Hypothesis / aims of study
The Artificial Urinary Sphincter (AUS) is currently the gold standard for the treatment of severe stress urinary incontinence (SUI) in men [1]. The most widely AUS implanted worldwide is the AMS 800 (Boston Scientific, USA). This device is a passive hydraulic device, where the urethral occlusion pressure is transmitted by the Pressure Regulating Balloon (PRB). PRB pressure is fixed, usually with a range of 61- 70 cm H2O as a consensus validated value [2] and cannot be adjusted after implantation. The clinical effectiveness of the device has been well-established in both men and women. However, there is a significant rate of revisions and explantations, along with ergonomic concerns.
The UroActive AUS (UroMems, Grenoble, France) is an active implantable medical device. It consists of an occlusive cuff (OC) connected to a Control Unit (CU). The CU incorporates a reservoir, a pump, a battery and electronic components to enable wireless communication (Fig 1). The OC is placed around the bulbar urethra by a perineal incision and the CU is placed in the right part of the abdomen above the aponeurosis, so no intra-abdominal surgery is required (Fig 2).
The patient can void and control the level of the device pressure using a dedicated Patient Remote Control (PRC). Two levels of pressure can be set: a Baseline Pressure applied during everyday activities or a Low Pressure applied when lying down. Each level of pressure can be personalized at any time with the CP.
The device implements a failsafe function UroTimer allowing the device to be automatically deactivated if the patient does not void for a certain period of time (eg 12hours).
Data, including device pressure and PRC use, are recorded by the device and can be downloaded with the CP.
The aim of this clinical study was to assess the safety and effectiveness of the new AUS device, UroActive, at 6 months post-activation. Uroactive is neither CE-marked nor FDA-approved yet.
Study design, materials and methods
This study is a prospective, open-label, multi-center, single-arm study designed to assess the safety and the effectiveness of UroActive in 6 patients (NCT05547672, French Ethic Committee 22.02260.000065).
After the implantation and a healing period of 5 weeks +/- 1 week, the device is activated. Follow-up visits are planned at 14 days and then at 1-, 3- and 6- months post-activation to assess the patients’ continence level and potentially adjust the device parameters according to patients’ feedback.
Primary clinical outcomes are:
• Rate of explants and revisions at 6 months after device activation
• Rate of device activation successes.
Main secondary clinical outcomes are:
• Number of subjects with 50% reduction or greater in 24-hour pad weight test (24H-PWT) at 3 and 6 months after device activation.
• Number of subjects with 75% reduction or greater in 24-hour pad weight test (24H-PWT) at 3 and 6 months after device activation.
• QoL Questionnaires (ICIQ-UI SF, ICIQ-MLUTS, ICIQ-MLUTSsex, EQ-5D3L, I-Qol and USP) at Baseline, 3-months and 6-months post-activation.
• Rate of Adverse Events (AE).
We report the results at 6 months post-activation.
Results
The study started September 2022.
Patients had a median age of 71 years (IQR, 66-73 years) with a median BMI (kg/m2) of 25.3 (IQR, 24.5-26.4). Two patients had a medical history of diabetes. All had a sphincter deficiency after radical prostatectomy. One patient had a history of previous SUI surgery. No patient had prior radiotherapy. Median time between urinary incontinence onset and study baseline was 4.5 years (IQR, 2.0-7.0). At baseline, the median maximal urethral closure pressure was 34.5cm H2O (IQR, 24.0-38.0) and results of the 24H-PWT showed a median urine loss of 465g (IQR, 99-1059), respectively.
All devices were implanted and activated successfully. Median operative time was 64minutes (IQR, 60 - 66). 5 patients stayed one-night post-operatively and the last patient was implanted in an outpatient surgery setting.
At 6 months post- activation:
• All devices were successfully activated.
• All patients had a 24H-PWT reduction of more than 50%
• 5 of the 6 patients had a 24H-PWT reduction of more than 75%
• Median maximum flowrate and post-voiding residual volume were 36ml/s (IQR, 25-41) and 0ml (IQR, 0-0), respectively.
• Median scores from the QoL questionnaires, compared to baseline, are reported in Table 1.
According to data downloaded from the CU:
• Patients performed a median of 8,1 micturition/day (IQR, 8.0 -8.7) .
• They spent a median of 7.2 hours/24hours (IQR, 6.0 – 8.0) using the low-pressure setting in the device.
• Median estimated pressure in the devices during the 6 months was 50cm H20 (IQR, 43 – 54).
Preliminary safety profile highlights 2 Severe Adverse Events (SAE):
• One related to the device (post-operative dysuria during 24H)
• One unrelated to the device (syncope)
UroTimer safety function was triggered 4 times:
• 3 times because of pre-setting being too short ()
• One time following a SAE (syncope unrelated to the device).
All devices were reactivated subsequently without any difficulties.
Interpretation of results
The SOPHIA study showed that the UroActive AUS can be easily implanted, activated and post-operative adjustment of cuff pressure can be done.
Moreover, data demonstrated that the treatment of SUI was effective with a low complication rate.