Urinary Retention
Conditions
Brief summary
A multi-centre, randomized, controlled crossover design. The total study duration for the individual subject was approximately 9 weeks. The study consisted of four study visits (V0-V3) and two 4-week test periods at home (T1 and T2). Visit 0 and 1 was performed on the same day if subjects allowed. One population included all enrolled subjects who took part in the two test periods in a home setting only (T1 and T2). This constituted the Full Analysis Set (FAS) 1 (N=73)where only endpoints related to dipstick hematuria, catheter perception and quality of life were assessed. A subset of subjects from the FAS1 also took part in two clinic visits (V2 and V3) where endpoints related to bladder emptying and discomfort were assessed. One visit took place in between the two test periods at home (V2) and the other visit took place after the last test period at home (V3) which was also the termination visit. This subset is termed the FAS 2 (N=49).
Detailed description
This investigation was a multi-centre, randomized, controlled crossover study including 73 male clean intermittent catheterization (CIC) users. The study consisted of four study visits (V0-V3) and two 4-week test periods at home (T1 and T2). Visit 0 and 1 were performed on the same day if participants allowed. Visit 0 included the screening-, inclusion-, and randomization phase of participants and at visit 1, participants performed a self-catheterization with the device according to their respective randomization scheme. This was followed by a dipstick test for hematuria. This constituted the Full Analysis Set (FAS) 1, consisting of 73 participants. In the two 4-week test periods (T1 and T2, respectively) the participants catheterized at home with the specified catheter according to their randomization scheme. Both 4-week periods started with a 2-week run-in period followed by a 2-week period during which a dipstick test for hematuria was performed daily. For Visit 2 and 3, a sub-group of participants was invited for a clinical test visit during which participants were catheterized with the same device applied during the preceding home-test period. First a healthcare professional (HCP)-led catheterization was performed followed by a self-catheterization, and endpoints related to bladder emptying (residual urine and number of urinary flow-stop episodes) were measured. After each catheterization, any residual urine left in the bladder was measured with a bladder scanner and hematuria was assessed with a dip-stick test. After the self-catheterization process, subjects at clinic visit V2 and V3 completed a questionnaire related to discomfort.This constituted the Full Analysis Set (FAS) 2, consisting of 49 participants. All participants completed a perception questionnaire and a HRQoL questionnaire associated with the catheter during the last two weeks of the home test period. For participants not part of clinic visits V2 and V3, a nurse assisted with the questionnaires after each home-test period during a remote home visit. Thereafter, all participants were introduced to the second device to be tested for the next home-test period. After the second home-test period, the study was terminated with a test visit 3 (V3), either in the clinic (for the subset group, FAS2) or a home visit by the nurse (the FAS1 group).
Interventions
DEVICEInvestigational device - intermittent catheter with micro-hole zone
Intermittent male catheter with micro-hole zone for urinary drainage
DEVICEComparator - standard intermittent catheter
SpeediCath Flex, VaPro Pocket, VaPro Plus and VaPro Plus Pocket.
Sponsors
Coloplast A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This was a multi-centre, randomized, controlled crossover design. The total study duration for the individual participant was approximately 9 weeks. The study consisted of four study visits (V0-V3) and two 4-week test periods at home (T1 and T2). Visit 0 and 1 was performed on the same day if subjects allowed. One population included all enrolled subjects who took part in the two test periods in a home setting only (T1 and T2). This constituted the Full Analysis Set (FAS) 1 (N=73) where only endpoints related to dipstick hematuria, catheter perception and quality of life were assessed. A subset of subjects from the FAS1 also took part in two clinic visits (V2 and V3) where endpoints related to bladder emptying and discomfort were assessed. One visit took place in between the two test periods at home (V2) and the other visit took place after the last test period at home (V3) which was also the termination visit. This subset is termed the FAS 2 (N=49).
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Male 2. Was at least 18 years of age and had full legal capacity 3. Had given written informed consent 4. Had signed letter of authority (only DK) 5. Had used clean intermittent self-catheterization (CISC) for at least the last 3 months 6. Had used intermittent catheterization as the only bladder emptying method for at least the last 3 months 7. Self-catheterized using Coloplast SpeediCath Flex or Hollister VaPro catheters, CH12 or CH14, for at least 3 months prior to inclusion 8. Had the ability (assessed by investigator) and willingness to adhere to a 2-month study period
Exclusion criteria
1. Participation in any other clinical study during this investigation 2. Previous participation in the study 3. Symptoms of urinary tract infection as judged by the investigator (rescheduling allowed within recruitment period for LPI) 4. Individuals with history, suspected or showing signs of producing urine with excessive amount of mucus or large/clustered sediments or debris 5. Any known allergies towards ingredients in the investigational device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Residual Urine at 1st Flow Stop (HCP-led Catheterization) i.e., Total Catheterisation Volume Minus Volume at 1st Flow-stop, Both Derived From a Catheterisation Profile | Immediately after the procedure/catheterization, at second and third clinic visit following 4 weeks of home catheterization | The residual urine at 1st flow-stop during catheterization (performed by a HCP) represents the volume of urine left in the bladder, the first time the urine stops running out of the catheter during bladder emptying. Hence, the residual volume at 1st flow-stop was calculated as the total volume post catheterisation minus the volume at 1st flow-stop, derived from a catheterisation profile which was connected to a time-logged weighing \[g\]. |
| Number of Flow-stop Episodes (HCP-led Catheterization) | Immediately after catheterisation, at second and third clinic visit following 4 weeks of home catheterization | Number of flow-stop episodes were determined as instances where the flow rate decreased to less than 0.8 mL/s for a period of at least two seconds. All episodes were detected by automatic thresholding, followed by manual inspection, where the intra-catheter pressure readings were used to support the assessment of a flow stop. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Flow-stop Episodes (Self-led Catheterization) | Immediately after the procedure/catheterization, at second and third clinic visit following 4 weeks of home catheterization | Number of flow-stops were measured with a pressure sensor, which is an electronic device used for monitoring the hydrostatic pressure at the outlet of an intermittent urinary catheter during emptying. From a sensor curve, flow-stops were identified by two individually trained evaluators as a hydrostatic pressure peak coinciding with a urine flow-stop/ urine dripping (flowrate lower than 0,8 ml/sec). Results from both evaluators were compared and in case of discrepancy a discussion was performed to extenuate discrepancies and agree on a final interpretation of the curves. |
| Residual Urine at 1st Flow Stop (Self-led Catheterization) | Immediately after the procedure/catheterization, at second and third clinic visit following 4 weeks of home catheterization | The residual urine at 1st flow-stop during catheterization (performed by the participant self) represents the volume of urine left in the bladder, the first time the urine stops running out of the catheter during bladder emptying. Hence, the residual volume at 1st flow-stop was calculated as the total volume post catheterisation minus the volume at 1st flow-stop, derived from a catheterisation profile which was connected to a time-logged weighing \[g\]. |
| Mean Red Blood Cell Concentration | Dipstick test for haematuria was performed daily were performed in week 3 and 4 (1st home-period) and in week 7 and 8 (2nd home-period). | The average (mean) Red blood cell concentration based on a dipstick test, collected daily during the two weeks of the home test period T1 and T2 \[Erythrocytes/µL\]. |
| Positive Hematuria Event Post-catheterisation | week 3 and 4 (1st home-period) and in week 7 and 8 (2nd home-period). | Number of positive hematuria events (i.e., blood in urine) based on a dipstick test, collected daily during the final two weeks of the home test period T1 and T2 \[positive/negative scale\]. Positive value = blood in the urine. Negative value = no blood in the urine. |
Countries
Denmark, France, Germany, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Total ITT Population Baseline Measures As this study was a crossover study, each participant underwent catheterizations with both the investigational device and the comparator device. The study consisted of four study visits (V0-V3) and two 4-week test periods at home (T1 and T2). Visit 0 included subject screening, enrollment, and randomization. Randomization was done centralized, randomly assigning subjects to two intervention sequences in block-sizes of four. Hence, the first group was catheterized with the investigational device at visit 0 and 1, followed by a test period at home (T1) and a follow-up visit (V2). Subsequently, the comparator device was tested during the next test period at home (T2) followed by a visit 3 which also terminated the study. The second group tested the devices in reversed order. The total study duration was approximately nine weeks for the individual subject | 73 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 (V0, V1, T1, and V2) | Adverse Event | 1 | 1 |
| Period 1 (V0, V1, T1, and V2) | Withdrawal by Subject | 3 | 0 |
| Period 2 (T2 and V3) | Adverse Event | 0 | 1 |
| Period 2 (T2 and V3) | loss of contact | 0 | 1 |
Baseline characteristics
| Characteristic | Total ITT Population Baseline Measures | — |
|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 13.9 | — |
| Number of participants with neurogenic bladder dysfunction | 28 Participants | — |
| Number of participants with non-neurogenic bladder dysfunction | 45 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Denmark | 46 participants | — |
| Region of Enrollment France | 6 participants | — |
| Region of Enrollment Germany | 8 participants | — |
| Region of Enrollment United Kingdom | 13 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 73 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 73 | 1 / 73 |
| other Total, other adverse events | 8 / 73 | 8 / 73 |
| serious Total, serious adverse events | 3 / 73 | 0 / 73 |
Outcome results
Primary
Number of Flow-stop Episodes (HCP-led Catheterization)
Number of flow-stop episodes were determined as instances where the flow rate decreased to less than 0.8 mL/s for a period of at least two seconds. All episodes were detected by automatic thresholding, followed by manual inspection, where the intra-catheter pressure readings were used to support the assessment of a flow stop.
Time frame: Immediately after catheterisation, at second and third clinic visit following 4 weeks of home catheterization
Population: This population constituted a subset (= Full analysis set (FAS)2) of the all randomized subjects (FAS1, N=73). This subset FAS2 included 49 participant, who took part in both test periods at home (T1 and T2) and in clinic visits (V2 and V3) to acquire data related to the catheterization process and which supported the primary endpoints residual urine at first flow-stop and number of flow-stop episodes.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Investigational Device (Intermittent Catheter With Micro-hole Zone, CH12 or CH14) | Number of Flow-stop Episodes (HCP-led Catheterization) | 0.20 Flow stop episodes |
| Comparator Device (Standard Intermittent Catheter, CH12/14) | Number of Flow-stop Episodes (HCP-led Catheterization) | 1.32 Flow stop episodes |
Comparison: This was a superiority investigation in which the null hypothesis of the primary endpoints was to be rejected, at a 5% significance (alpha 0.05), to demonstrate the superiority of the investigational device.p-value: <0.00195% CI: [0.07, 0.35]Mixed Models Analysis
Primary
Residual Urine at 1st Flow Stop (HCP-led Catheterization) i.e., Total Catheterisation Volume Minus Volume at 1st Flow-stop, Both Derived From a Catheterisation Profile
The residual urine at 1st flow-stop during catheterization (performed by a HCP) represents the volume of urine left in the bladder, the first time the urine stops running out of the catheter during bladder emptying. Hence, the residual volume at 1st flow-stop was calculated as the total volume post catheterisation minus the volume at 1st flow-stop, derived from a catheterisation profile which was connected to a time-logged weighing \[g\].
Time frame: Immediately after the procedure/catheterization, at second and third clinic visit following 4 weeks of home catheterization
Population: This population constituted a subset (=Full Analysis Set 2(FAS2)) of the all randomized subjects (FAS1, N=73). This subset FAS2 included 49 participant, who took part in both test periods at home (T1 and T2) and in clinic visits (V2 and V3) to acquire data related to the catheterization process and which supported the primary endpoints residual urine at first flow-stop and number of flow-stop episodes.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Investigational Device (Intermittent Catheter With Micro-hole Zone, CH12 or CH14) | Residual Urine at 1st Flow Stop (HCP-led Catheterization) i.e., Total Catheterisation Volume Minus Volume at 1st Flow-stop, Both Derived From a Catheterisation Profile | 18 mL |
| Comparator Device (Standard Intermittent Catheter, CH12/14) | Residual Urine at 1st Flow Stop (HCP-led Catheterization) i.e., Total Catheterisation Volume Minus Volume at 1st Flow-stop, Both Derived From a Catheterisation Profile | 63.93 mL |
Comparison: This was a superiority investigation in which the null hypothesis of the primary endpoints was to be rejected, at a 5% significance (alpha 0.05), to demonstrate the superiority of the investigational device.p-value: 0.00195% CI: [19.24, 72.64]Mixed Models Analysis
Secondary
Mean Red Blood Cell Concentration
The average (mean) Red blood cell concentration based on a dipstick test, collected daily during the two weeks of the home test period T1 and T2 \[Erythrocytes/µL\].
Time frame: Dipstick test for haematuria was performed daily were performed in week 3 and 4 (1st home-period) and in week 7 and 8 (2nd home-period).
Population: Participants from the full analysis set during the first and second home period (FAS1)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Investigational Device (Intermittent Catheter With Micro-hole Zone, CH12 or CH14) | Mean Red Blood Cell Concentration | 16.25 erythrocytes per microliter |
| Comparator Device (Standard Intermittent Catheter, CH12/14) | Mean Red Blood Cell Concentration | 19.77 erythrocytes per microliter |
Secondary
Number of Flow-stop Episodes (Self-led Catheterization)
Number of flow-stops were measured with a pressure sensor, which is an electronic device used for monitoring the hydrostatic pressure at the outlet of an intermittent urinary catheter during emptying. From a sensor curve, flow-stops were identified by two individually trained evaluators as a hydrostatic pressure peak coinciding with a urine flow-stop/ urine dripping (flowrate lower than 0,8 ml/sec). Results from both evaluators were compared and in case of discrepancy a discussion was performed to extenuate discrepancies and agree on a final interpretation of the curves.
Time frame: Immediately after the procedure/catheterization, at second and third clinic visit following 4 weeks of home catheterization
Population: This population constituted a subset (FAS2) of the all randomized subjects (FAS1, N=73). This subset FAS2 included 49 participant, who took part in both test periods at home (T1 and T2) and in clinic visits (V2 and V3) to acquire data related to the catheterization process and which supported the primary endpoints residual urine at first flow-stop and number of flow-stop episodes.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Investigational Device (Intermittent Catheter With Micro-hole Zone, CH12 or CH14) | Number of Flow-stop Episodes (Self-led Catheterization) | 0.13 Flow stop episodes |
| Comparator Device (Standard Intermittent Catheter, CH12/14) | Number of Flow-stop Episodes (Self-led Catheterization) | 0.96 Flow stop episodes |
Comparison: This was a superiority investigation in which the null hypothesis of the primary endpoints was to be rejected, at a 5% significance (alpha 0.05), to demonstrate the superiority of the investigational device.p-value: <0.00195% CI: [0.04, 0.4]Mixed Models Analysis
Secondary
Positive Hematuria Event Post-catheterisation
Number of positive hematuria events (i.e., blood in urine) based on a dipstick test, collected daily during the final two weeks of the home test period T1 and T2 \[positive/negative scale\]. Positive value = blood in the urine. Negative value = no blood in the urine.
Time frame: week 3 and 4 (1st home-period) and in week 7 and 8 (2nd home-period).
Population: Participants from the full analysis set during the first and second home period, (FAS1).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Investigational Device (Intermittent Catheter With Micro-hole Zone, CH12 or CH14) | Positive Hematuria Event Post-catheterisation | 0.17 positive hematuria events |
| Comparator Device (Standard Intermittent Catheter, CH12/14) | Positive Hematuria Event Post-catheterisation | 0.19 positive hematuria events |
Secondary
Residual Urine at 1st Flow Stop (Self-led Catheterization)
The residual urine at 1st flow-stop during catheterization (performed by the participant self) represents the volume of urine left in the bladder, the first time the urine stops running out of the catheter during bladder emptying. Hence, the residual volume at 1st flow-stop was calculated as the total volume post catheterisation minus the volume at 1st flow-stop, derived from a catheterisation profile which was connected to a time-logged weighing \[g\].
Time frame: Immediately after the procedure/catheterization, at second and third clinic visit following 4 weeks of home catheterization
Population: This population constituted a subset (FAS2) of the all randomized subjects (FAS1, N=73). This subset FAS2 included 49 participant, who took part in both test periods at home (T1 and T2) and in clinic visits (V2 and V3) to acquire data related to the catheterization process and which supported the primary endpoints residual urine at first flow-stop and number of flow-stop episodes.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Investigational Device (Intermittent Catheter With Micro-hole Zone, CH12 or CH14) | Residual Urine at 1st Flow Stop (Self-led Catheterization) | 8.2 mL |
| Comparator Device (Standard Intermittent Catheter, CH12/14) | Residual Urine at 1st Flow Stop (Self-led Catheterization) | 36.8 mL |
Comparison: This was a superiority investigation in which the null hypothesis of the primary endpoints was to be rejected, at a 5% significance (alpha 0.05), to demonstrate the superiority of the investigational device.p-value: 0.00495% CI: [9.5, 47.6]Mixed Models Analysis