its properties. Certainly, we gained some valuable experience during the course of our study. Although, in general, it is not easy to get used to having a foreign body in the urethra, we learned that specific causes of complaint can often be simply rectified: (a) Unnecessary procedures involving instrumentation of the urethra should be avoided prior to immediate insertion of this device to optimize chances of patient s acceptance. (b) Patients must have adequate support from medical and paramedical teams, especially during the initial device-fitting phase. In general, our experience was that such support was required only through the first few weeks of In-Flow use. Once acclimatized to the presence of the device, discomfort and even episodes of unexpected leakage tended to subside in those patients who continued to use the device.

6 T.Y.-H. Chen et al. / European Urology 48 (2005) (c) Optimal catheter sizing is essential for compliance. There are currently 2 available diameters, 24 and 28 Fr and 9 lengths (5 9 cm, in 0.5 cm increments). It may take several fittings to get the right size, i.e., comfortable and well fitted. (d) The position of the petals or fins used to secure the device at the bladder neck may also influence tolerability. Post study, we occasionally resorted to cutting off one or more of these fins to improve acceptance. Care should be taken, as it can compromise catheter fixation and cause the device to be expelled unexpectedly. Alternatively, gentle rotation of the device in situ to move the external flange of the catheter from the recommended vertical (12 O clock) to a horizontal (3 O clock) position may assist in removing pressure and increasing patient comfort. To date, there have been no reports of urethral dilatation as a result of long-term In-Flow usage. Given the relatively short treatment time, observable tissue damage was not expected in our study and, in fact, was not found. We have continued to follow 15 patients for over 4 years, and even in this group annual cystoscopy has revealed no abnormality in the bladder or urethra of any patient, even if wheelchair driven. This is consistent with the findings of other longer term studies, none of which have documented evidence of patulous urethra on cystoscopic examination. Indeed, Patrick et al. [10] reported that not only was no development of patulous urethra seen in the 20 patients who used the In-Flow device for more than 12 months, but that beneficial tissue changes occurred. Two patients who had begun to develop a patulous urethra as a result of long-term catheterization prior to entering their study appeared to resolve this complication after 2 months of use of the device. The authors speculated that the main stimulus for the formation of a patulous urethra might be the relatively constant pressure of the balloon of the Foley catheter on the bladder neck rather than the dilatation of the urethra itself. In comparison to the anchoring of a Foley catheter at the bladder neck, the six narrow petals or fins that maintain the In-Flow device internally might exert little or no pressure on the internal urethra. In wheelchair driven patients, the pressure is mostly absorbed by the ischium. Hence little pressure, if at all, is directly applied against the urethra. There is therefore no danger of erosion in these patients. Longer term follow-up should be continued in order to assess this theory. Cystometrogram may also need to be periodically administered to ensure that patients do not develop decreased bladder compliance due to disease progression. This may preclude patients from using this device. In sum, our experience has shown that patient selection, education and support are crucial to successful device acclimatization and that, despite the effort required, the encouraging improvement in QOL makes the whole endeavour worthwhile. 5. Conclusions The In-Flow catheter appears to be a viable treatment alternative to CIC for a subgroup of female patients with a hypocontractile or acontractile bladder. A subgroup of patients, mainly those unsatisfied with the currently available treatments, were more likely to tolerate this device and may achieve increased independence, improved self-esteem and an overall enhancement of their QOL. References [1] Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J Urol 1972;107(3): [2] Wyndaele JJ, Maes D. Clean intermittent self-catheterization: a 12-year followup. J Urol 1990;143(5): [3] Madjar S, Halachmi S, Wald M, Issaq E, Moskovitz B, Beyar M, et al. Long-term follow-up of the in-flow trade mark intraurethral insert for the treatment of women with voiding dysfunction. Eur Urol 2000;38(2): [4] Schurch B, Suter S, Dubs M. Intraurethral sphincter prosthesis to treat hyporeflexic bladders in women: does it work? BJU Int 1999;84(7): [5] Madjar S, Sabo E, Halachmi S, Wald M, Issaq E, Moskovitz B, et al. A remote controlled intraurethral insert for artificial voiding: a new concept for treating women with voiding dysfunction. J Urol 1999;161(3): [6] Lynch WJ, Testa GA, Bell DF. The subjective and objective benefits of a remote-controlled intraurethral device for managing the female acontractile bladder. BJU Int 2003;92: [7] Wagner TH, Patrick DL, Bavendam T, et al. Quality of life of people with urinary incontinence: the development of a new measure. Urology 1996;47(1): [8] Nitti VW, Raz S. Urinary retention. In: Raz S, editor. Female Urology. 2nd Ed. Philadelphia: Saunders; p [9] Resnick NM, Yalla SV. Geriatric incontinence and voiding dysfunction. 8th ed. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, editors. Campbell s Urology, vol. 2. Philadelphia: Saunders Publishing; p [10] Patrick DL, Martin ML, Bushnell DM, Yalcin I, Wagner TH, Buesching DP. Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QOL). Urology 1999;53(1):71 6, (Erratum in: Urology 1999;53(5):1072).