Advice
Clinical and technical evidence
Clinical and technical evidence
A literature search was carried out for this briefing in accordance with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.
Published evidence
This briefing summarises 11 studies, including 1 systematic review of other studies relating to Memokath‑028 (Armitage et al. 2006). Nine of the included studies recruited men only (the other 2 studies did not state the sex of the patients; Wong et al. 2014, Hamid et al. 2003). Wong et al. (2014) used Memokath‑044, so it is reasonable to assume that this study also included only men.
Tables 2 to 4 summarise the clinical evidence and its strengths and limitations.
Overall assessment of the evidence
Memokath‑028
The evidence base is of limited quality with relatively short follow-up periods. There is also a lack of evidence with relevant comparators. However, the existing evidence does suggest that Memokath‑028 is a safe and effective treatment for urethral obstruction, particularly for people with benign prostatic hyperplasia who are at high risk from surgery. The evidence also suggests that the device may be able to increase both urinary flow rate and urinary volume. Few adverse events were reported with Memokath‑028; the most common adverse event was stent migration, which appeared to be associated with the length of time that the stent remains in place.
Memokath‑044
The evidence suggests that Memokath‑044 may lead to improvements in urinary flow rate and a reduction in post-void residual urine volume. However, the studies are contradictory in their conclusions: 2 support the use of the device and 2 do not, with 1 recommending that the stent should only be used on a temporary basis and the other suggesting that Memokath‑044 is neither safe nor clinically helpful. Encrustation appears to be the most commonly reported adverse event. Although there is evidence from 1 randomised controlled trial, the study is relatively small with high withdrawal rates. All the other studies are small-scale and non-comparative.
Memokath‑045
All 3 studies suggest that Memokath‑045 is safe and effective, and a good medium-term option for urinary obstruction in the context of spinal cord injuries. All 3 studies reported a decrease in post-void residual urine volume. The most commonly reported adverse events were urinary tract infections and stent failure because of stent migration. However, the current evidence base is limited because the studies were relatively small, poorly designed and conducted.
Table 2 Summary of included studies for Memokath‑028
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Study size, design and location |
Systematic review including 14 single-arm observational studies with a total of 839 men. Most patients had urethral obstruction because of BPH, although some studies included those with prostate carcinoma. Studies included in the review were done in Japan, the UK, Denmark, Germany and Greece. |
|
Intervention and comparator(s) |
Intervention: Memokath‑028. Comparator: none. |
|
Key outcomes |
240 (29%) of the 839 stents inserted failed. Immediate failure of the stent occurred in 11 (4%) of the 311 patients, mainly because of incorrect stent length or placement. Failure rates varied widely across the included studies. Two studies reported no stent failure (over follow-up periods of 8 weeks and 14 months), while the highest reported failure rate was 48% (length of follow-up not reported) and 41% (over a mean follow-up of 7 months). 7 studies reported increases in post-insertion Qmax of 3–11 mL/s, although the timing of assessments varied. Two additional studies reported increases in mean flow rate. 4 studies reported decreases in post-void residual urine volume and 1 study reported an increase in total voided urine volume. All 7 studies reporting symptom scores noted a reduction in symptoms after stenting, associated with reductions of 11–19 points in IPSS scores and 9 points in the Madsen–Iversen score. The statistical significance of these changes was variable and poorly reported at times, but 2 studies reported that IPSS scores were significantly improved after stenting (p<0.05) but not after 8 and 24 weeks of follow-up. Stent migration was the most commonly reported cause of stent failure. Urinary incontinence, infection and haematuria were the most commonly reported minor complications. |
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Strengths and limitations |
Systematic review study design. Poor methodological quality of included studies; review conducted using funding from PNN Medical, although the authors acted independently in the conduct and publication. Overall numbers of patients experiencing changes in urodynamic measures were not reported. |
|
Study size, design and location |
Observational study conducted in 10 men with obstructive voiding symptoms after receiving brachytherapy for prostate cancer in a single centre in the Netherlands. |
|
Intervention and comparator(s) |
Intervention: Memokath‑028 inserted within the first 6 months after brachytherapy. Comparator: none. |
|
Key outcomes |
In 5 patients who did not have a catheter before stent placement, mean Qmax was 11.2 mL/s at 3 months post-insertion compared with 4.7 mL/s before stent insertion. In 5 patients who did have a catheter before stent placement it was not possible to measure urinary flow rate before stent insertion; however, mean Qmax at 3 months post-insertion was 15 mL/s. Mean IPSS and quality-of-life scores improved from baseline to 3-months in patients who did not have a catheter before stent placement (reduced from 29 to 11 for IPSS and 5 to 1 for quality of life). No encrustation was seen at a follow-up time of 6 months post-insertion. 2 stents migrated towards the bladder within 2 days of insertion. In 4 patients, stents were removed at 6 months post-insertion as they experienced minor irritative symptoms, but the patients indicated that they were more satisfied with the stent than before insertion. Perineal pain and irritative voiding were reported in 5 patients and UTI in 1. |
|
Strengths and limitations |
Relatively short follow-up period (6 months); small sample size; non-comparative study design. |
|
Study size, design and location |
Observational study conducted in 2 centres in Japan, including 37 older men with urethral obstruction at high risk from surgery who were previously managed with long-term catheterisation. |
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Intervention and comparator(s) |
Intervention: Memokath prostate stent. Comparator: none. |
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Key outcomes |
Mean (SD) post-void residual volume was 42.7 (66.0) mL (n=34) after stent insertion and 26 patients had a post-void residual volume <50 mL [post-void residual volumes before stent insertion not reported]. Pyuria was present in all patients before stent insertion. Following stent placement, pyuria was absent in 54.3% patients and no patients had serious symptoms of the disorder. 21 patients (56.7%) were able to urinate unassisted following stent insertion at a mean follow-up time of 33.2 months. 16 patients (43.3%) could not urinate unassisted in the long-term for reasons including stent migration, other adverse events, onset of urethral cancer and lowered ability to perform everyday activities (unrelated to presence of the stent). In 7 patients stents migrated within 3 months of insertion and were removed. Five of these patients had a total prostate volume <20 mL and the authors suggested that patients with lower prostate volume may be more vulnerable to stent migration. Encrustation was not observed in any patients. Other adverse events reported were urinary incontinence (n=6), haematuria (n=1) and persistent UTI that developed into sepsis (n=1). |
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Strengths and limitations |
Non-comparative study design. |
|
Study size, design and location |
Retrospective observational study conducted in Japan, including 127 older men with bladder outflow obstruction because of BPH (84%) or prostate carcinoma (16%) who were at high risk from surgery. |
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Intervention and comparator(s) |
Intervention: Memokath‑028. Comparator: none. |
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Key outcomes |
41% of stents had to be removed because of encrustation (15%), migration (10%), penile pain (6%), bladder outlet obstruction (5%), urinary incontinence (<3%), tissue granulation (<3%), recurrent UTIs (<3%) or urethral stricture (<3%). Mean indwelling time for a single stent was 1 year. Mean Qmax was 14.6 mL/s compared with 7.6 mL/s before stent insertion. Mean residual urine volume was 21 mL compared with 147 mL before stent insertion. Mean IPSS and quality-of-life index were 12 points and 2 points, respectively, compared with 25 and 5.1 points before stent insertion. |
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Strengths and limitations |
Long study follow-up (mean follow-up was 6 years). Retrospective, non-comparative study design; occurrence of outcomes are only reported as percentages, rather than absolute numbers. |
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Abbreviations: BPH, benign prostatic hyperplasia; IPSS, International Prostate Symptom Score; SD, standard deviation; Qmax, maximum urinary flow rate; UTI, urinary tract infection. |
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Table 3 Summary of included studies for Memokath‑044
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Study size, design and location |
Observational study conducted in Egypt, including 23 men with recurrent bulbar urethral stricture. |
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Intervention and comparator(s) |
Intervention: Memokath‑044 stent. Comparator: none. |
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Key outcomes |
Mean (SD, range) flow rate was 21 (2.5, 17 to 25) mL/s post-insertion compared with 4.6 (1.2, 3 to 7) mL/s before stent insertion. Mean (SD, range) post-void residual volume was 50 (14, 30 to 70) mL post-insertion compared with 165 (19, 130 to 190) mL before stent insertion. Overall, stents failed in 12 patients (52%); 8 were because of adverse events and 4 patients felt uncomfortable and requested removal. In 3 patients (13%) stents were obstructed during the first 6 months of follow-up because of encrustation. The mean (SD) period for encrustation was 9.8 (2) months. In 5 patients (22%) stents migrated and were exchanged. Migration was related to accidental perineal trauma, a faulty trial of catheterisation, and the presence of the stricture close to the sphincter. The mean (SD) period for migration was 10 (3) months. Other adverse events reported were perineal pain that was transient and ceased within a few weeks (n=6), urethral hyperplasia leading to stent removal (n=2), UTIs (n=4) and intermittent gross haematuria (n=3). |
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Strengths and limitations |
Low number of patients; non-comparative study design. |
|
Study size, design and location |
Multicentre randomised controlled trial conducted in the US, including 92 men with recurrent bulbar urethral stricture. |
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Intervention and comparator(s) |
Intervention: dilation or internal urethrotomy followed by insertion of Memokath‑044 stent. Scheduled stent removal at 12 months post-insertion (Memokath group, n=63). Comparator: dilation or internal urethrotomy followed by urinary catheter drainage for approximately 1 week (n=29). |
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Key outcomes |
Median time to urethral patency failure (inability to pass a 16Fr cystoscope through the strictured region) was 292 days in the Memokath group compared with 84 days in the control group (p=0.002). Normal urinary flow rates were achieved in 39 Memokath‑044 patients (66.1%) and 16 control patients (55.3%) after treatment. At 3, 6, 9 and 12 months of follow-up 60.3%, 50.0%%, 43.2% and 36.1% of Memokath patients respectively remained within the normal range of urinary flow rates (as defined by the Siroky nonogram). Comparable figures were not provided for the control group. Mean AUASI scores improved to normal levels in both groups following treatment. Up to 30% of patients in the Memokath group reported transient pain immediately after stent insertion, which decreased significantly during follow-up. Severe pain was reported by 1 patient. Encrustation was observed in 25.9% of Memokath patients. However, only 3 of these cases led to clinically significant decreases in mean Qmax and mean Qavg. Stents were dislocated in 8 patients (12.6%). Minor stent movements of up to 1 cm were observed in 12 patients (19.1%). It was not reported whether any of these migrations were clinically significant and necessitated intervention. 31 Memokath patients experienced bacteriuria compared with only 2 patients in the control group. Most (39 out of 53) of these cases were rated as mild, although 1 instance was severe. 10 Memokath patients (15.9%) experienced haematuria versus 3.4% of control group patients. Incontinence occurred in 19% of Memokath patients, although this was not considered significant based on IIQ-7 responses. |
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Strengths and limitations |
Randomised, controlled study design. High rates of withdrawal, particularly in the control group (patients were withdrawn after stricture reoccurrence) meant that follow-up was incomplete and comparisons between groups are less reliable; study was funded by the company. |
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Study size, design and location |
Prospective observational study conducted in Australia, including 22 patients (gender not stated) with recurrent bulbar urethral strictures who had previously undergone dilation or urethrotomy. |
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Intervention and comparator(s) |
Intervention: dilation or urethrotomy followed by insertion of a Memokath‑044 stent. Scheduled removal of the stent after 3 months. Comparator: dilation or DVIU alone conducted previously in the same patient population (n not reported). |
|
Key outcomes |
Mean Qmax 3 months post-insertion was 33.1 mL/s, compared with 4.5 mL/s before stent insertion. Mean Qmax decreased at 6 and 12 months post-insertion to 31.8 mL/s and 28.4 mL/s, respectively (not statistically significant). Strictures recurred in 5 patients (22%). Two further patients complained of lower urinary tract symptoms at 15 and 18 months post-insertion. Kaplan-Meier survival analysis was performed examining stricture and symptom recurrence. The mean (SD) time to recurrence without stenting was 2 (0.4) months versus 23 (2.5) months when a stent was inserted [reported that this was 'highly significant' but no p value given]. No patients had significant stent encrustation. In 1 patient stent migration occurred at 10 weeks post-insertion and the stent was removed. |
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Strengths and limitations |
Prospective study with some use of comparative data, although the study design was non-comparative. Poor quality of reporting: statistical significance was reported without p values, numbers of patients included in analyses was not always stated, and figures and data presented within them were not fully explained. |
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Study size, design and location |
A phase IIa pilot study conducted in Italy, including 16 men with recurrent bulbar urethral stricture who had previously undergone treatment. |
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Intervention and comparator(s) |
Intervention: Urethrotomy (n=4) or dilation (n=12) followed by insertion of a Memokath‑044 stent. Scheduled stent removal at 12 months post-insertion. Comparator: none. |
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Key outcomes |
Mean (range) time of stent retention was 10 (4–13) months. Median (range) Qmax was 11 (3.8-33.7) mL/s post-insertion, compared with 5.8 (2.0–8.6) mL/s before stent insertion. 11 patients (69%) had to undergo internal urethrotomy in spite of stenting. Also, 1 stent had to be removed because of intra-stent stricture. No statistically significant differences were found in mean symptom scores relating to voiding, storage, and urinary leakage before and after stent insertion. Encrustation was reported in 5 patients (31%), although this was only sufficient to need removal in 1 case. In 1 patient the stent was removed because of dislocation into the penile urethra. Other adverse events reported were chronic pain 4 to 9 months after implantation (n=5) and bacteriuria (n=5). |
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Strengths and limitations |
Thorough reporting of stent-related complications; prospective study design. Small sample size; potential effect of learning curve (surgeon inexperienced in insertion of the stent); non-comparative study design. |
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Abbreviations: AUASI, American Urological Association Symptom Index; IIQ-7,Incontinence Impact Questionnaire-Short Form; SD, standard deviation; Qavg, average urinary flow rate; Qmax, maximum urinary flow rate; UTI, urinary tract infection. |
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Table 4 Summary of included studies for Memokath‑045
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Study size, design and location |
Retrospective observational study conducted in the UK, including 25 patients (gender not stated) with DSD following spinal cord injury. |
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Intervention and comparator(s) |
Intervention: Memokath‑045. Comparator: none. |
|
Key outcomes |
19 stents were removed over the course of follow-up, 9 within 2 years post-insertion and 10 between 2 and 3 years post-insertion. Reasons for stent removal were migration (n=7), encrustation and stone formation (n=5), autonomic dysreflexia (n=3), incomplete bladder emptying (n=3), and issues with fertility (n=1). Six patients (24%) had a functioning stent in place at a mean follow-up time of 34.7 months. Mean (SD) maximum detrusor pressure at 6 months post-insertion was 61.8 (16.6) cmH2O compared with 79.1 (44.3) cmH2O before stent insertion (p<0.05). Mean (SD) duration of detrusor contraction at 6 months post-insertion was 79.3 (37.2) seconds compared with 116 (53.6) seconds before stent insertion (p<0.05). Mean (SD) residual urine volume at 6 months post-insertion was 155 (174.9) mL compared with 362.5 (320.3) mL before stent insertion (p<0.05). 2 patients experienced severe autonomic dysreflexia symptoms within 3 weeks of insertion and the stents were removed. However, all remaining patients experienced a decrease in autonomic dysreflexia-like symptoms (headaches, sweating and hypertension). There were 15 cases of UTI before stent placement, with 10 improving post-insertion. In 3 patients at a mean (range) of 25 (22-29) months the bladder did not generate sufficient pressure to empty and recurrent UTIs occurred. Stents in these patients were removed. There were no cases of hydronephrosis post-insertion compared with 4 cases before stent placement. |
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Strengths and limitations |
Rigorous reporting of outcomes, including tests for statistical significance; UK setting. Non-comparative study design. |
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Study size, design and location |
Observational study conducted in Switzerland, including 22 men with urinary dysfunction following spinal cord injury. |
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Intervention and comparator(s) |
Intervention: Memokath stent. Comparator: none. |
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Key outcomes |
Mean residual urine volume was 105 mL post-insertion compared with 229 mL before stent insertion (p=0.0075) (n=18). Fourteen patients (77.8%) had residual urine <100 mL (classified as successful) during follow-up. Mean (SD) maximum detrusor pressure was 64.7 (34.5) cmH2O post-insertion compared with 61.1 (47.2) cmH2O before stent insertion (p=0.484) (n=18). Retrograde external sphincter perfusion pressure was 61 cmH2O compared with 70 cmH2O before stent insertion (p=0.008; n=18). The rate of symptomatic UTIs was 1.2 in 6 months after stent insertion, compared with 4.3 in 6 months before. |
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Strengths and limitations |
Reporting of outcomes includes tests for statistical significance. Non-comparative study design. |
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Study size, design and location |
Retrospective observational study conducted in South Africa, in 28 men with bladder dysfunction following spinal cord injury. |
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Intervention and comparator(s) |
Intervention: dual-flange Memokath stent. Comparator: none. |
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Key outcomes |
15 (45%) of the 33 stents placed were removed during the mean follow-up time of 18 months. The mean (range) time to stent failure was 15.7 (0.25 to 38.0) months. Stents failed because of stone formation (n=7), migration (n=3), large post-void residual urine volume (n=3), haematuria (n=1), and autonomic dysreflexia (n=1). In patients with stent placement lasting more than 20 months (n=11) mean (range) post-void residual volume decreased from 143 (32 to 330) to 2.5 (0 to 28) mL. In patients with stents removed before 20 months (n=10), mean (range) post-void residual volume decreased from 222 (32–330) to 122 (0–28) mL. There were 7 cases of autonomic dysreflexia post-insertion compared with 17 cases before stent placement (p=0.003). One patient (3%) experienced severe autonomic dysreflexia post-insertion and the stent was removed. There were 7 cases of UTI post-insertion compared with 22 cases before stent placement (p<0.001). There was 1 case of hydronephrosis post-insertion compared with 2 cases before stent placement. |
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Strengths and limitations |
Non-comparative study design. |
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Abbreviations: DSD, detrusor sphincter dyssynergia; SD, standard deviation; UTI, urinary tract infection. |
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Overall, the evidence base for Memokath stents is limited, with poor study design and very few comparative trials. Future randomised controlled trials comparing Memokath stents with standard care (including prostatic and urethral surgery and self- and indwelling catheterisation) and with other stents for treating urethral obstruction would be useful to provide more evidence. Trials with follow-up of more than 1 year would provide evidence on longer-term outcomes.