Urinary Retention, Urinary Tract Infections
Conditions
Keywords
tamsulosin, randomized controlled trials as topic, double-blind method, random allocation, placebos, Adrenergic alpha-Antagonists, urinary retention, urinary tract infections, urinary catheters, catheter-related infections, postoperative complications
Brief summary
The purpose of this study is to determine if tamsulosin (FLOMAX) is effective in preventing post-operative urinary retention following abdominal surgery. Post-operative urinary retention is a common post-operative complication, occurring in up to 30% of patients undergoing abdominal surgery. It can be described as the inability to initiate urination or properly empty one's bladder following surgery. It is usually self-limited, but it requires the use of catheterization to empty the bladder in order to prevent further injury to the bladder or kidneys and to relief the discomfort of a full bladder. Tamsulosin is a medication that is commonly used in men with urinary symptoms related to an enlarged prostate. There is some evidence to suggest that it may also potentially be beneficial for preventing post-operative urinary retention. Therefore, in this research study, subjects scheduled for abdominal surgery will be randomly assigned to take either tamsulosin once-daily or placebo once-daily for one week leading up to surgery, and up to several days after surgery. Urinary function will be assessed and compared between these two treatments. The hypothesis is that tamsulosin will reduce the rate of postoperative urinary retention compared to placebo.
Detailed description
Postoperative urinary retention (POUR) complicates up to 30% of general abdominal operations. It results in patient discomfort, embarrassment, interference with therapies, and significant nursing burden. More importantly, urinary retention necessitates use of intermittent catheterization or placement of an indwelling urinary catheter, which exposes the patient to an increased risk of urinary tract infection (UTI), urethral injury, and potentially increased hospital length of stay and cost. For these reasons, a safe and effective intervention for preventing POUR would be highly valuable. Despite such a need, no contemporary studies exist evaluating medications that can be used to prevent POUR in broad general surgery populations. To address this gap, the investigators have designed a prospective, randomized, double-blind, placebo-controlled trial to test the hypothesis that preoperative loading with tamsulosin will prevent POUR in patients undergoing elective, inpatient complex intra-abdominal surgery and thereby lead to improved short-term outcomes. Tamsulosin is a safe and widely-used selective alpha-1-A adrenergic blocker commonly used for the treatment of lower urinary tract symptoms in men with benign prostatic hypertrophy. It has also been shown to have some benefit in reducing POUR and need for catheterization in men undergoing inguinal hernia repair and other outpatient urologic procedures. This study is a randomized, double-blind, placebo-controlled trial in which patients scheduled for inpatient complex intra-abdominal surgery will be randomized to receive either tamsulosin or placebo for 7 days pre-operatively, and up to several days post-operatively, and then rates of POUR will be compared between the two groups (Aim 1). A retrospective analysis of the data will be used to identify risk factors for POUR and subgroups of patients that would derive the greatest benefit from preoperative tamsulosin (Aim 2). Furthermore, short-term outcomes, including rate of urinary tract infection (UTI) and hospital length of stay, will be compared between the tamsulosin and placebo groups (Aim 3). Enrolled subjects will be randomized using a blocked, stratified randomization process to either tamsulosin or placebo. Stratification variables include gender, pelvic vs non-pelvic surgery, and International Prostate Symptom Score (IPSS) survey results (which is a measure of baseline lower urinary tract symptoms). After a 7-day treatment period, subjects will undergo surgery as scheduled, and then the assigned treatment will be continued for up to a total of 14 days until the subject either has return of normal voiding function, has required replacement of an indwelling urinary catheter, or is discharged from the hospital.
Interventions
DRUGTamsulosin
Tamsulosin 0.4mg capsule orally once daily, dosed 30 minutes after dinner or before bed, starting 7 days before surgery and continuing for 0-5 days postoperatively. Outline of schedule: * Day 1-7: tamsulosin 0.4mg in the evening * Day 8: surgery; tamsulosin 0.4mg in the evening if the subject has not yet completed the bladder management protocol * Day 9-14: tamsulosin 0.4mg in the evening until the subject either 1) completes the bladder management protocol (defined by two consecutive voids with post-void residual \<200mL), or 2) has an indwelling urinary catheter replaced, or 3) is discharged from the hospital, whichever occurs first. The minimum number of total doses is 7; the maximum number of total doses is 14. The 14th dose will be the final dose regardless of bladder function.
DRUGPlacebo
Placebo capsule orally once daily, dosed 30 minutes after dinner or before bed, starting 7 days before surgery and continuing for 0-5 days postoperatively. Outline of schedule: * Day 1-7: placebo in the evening * Day 8: surgery; placebo in the evening if the subject has not yet completed the bladder management protocol * Day 9-14: placebo in the evening until the subject either 1) completes the bladder management protocol (defined by two consecutive voids with post-void residual \<200mL), or 2) has an indwelling urinary catheter replaced, or 3) is discharged from the hospital, whichever occurs first. The minimum number of total doses is 7; the maximum number of total doses is 14. The 14th dose will be the final dose regardless of bladder function.
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* English-speaking * Able to provide informed consent * Scheduled to undergo an elective, complex intra-abdominal operation with a planned postoperative inpatient stay of at least 1 night
Exclusion criteria
* Less than age 18 * Allergy or contraindication to tamsulosin * Serious sulfa allergy * Current use of alpha blocker (alfuzosin, doxazosin, prazosin, silodosin, terazosin, verapamil, tamsulosin) or oral alpha agonist (midodrine), or initiation of one of these medications during the intervention phase of the study will result in subject withdrawal from the study * Current warfarin use * Pre-existing indwelling urinary catheter, suprapubic catheter, or urostomy * End stage renal disease or dialysis-dependence * Sitting systolic blood pressure in the upper extremity of less than 100mm Hg at time of eligibility screening * Presence of orthostatic hypotension at the time of eligibility screening (orthostatic hypotension is defined as a drop in systolic blood pressure of 20mm Hg from sitting to standing, or drop in diastolic BP of 10 mm Hg from sitting to standing after 2-3 minutes of standing after being in a sitting position) * Anticipated inability to take oral medications on post-operative day #0 * Anticipated requirement for indwelling urinary catheter beyond post-operative day #2 * Non-English speaking * Pregnant or breast-feeding * Unwillingness to answer all 7 questions on the IPSS (International Prostate Symptom Score) survey * Lacking capacity to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Need for Any Intermittent Catheterization Postoperatively as a Binary Outcome | within 0-7 days after surgery | need for any intermittent catheterization after leaving the operating room or after initial indwelling urinary catheter (IUC) removal; subjects will be straight catheterized if the subject either 1) reports bladder discomfort, or 2) has a bladder scan for \>500milliliters; or 3) has a post-void residual volume \>500milliliters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Until First Spontaneous Void | within 0-7 days after surgery | time from IUC removal, last intermittent catheterization (if performed in the operating room or post-anesthesia care unit), or departure from the operating room (if no IUC placed intraoperatively) until first spontaneous void |
| Total Number of Intermittent Catheterizations Required Per Subject | within 0-7 days after surgery | total number of intermittent catheterizations required, as dictated by the institutional bladder management protocol |
| First Post-void Residual Urine Volume | within 0-7 days after surgery | The post-void residual (PVR) urine volume as measured by bedside hand-held bladder scanning immediately following the first spontaneous void |
| Need for Replacement of Indwelling Urinary Catheter as a Binary Outcome | within 0-7 days after surgery | Need for replacement of an IUC after surgery or after initial removal of an IUC that was placed at the time of surgery; replacement of IUC is dictated by the institutional bladder management protocol after requiring the use of straight catheterization for 24 hours |
| Urinary Tract Infection (UTI) | up to 30 days after surgery | Either a culture-positive UTI prior to discharge from the hospital or subject self-reported clinician-diagnosed UTI occurring within 30 days of surgery |
| Hospital Length of Stay in Days | up to 30 days after surgery | Collected after the participant is discharged from the hospital, total number of consecutive days (including day of surgery) until the participant is discharged from the hospital |
| Number of Participants Who Experienced Adverse Events | treatment day 1 (7 days before surgery) until 30 days after surgery | Adverse events, systematically collected. Summary results reported here, please refer to Adverse Events section of the results record for detailed reporting. |
| Discharge From Hospital With Indwelling Urinary Catheter | up to 30 days after surgery | Does the subject have a urinary catheter in place at the time of discharge from the hospital? This is a binary outcome measure of whether or not the subject is discharged from the hospital with an indwelling urinary catheter in place due to inadequate voiding function. |
Countries
United States
Participant flow
Recruitment details
Recruitment began in August 2015 and continued until Feb 2018. Subjects were recruited from surgery clinics at a single university hospital.
Pre-assignment details
Subjects were randomized within 1 month of their surgery date but \>7 days prior to surgery. 7 participants were not randomized for the following reasons: 4 subjects self-withdraw prior to randomization; 3 subjects had surgery date moved up to within the 7-day window before surgery
Participants by arm
| Arm | Count |
|---|---|
| Tamsulosin Tamsulosin: Tamsulosin 0.4mg capsule orally once daily, dosed 30 minutes after dinner or before bed, starting 7 days before surgery and continuing for 0-5 days postoperatively.
Outline of schedule:
* Day 1-7: tamsulosin 0.4mg in the evening
* Day 8: surgery; tamsulosin 0.4mg in the evening if the subject has not yet completed the bladder management protocol
* Day 9-14: tamsulosin 0.4mg in the evening until the subject either 1) completes the bladder management protocol (defined by two consecutive voids with post-void residual \<200mL), or 2) has an indwelling urinary catheter replaced, or 3) is discharged from the hospital, whichever occurs first. The minimum number of total doses is 7; the maximum number of total doses is 14. The 14th dose will be the final dose regardless of bladder function. | 76 |
| Placebo Placebo: Placebo capsule orally once daily, dosed 30 minutes after dinner or before bed, starting 7 days before surgery and continuing for 0-5 days postoperatively.
Outline of schedule:
* Day 1-7: placebo in the evening
* Day 8: surgery; placebo in the evening if the subject has not yet completed the bladder management protocol
* Day 9-14: placebo in the evening until the subject either 1) completes the bladder management protocol (defined by two consecutive voids with post-void residual \<200mL), or 2) has an indwelling urinary catheter replaced, or 3) is discharged from the hospital, whichever occurs first. The minimum number of total doses is 7; the maximum number of total doses is 14. The 14th dose will be the final dose regardless of bladder function. | 75 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | surgery cancelled | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Tamsulosin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 16 Participants | 21 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 54 Participants | 113 Participants |
| Age, Continuous | 52.7 years STANDARD_DEVIATION 15.8 | 54.5 years STANDARD_DEVIATION 14.4 | 53.6 years STANDARD_DEVIATION 15.1 |
| ASA Class ASA Class 1 | 3 Participants | 1 Participants | 4 Participants |
| ASA Class ASA Class 2 | 48 Participants | 55 Participants | 103 Participants |
| ASA Class ASA Class 3 | 19 Participants | 15 Participants | 34 Participants |
| Body Mass Index greater than or equal to 30, obese | 32 Participants | 29 Participants | 61 Participants |
| Body Mass Index less than 30, non-obese | 38 Participants | 42 Participants | 80 Participants |
| BPH | 3 Participants | 1 Participants | 4 Participants |
| CHF | 0 Participants | 1 Participants | 1 Participants |
| COPD | 3 Participants | 5 Participants | 8 Participants |
| Diabetes | 10 Participants | 7 Participants | 17 Participants |
| Epidural Epidural used | 25 Participants | 16 Participants | 41 Participants |
| Epidural No epidural | 45 Participants | 55 Participants | 100 Participants |
| History of Prior Urinary Retention | 10 Participants | 12 Participants | 22 Participants |
| Hypertension | 28 Participants | 30 Participants | 58 Participants |
| IBD | 20 Participants | 16 Participants | 36 Participants |
| IPSS High IPSS (Score >7) | 26 Participants | 26 Participants | 52 Participants |
| IPSS Low IPSS (Score <=7) | 44 Participants | 45 Participants | 89 Participants |
| Pelvic Surgery Non-pelvic Surgery | 30 Participants | 32 Participants | 62 Participants |
| Pelvic Surgery Pelvic Surgery | 40 Participants | 39 Participants | 79 Participants |
| Prior CVA | 3 Participants | 2 Participants | 5 Participants |
| Prior MI | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 73 Participants | 73 Participants | 146 Participants |
| Region of Enrollment United States | 76 participants | 75 participants | 151 participants |
| Sex: Female, Male Female | 34 Participants | 34 Participants | 68 Participants |
| Sex: Female, Male Male | 42 Participants | 41 Participants | 83 Participants |
| Smoker | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 76 | 0 / 75 |
| other Total, other adverse events | 10 / 76 | 8 / 75 |
| serious Total, serious adverse events | 3 / 76 | 5 / 75 |
Outcome results
Primary
Need for Any Intermittent Catheterization Postoperatively as a Binary Outcome
need for any intermittent catheterization after leaving the operating room or after initial indwelling urinary catheter (IUC) removal; subjects will be straight catheterized if the subject either 1) reports bladder discomfort, or 2) has a bladder scan for \>500milliliters; or 3) has a post-void residual volume \>500milliliters
Time frame: within 0-7 days after surgery
Population: This is an intent-to-treat analysis, including all subjects who were randomized and did not withdraw prior to the intended start date of their study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tamsulosin | Need for Any Intermittent Catheterization Postoperatively as a Binary Outcome | 18 Participants |
| Placebo | Need for Any Intermittent Catheterization Postoperatively as a Binary Outcome | 22 Participants |
Secondary
Discharge From Hospital With Indwelling Urinary Catheter
Does the subject have a urinary catheter in place at the time of discharge from the hospital? This is a binary outcome measure of whether or not the subject is discharged from the hospital with an indwelling urinary catheter in place due to inadequate voiding function.
Time frame: up to 30 days after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tamsulosin | Discharge From Hospital With Indwelling Urinary Catheter | 0 Participants |
| Placebo | Discharge From Hospital With Indwelling Urinary Catheter | 0 Participants |
Secondary
First Post-void Residual Urine Volume
The post-void residual (PVR) urine volume as measured by bedside hand-held bladder scanning immediately following the first spontaneous void
Time frame: within 0-7 days after surgery
Population: Only includes subjects who were NOT straight-catheterized AND there were 20 additional subjects for which PVR was not recorded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin | First Post-void Residual Urine Volume | 218 mL | Standard Deviation 167 |
| Placebo | First Post-void Residual Urine Volume | 154 mL | Standard Deviation 138 |
Secondary
Hospital Length of Stay in Days
Collected after the participant is discharged from the hospital, total number of consecutive days (including day of surgery) until the participant is discharged from the hospital
Time frame: up to 30 days after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin | Hospital Length of Stay in Days | 6.4 days | Standard Deviation 3.9 |
| Placebo | Hospital Length of Stay in Days | 6.0 days | Standard Deviation 3.3 |
Secondary
Need for Replacement of Indwelling Urinary Catheter as a Binary Outcome
Need for replacement of an IUC after surgery or after initial removal of an IUC that was placed at the time of surgery; replacement of IUC is dictated by the institutional bladder management protocol after requiring the use of straight catheterization for 24 hours
Time frame: within 0-7 days after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tamsulosin | Need for Replacement of Indwelling Urinary Catheter as a Binary Outcome | 5 Participants |
| Placebo | Need for Replacement of Indwelling Urinary Catheter as a Binary Outcome | 5 Participants |
Secondary
Number of Participants Who Experienced Adverse Events
Adverse events, systematically collected. Summary results reported here, please refer to Adverse Events section of the results record for detailed reporting.
Time frame: treatment day 1 (7 days before surgery) until 30 days after surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tamsulosin | Number of Participants Who Experienced Adverse Events | Serious Adverse Events | 3 Participants |
| Tamsulosin | Number of Participants Who Experienced Adverse Events | Other Adverse Events | 10 Participants |
| Placebo | Number of Participants Who Experienced Adverse Events | Serious Adverse Events | 5 Participants |
| Placebo | Number of Participants Who Experienced Adverse Events | Other Adverse Events | 8 Participants |
Secondary
Time Until First Spontaneous Void
time from IUC removal, last intermittent catheterization (if performed in the operating room or post-anesthesia care unit), or departure from the operating room (if no IUC placed intraoperatively) until first spontaneous void
Time frame: within 0-7 days after surgery
Population: Time to first spontaneous void was not collected as this is not relevant clinically to diagnosis of urinary retention, and our bladder management protocol prevents unbiased collection of this data point.
Secondary
Total Number of Intermittent Catheterizations Required Per Subject
total number of intermittent catheterizations required, as dictated by the institutional bladder management protocol
Time frame: within 0-7 days after surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tamsulosin | Total Number of Intermittent Catheterizations Required Per Subject | At least 1 catheterization | 18 Participants |
| Tamsulosin | Total Number of Intermittent Catheterizations Required Per Subject | At least 2 catheterizations | 8 Participants |
| Tamsulosin | Total Number of Intermittent Catheterizations Required Per Subject | greater than 2 catheterizations | 0 Participants |
| Placebo | Total Number of Intermittent Catheterizations Required Per Subject | At least 1 catheterization | 22 Participants |
| Placebo | Total Number of Intermittent Catheterizations Required Per Subject | At least 2 catheterizations | 10 Participants |
| Placebo | Total Number of Intermittent Catheterizations Required Per Subject | greater than 2 catheterizations | 5 Participants |
Secondary
Urinary Tract Infection (UTI)
Either a culture-positive UTI prior to discharge from the hospital or subject self-reported clinician-diagnosed UTI occurring within 30 days of surgery
Time frame: up to 30 days after surgery
Population: This participant did not have urinary retention; self-reported UTI, catheter was removed on post operative day #2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tamsulosin | Urinary Tract Infection (UTI) | 0 Participants |
| Placebo | Urinary Tract Infection (UTI) | 1 Participants |