Between August 2013 and May 2018, a total of 33 participants were enrolled in the study out of which 29 completed all study visits according to protocol. Four participants prematurely terminated the study; one person due to an adverse event possibly related to the medical device. Three of those four patients withdrew consent owing to pain in lower extremity after saline irrigation, post-irrigation bladder irritation on day 2 and abdominal cramps after the fourth irrigation, respectively. The fourth patient was excluded from the study by the responsible investigator due to an adverse event possibly related to the medical device (urinary infection).
- Patient Demographics and baseline characteristics
As one of the participants was excluded due to pain in the lower extremities after irrigation with saline, 32 participants received at least one treatment with the active ingredient and were therefore included in the analysis. Twenty-four (75 %) of these 32 participants were male and eight (25 %) were female. The mean age of the patients was 59.3 ± 13.2 years. All included participants had undergone urethral (n = 10) or suprapubic (n = 22) catheterization more than 2 weeks before the screening visit. Six patients were catheterized for more than 60 months at the time of screening. The most frequent medical conditions leading to catheter insertion were multiple sclerosis (n = 10), or spinal cord injury (n = 12) (Table 1).
There was no incidence of a serious adverse event in the study. A total of 28 adverse events (AEs) were experienced by 15 (46.88%) of the participants (Table 2). Of those 15 persons, eight persons experienced a single AE while seven patients experienced more than one AE.
The intensities of all AEs were either mild (n=17, 61 %) or moderate (n=11, 39 %) in nature (Table 2). Most of the adverse events were isolated in occurrence (n = 21, 75 %) while seven (n=7, 25 %) AEs were classified as intermittent. All but one AEs (96.4 %) were resolved with no sequelae by the end of the study. Of the 27 AEs which were resolved, 23 required no
intervention, 2 were administered concomitant medications and for 1 AE the study product was stopped. One AE (spasms) was not resolved by the end of the study. However, persistence of spasms experienced by the patient further than the time of the treatment were diagnosed by the PI to be related to an underlying disease and not to the device, and thus a follow-up was not applicable.
Among the 28 reported AEs, 22 (78.6%) were classified as Adverse Device Effects (ADEs). For these 22 ADEs, the association between the AEs and the medical device was classified as possible (n=16; 72.7%), probable (n=2; 9.1%) and certain (4; 18.2%). The ADEs were experienced by 10 patients, four of which experienced one ADE each and six more than one ADE. ADEs were related to renal and urinary disorders. None of the ADEs were related to urticaria, exanthema or other allergic reactions.
There was no incidence of a serious adverse event in the study. A total of 28 adverse events (AEs) were experienced by 15 (46.88%) of the participants (Table 2). Of those 15 persons, eight persons experienced a single AE while seven patients experienced more than one AE.
The intensities of all AEs were either mild (n=17, 61 %) or moderate (n=11, 39 %) in nature (Table 2). Most of the adverse events were isolated in occurrence (n = 21, 75 %) while seven (n=7, 25 %) AEs were classified as intermittent. All but one AEs (96.4 %) were resolved with no sequelae by the end of the study. Of the 27 AEs which were resolved, 23 required no
intervention, 2 were administered concomitant medications and for 1 AE the study product was stopped. One AE (spasms) was not resolved by the end of the study. However, persistence of spasms experienced by the patient further than the time of the treatment were diagnosed by the PI to be related to an underlying disease and not to the device, and thus a follow-up was not applicable.
Among the 28 reported AEs, 22 (78.6%) were classified as Adverse Device Effects (ADEs). For these 22 ADEs, the association between the AEs and the medical device was classified as possible (n=16; 72.7%), probable (n=2; 9.1%) and certain (4; 18.2%). The ADEs were experienced by 10 patients, four of which experienced one ADE each and six more than one ADE. ADEs were related to renal and urinary disorders. None of the ADEs were related to urticaria, exanthema or other allergic reactions.
1.1. Tolerability and other safety parameters
VAS scores recorded for all participants having sustained sensation in the bladder were either zero or low for all visits, instillations and time-points. Absolute changes in VAS scores for all patients, visits and irrigation-types were less than 20 mm and, therefore, were not clinically relevant. No incidence of either flushing or sweating for any participant during any instillation was observed. Bladder spasms during instillation were reported in two cases, each at a single instillation. Four participants, who reported 9 incidences, reported them as moderate or mild. These spasms were experienced during a single instillation with UT-PHMB per patient and the patients did not reported any further incidences in the subsequent instillations. Additionally, no patient reported bladder spasms on the day of the final assessment.
Mean pulse rates of all study participants measured before, immediately after and 5 minutes after irrigation for any instillation with either saline solution or UT-PHMB did not change by more than 3 beats per minute (figure 1).
Absolute change in body temperature before and 15 minutes after irrigation was less than 2 °C across all visits and instillations for all but one participant who showed an increase of 2.1 °C in body temperature after the UT-PHMB instillation on study day 2 but did not show any signs of infection or any other signs of discomfort. Mean changes in body temperature did not exceed 0.12 °C in any comparison of pre - and post - irrigation temperatures.
Mean systolic blood pressure during days 1-5 measured at different time points differed from the mean systolic blood pressure at screening (120.1 ± 17.5) by a maximum of 8 mmHg (figure 2). Clinically relevant changes in blood pressure were recorded for 3 patients. The blood pressure of one participants decreased by 53 mmHg after one irrigation while an increase was observed for the other two patients (40 mmHg and 70 mmHg, respectively) after irrigation with the device.