Conditions: Postoperative Urinary Retention
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 90
Healthy volunteers: no

Brief summary:
Postoperative urinary retention is a frequent complication of spinal surgeries and impacts a large portion of this population which results in increased morbidity as a result of increased number of catheterizations, urinary tract infections (UTIs) and prolonged hospital stays. With the addition of Tamsulosin, the investigators would anticipate a reduction in the incidence and duration of postoperative urinary retention and therefore a reduction in morbidity related to treatment of urinary retention as well as shortened hospital stays.

Detailed description:
Decompressive laminectomy and spinal fusion procedures are among the most common neurosurgical procedures performed. Postoperative urinary retention (POUR) is a frequent complication of such surgeries and impacts a large proportion of this population resulting in multiple intermittent bladder catheterizations for bladder decompression, increased incidence of bacteremia, increased incidence of UTIs, and prolonged hospital stays. Use of a uroselective alpha-1-adrenergic receptor antagonist, such as tamsulosin, in the perioperative period (medication started five days prior to surgery and taken until hospital discharge) could reduce both the incidence and duration of postoperative urinary retention, resulting in shorter hospital stays and decreased healthcare costs.

Arms:
arm 1: Participants randomized to this arm will receive 0.4 mg/day tamsulosin hydrochloride from 5 days prior to the operation until hospital discharge. arm 2: Participants randomized to this arm will receive a daily placebo capsule matching the active study drug from 5 days prior to the operation until hospital discharge.

Interventions: intervention 1: Tamsulosin hydrochloride intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive 0.4 mg/day tamsulosin hydrochloride from 5 days prior to the operation until hospital discharge. intervention 2: The placebo capsule matching the active study drug will be given daily from 5 days prior to the operation until hospital discharge.

Protocol document:
Prot_SAP_000.pdf: 
 
 
The use of an uroselective Alpha-1-antagonist 
to reduce the incidence and duration of 
postoperative urinary retention following spine 
surgery 
 
NCT01568918 
 
February 01, 2012 


Research Proposal 
02-01-2012 
 
Title:   
 
The Use of a Uroselective Alpha-1-Adrenergic Receptor Antagonist to Reduce 
the Incidence of Postoperative Urinary Retention Following Spine Surgery 
 
Investigators:   
 
Terry K. Schiefer, M.D., Jeffrey T. Jacob, M.D., Steve Thalacker, R.N., Nathan 
Foster (Statistician), Shankar Srinivason (Office of Research and Regulatory 
Support), Fredric B. Meyer, M.D, William E. Krauss, M.D., Michelle J. Clarke, 
M.D. (Research Mentor), Mark A. Pichelmann, M.D. 
 
 
Abstract: 
 
Postoperative urinary retention (POUR) occurs in up to 38% of neurosurgical 
patients undergoing simple decompressive spine procedures, with even higher 
rates estimated after complex spinal procedures such as instrumented fusion. 
This can result in multiple intermittent catheterizations for bladder 
decompression, increased incidences of urinary tract infection, and prolonged 
hospital stays.  Previous non-neurosurgical series using nonspecific alpha-1-
adrenergic receptor antagonists have had some success in both the prevention 
and treatment of POUR.  However, according to a recent Cochrane review, the 
use of alpha-blockers for the prevention and treatment of POUR is under-
researched and there remains a need for well-designed clinical trials evaluating 
these drugs.  The current neurosurgical practice at Mayo Clinic has both the 
clinical volume and infrastructure to support a randomized controlled trial 
evaluating the use of tamsulosin, a uroselective alpha-1-adrenergic receptor 
antagonist, for the prevention and treatment of POUR.  If successful, this could 
not only result in decreased incidence and duration of POUR, but also in 
decreased hospital stays with an associated significant reduction in healthcare 
costs. 
 
 
Background: 
 
Postoperative urinary retention (POUR) is a common problem following 
neurosurgical procedures, specifically spine surgery.  Estimates of incidence of 
POUR range from 2 to 69% in various surgical series depending on the type of 
surgery, anesthetic technique, and the method used to evaluate urinary 
retention.1-8  In the only neurosurgical series specifically addressing the incidence 
of POUR, it was found to occur in 38% of patients undergoing simple 
decompressive spine surgeries with nearly an equal distribution between men 


(39.1%) and women (36.2%).9  The current mainstay of treatment for POUR is 
intermittent catheterization for bladder decompression until the retention resolves 
and the patient can void spontaneously.  This can result in increased rates of 
bacteremia and urinary tract infection (UTI).10,11  Furthermore, POUR has been 
shown to prolong hospital stay.9 
 
While many factors likely lead to the development of POUR, increased 
sympathetic outflow is thought to be central to its pathogenesis.12-14  The bladder 
and urethra are innervated by both the parasympathetic and sympathetic 
nervous systems.  While cholinergic receptors and beta-receptors are 
concentrated in the body of the bladder, alpha-adrenergic receptors are primarily 
localized in the bladder neck, proximal urethra, and prostate gland, with a relative 
high density of the 1A subtype.13,15-17  Stimulation of alpha-adrenergic receptors 
leads to smooth muscle contraction and increased tone.  Increased sympathetic 
discharge can lead to overactivation of these alpha-1-adrenergic receptors 
resulting in increased closing pressure and outflow resistance at the level of the 
bladder neck and proximal urethra, which can cause POUR.12,13  In the surgical 
patient there are a number of reasons for increased sympathetic discharge that 
can lead to POUR.  First, bladder distention alone can cause an increase in 
sympathetic motor activity,18 which is common in surgical patients who are given 
intravenous fluids perioperatively.  Second, there is an increase in sympathetic 
outflow as the body’s systemic response to the stress of surgery.  Finally, 
postoperative pain results in increased sympathetic firing.  
 
Multiple other risk factors have been associated with increased rates of urinary 
retention in the postoperative period.  These include increasing age,1-4,9,19,20 
longer duration of surgery,1,3,4,19-22 anesthetic technique,1,7,23 total intravenous 
fluid administered perioperatively,4,6,19 diabetes mellitus,3 post-operative 
analgesia,3,6,24 and previous history of voiding dysfunction.25  Unfortunately, 
many of these risk factors cannot be directly modified in the individual patient, 
such as age, operative time, the use of general anesthesia, or limiting 
intravenous fluid administration without potentially putting patients at risk.  
 
Two main intervention strategies have been investigated to overcome urinary 
retention by facilitating bladder emptying.  The first is to augment contraction of 
the detrusor muscle by stimulation of postsynaptic parasympathetic receptors in 
the wall of the bladder using anticholinesterases.  This strategy has been met 
with limited success in most studies and has been largely abandoned.13,26-28 
Bedside uroflowmetry studies in patients experiencing retention have shown that 
POUR occurs despite active contraction of the detrusor muscle, implicating outlet 
obstruction as the more important mechanism.29  This has led to the second 
strategy, which is to relieve obstruction at the bladder outlet and thereby facilitate 
bladder emptying.  As discussed above, increased sympathetic outflow during 
the perioperative and postoperative period can result in increased muscle tone at 
the bladder outlet due to activation of alpha-1-adrenergic receptors. Thus, 
blockade of these alpha-1-adrenergic receptors should result in relaxation of 


these structures and augment bladder emptying, thereby reducing both the 
incidence and duration of POUR.   
 
Previous studies have shown benefit in using nonspecific alpha-1-adrenergic 
receptor antagonists (phenoxybenzamine, alfuzosin, and prazosin) in the 
perioperative period to reduce the incidence and duration of urinary retention 
postoperatively.  Several non-neurosurgical series, have demonstrated reduced 
incidence of POUR, fewer required catheterizations, and a decrease in UTIs in 
patients treated with alpha-1-adrenergic receptor blockade.12,13,30-36  Two studies 
did not show a benefit of alpha-adrenergic receptor blockade for POUR.  The first 
study randomized hemorrhoidectomy patients into treatment groups consisting of 
prazosin and placebo.37  No difference was found in the incidence of urinary 
retention.  However, a large limitation of this study was that all patients 
underwent spinal anesthesia, an important independent risk factor for urinary 
retention that may have prolonged effects on the ability of the detrusor muscle to 
contract due to blockade of the parasympathetic innervation to the muscle.1,38  
Additionally, only 46 total patients were randomized raising questions of 
adequate sample size.  The second negative study compared the use of 
alfuzosin to a combination of carbachol/diazepam and placebo.39  In this study, 
subjects were not pretreated with alfuzosin and were given the medications only 
after having an inability to void six hours or more after surgery.  This may have 
resulted in over-distention of the bladder and detrusor atony, which is a known 
complication of excess intravenous fluid administration resulting in retention.40  
Furthermore, there may have been inadequate time for the drug to reach 
therapeutic steady state concentrations and thus underestimated the potential 
benefit of the medication.   
 
Despite some success with nonspecific alpha-1-adrenergic receptor antagonists 
in the prevention and treatment of POUR, it remains a common surgical 
complication and perioperative alpha blockade has not yet become the standard 
of care for high-risk patients or procedures.  In a recent Cochrane review 
analyzing drug treatment for POUR, the following statement was made:  “The 
potential of drugs in treating post-operative urinary retention should be further 
investigated, including alpha blockers, which appear to have been under-
researched considering their theoretical usefulness.  There remains a need for 
well-designed and adequately powered trials to assess the effectiveness of drugs 
for the treatment of post-operative urinary retention, a common surgical 
complication.”41  To date, no studies have been reported using newer 
uroselective alpha-1-adrenergic receptor antagonists, such as tamsulosin, in 
postoperative patients.  Based on prior reports of success with nonspecific alpha-
1-antagonists, it is hypothesized that treatment with tamsulosin will result in even 
greater benefit towards reducing urinary retention with fewer side effects due to 
its uroselective nature.  Prior studies have shown reduced incidences of 
dizziness, hypotension, and dry mouth with tamsulosin when compared to 
nonspecific alpha-adrenergic receptor antagonists.42 
 


Tamsulosin has been approved for use in treating the signs and symptoms of 
benign prostatic hyperplasia in males.  Its mechanism of action is through 
blockade of alpha-1-adrenoreceptors at the bladder neck and prostatic urethra 
resulting in improvement of bladder outlet obstruction and reduction of maximum 
voiding detrusor pressure.  As opposed to nonspecific alpha-1-adregnergic 
antagonists, tamsulosin has a higher affinity for the alpha-1A adrenergic receptor 
subtype, which comprises the majority of alpha-receptors in the lower urinary 
tract, compared to the alpha-1B subtype primarily located in vascular smooth 
muscle.  It is metabolized in the liver and excreted primarily through the kidney.  
Dosing adjustments are recommended only in patients with severe liver disease 
or end-stage renal failure.  Time to maximum concentration is 4-8 hours after 
administration in the fasting state, and patients reach steady state concentrations 
after approximately 5 days of therapy.  Significant adverse events have been 
reported rarely.  These include signs and symptoms of orthostasis (0.2%), 
priapism (rare, <1 in 50,000), and intraoperative floppy iris syndrome (rare 
reports during cataract surgery).16  While currently only FDA approved for use in 
males, studies have also demonstrated efficacy in treating urinary retention and 
voiding difficulty in females as well.43-45   
 
 
Rationale: 
 
Decompressive laminectomy and spinal fusion procedures are among the most 
common neurosurgical procedures performed.  POUR is a frequent complication 
of such surgeries and impacts a large proportion of this population resulting in 
multiple intermittent bladder catheterizations for bladder decompression, 
increased incidence of bacteremia, increased incidence of UTIs, and prolonged 
hospital stays.  Use of a uroselective alpha-1-adrenergic receptor antagonist, 
such as tamsulosin, in the perioperative period (medication started five days prior 
to surgery and taken until hospital discharge) could reduce both the incidence 
and duration of postoperative urinary retention, resulting in shorter hospital stays 
and decreased healthcare costs. 
 
Hypothesis 1:  Tamsulosin started five days preoperatively and taken until 
hospital discharge will significantly decrease the incidence of postoperative 
urinary retention among neurosurgical patients undergoing decompressive 
laminectomy and/or spinal fusion procedures compared to placebo.  (Primary 
Hypothesis) 
 
Hypothesis 2:  Tamsulosin started five days preoperatively and taken until 
hospital discharge will significantly decrease the duration of postoperative 
urinary retention among neurosurgical patients undergoing decompressive 
laminectomy and/or spinal fusion procedures who experience this surgical 
complication compared to placebo.  (Secondary Hypothesis) 
 


Hypothesis 3:  Tamsulosin started five days preoperatively and taken until 
hospital discharge will significantly decrease the length of hospital stay among 
neurosurgical patients undergoing decompressive laminectomy and/or spinal 
fusion procedures compared to placebo.  (Secondary Hypothesis) 
 
Specific Aims: 
 
1) To determine if the use of a uroselective alpha-1-adrenergic receptor 
antagonist during the perioperative period reduces the incidence and 
duration of POUR in neurosurgical patients undergoing decompressive 
laminectomy and/or spinal fusion. 
2) To determine if reduced incidence and duration of POUR in this patient 
population will result in decreased length of hospital stay. 
 
Experimental Design: 
 
The study design will be a prospective randomized controlled double-blinded 
clinical trial comparing a uroselective alpha-1-adrenergic receptor antagonist 
(tamsulosin, 0.4mg per day) with placebo in neurosurgical patients undergoing 
decompressive cervical or lumbar laminectomy and/or spinal fusion.  The study 
population will consist of all neurosurgical patients undergoing decompressive 
laminectomy and/or spinal fusion at Mayo Clinic Rochester from the time of study 
initiation (early 2012) that meet inclusionary criteria, do not meet any 
exclusionary criteria, and give consent to enter the study.  Patients that enter the 
study will be randomized to receive tamsulosin (treatment group) or placebo 
(control group).  The primary outcome variable will be the incidence of POUR.  
Secondary outcome variables of interest will include duration of POUR and 
length of hospital stay.  Additional variables (demographic factors, number of 
catheterizations, incidence of UTI, etc.) will also be collected for comparison of 
the homogeneity of the two groups with respect to known confounding factors 
and to analyze other outcomes of interest.  Data on all outcome variables will be 
collected by the time of hospital discharge.  Therefore, this study will require 
minimum follow up time and it is estimated that patients will actively be 
participating in the study for an average of 8-12 days.  Patients and providers will 
be blinded to treatment assignment for the duration of the study. 
 
Based on sample size calculations (see Analysis of the Data section below), it is 
estimated that 175 patients will need to be recruited into each group.  The 
Department of Neurological Surgery at Mayo Clinic Rochester performs 
approximately 4000 major neurosurgical procedures per year, of which 
approximately half are spinal procedures.  Of those, approximately 1000 cases 
should meet the surgical criteria for this study.  Thus, it is estimated that a one-
year time frame will provide sufficient time to recruit the necessary 350 patients 
and perform the study.   
 
 


Methods: 
 
Subject Recruitment and Retention: 
 
Study subjects will be recruited through referral for surgical consultation in the 
neurosurgery outpatient clinic at Mayo Clinic Rochester.  Individual surgeons will 
determine whether a surgery is indicated in particular patients.  After the decision 
has been made to proceed with surgery, the patient will be interviewed for 
eligibility into the study, consented, and enrolled by the respective 
neurosurgeon’s physician extender (R.N. or N.P.).  Eligibility criteria are included 
in Table 1 and will be reviewed with each patient during the preoperative visit 
addressing the eligibility requirements for entry into the study.  Patients 
undergoing simple spinal procedures (discectomy and foraminotomy procedures) 
that typically have next day hospital discharges and low incidences of POUR will 
be excluded from the study.  It is not anticipated that subject retention will 
present a major challenge because the duration of study follow up is limited to 
the duration of the postoperative hospital stay.  It is estimated that subjects will 
be actively participating in the study for approximately 8-12 days in most cases.  
Subject recruitment will continue until at least 175 subjects have been recruited 
into both the treatment and control groups and have completed the study.  An 
interim analysis will be performed with unblinded data from the research 
pharmacy when 75 or more patients have completed participation. 
 
Table 1: 
Inclusion Criteria 
Exclusion Criteria 
≥ 35 years (Males & Females) 
< 35 years 
Cervical Laminectomy  
Cervical Posterior Fusion 
Cervical Anterior/Posterior Fusion 
Lumbar Laminectomy 
Lumbar Posterolateral Fusion 
Lumbar Interbody Fusion 
Cervical Anterior Discectomy and Fusion 
Cervical Anterior Corpectomy 
Cervical Posterior Discectomy 
Cervical Foraminotomy 
Lumbar Discectomy (METRx or Open) 
Lumbar Foraminotomy 
Lumbar Anterior Fusion 
Myelopathy with bladder dysfunction 
Patients currently taking an alpha-
antagonist# 
Patients with history of allergy or sensitivity 
to tamsulosin or other alpha-antagonist 
History of prostatectomy or urologic 
surgery involving the bladder or urethra 
Severe liver disease or end-stage renal 
disease 


Patients taking strong inhibitors of 
CYP3A4* 
Mental disability or prisoner 
 
#The following drugs are alpha antagonists:  alfuzosin, doxazosin, prazosin, 
terazosin, tamsulosin, and phenoxybenzamine.46,47 
 
*The following drugs are strong inhibitors of CYP3A4:  ketoconazole, 
itraconazole, clarithromycin, ritonavir, indinavir/ritonavir, lopinavir/ritonavir, and 
conivaptan.48 
 
 
Randomization: 
 
A consecutive sample of subjects that meet eligibility requirements and give 
informed consent will be randomized to two study groups via a randomization 
number generated from a random numbers table.  Based on their randomization 
number patients will be given a prescription (for either tamsulosin or a like-
appearing placebo) from the Mayo pharmacy at least one week prior to the date 
of surgery.  The pharmacy will record which group the patient has been assigned 
to in a central pharmacy database.  This database will then be used in the 
perioperative and postoperative period to maintain the patient’s drug designation 
and administration while in the hospital.  The randomization will be blinded to 
both the treating physician’s team and the patient until the end of the study and 
data analysis is undertaken.   
 
Drug Administration: 
 
In order to achieve full steady state concentrations of the drug by the time of 
surgery, patients will be instructed to take the assigned drug for 5 days prior to 
surgery, as well as the morning of surgery. Thus, patients will be given 6 pills of 
the study medication or the like-appearing placebo at a preoperative clinic visit.  
On the morning of surgery patients will be admitted to Saint Marys Hospital as 
morning admissions and proceed to surgery that day based on the surgical 
schedule.  Data on medication compliance will be collected and recorded at that 
time.  Patients will continue taking tamsulosin 0.4mg or like-appearing placebo 
provided by the Mayo Pharmacy beginning on post-operative day one and 
continuing every day during their postoperative hospital course until the time of 
discharge.   At that time the primary treating team will write an order to 
discontinue the study medication.  Because each patient will be at therapeutic 
steady state concentrations of the drug by the time of surgery, shorter hospital 
stays should not underestimate the potential treatment benefit of this medication.  
Standard postoperative orders for patients undergoing decompressive cervical or 
lumbar laminectomy and/or spinal fusion have been in place for neurosurgical 
patients and will continue to be used during this study (postoperative order set 


MC1156-404).  The cost of the study medication will be covered by the study and 
patients will not be charged.   
 
Pre-operative Post Void Residual Urine Volume: 
 
A pre-operative post void residual (PVR) volume of urine will be obtained on all 
enrolled patients at their pre-operative clinic visit prior to beginning their drug 
assignment (tamsulosin or placebo).  This will be measured using the same 
technique as will be performed during the post-operative period (see Outcome 
Measures below).  This baseline PVR will help determine efficacy of the study 
drug as outcomes are measured.  The residual will be done by a member of the 
study staff and patients will not be charged.   
 
Outcome Measures: 
 
The primary outcome measure will be the incidence of POUR.  POUR will be 
defined as any of the following: 
 
1) Estimated post-void residual (PVR) volume of urine greater than or equal 
to 300 mL. 
2) Estimated retention urine volume of greater than or equal to 500 mL in 
patients unable to void.   
3) Patients experiencing discomfort or distension and unable to void with 
lesser residual urine volume than 500 ml  
 
Neurosurgical nursing staff currently follow the institutional Urinary Retention 
Protocol (MC1156-214rev0610.) This protocol includes an algorithm for both 
diagnosing postoperative urinary retention and its treatment.  This protocol has 
been in use for all postoperative spine patients since 2003 and the most current 
version is based on the above definition of urinary retention.  All residual volume 
of urine measurements will be made with a standard bladder scanner instrument 
that is currently in use on the neurosurgery wards. Presence or absence of 
urinary retention will be recorded in the electronic medical record (EMR) for later 
data retrieval and analysis.    
 
Secondary outcome variables include duration of POUR among those patients in 
which it occurs, number of intermittent catheterizations in those with urinary 
retention, incidence of UTI, and duration of hospital stay.  Measurement of the 
duration of POUR will closely coincide with the methods for recording incidence 
of POUR as discussed above.  The decision to use and the time of removal of 
indwelling urinary catheters will be left to the discretion of the primary 
neurosurgical team.  Time of indwelling catheter removal after surgery will serve 
as time zero for beginning calculation of postoperative urinary retention duration 
if the patient later requires in and out straight catheterization.  For patients 
without an indwelling catheter, the time patients leave the operating room will 
serve as time zero.  Per the Urinary Retention Protocol (MC1156-214rev0610), 


patients found to be experiencing POUR will be ordered to have a straight in and 
out catheterization performed by a member of the catheterization team after 
failure of noninvasive measures (e.g. trigger techniques, bladder massage, 
application of warmth, relaxed environment, privacy, ambulation) by the attending 
nursing staff member.  Urinary retention will be considered resolved after two 
consecutive post-void residual urine scans have demonstrated less than 300 ml 
residual urine volume in a patient spontaneously voiding.  The number of 
intermittent catheterizations is recorded in the EMR in accordance with the 
standardized protocol.  
 
Patients suspicious of having a UTI based on signs and symptoms of urinary 
frequency, urgency, burning or pain will have a urine sample (via catheterization 
or spontaneous void) sent for routine urinalysis, gram stain, and 
culture/sensitivity by the nursing staff member responsible for the patient or the 
primary neurosurgical team, per instructions documented on the Urinary 
Retention Protocol (MC1156-214rev0610).  Positive UTIs will be defined as 
positive gram stain in the presence of signs or symptoms of UTI, urine white 
blood cell count elevation, and positive culture of >104 cfu/ml.  Patients will be 
treated with the appropriate antibiotic based on culture sensitivity.   
 
Length of hospital stay will be recorded for all patients following the surgical 
procedure with the day after surgery defined as postoperative day one.  The 
medical record will be reviewed following discharge to determine if hospital 
discharge date was dependent on POUR or other reason (e.g. uncontrollable 
pain, mobility requiring physical therapy or inpatient rehabilitation, or other 
medical complications delaying discharge).   
 
In addition to the primary and secondary outcome measures, baseline 
characteristics will be collected on all patients via the medical record including 
age, height and weight, past history of postoperative urinary retention or 
diagnosis of benign prostatic hyperplasia (not on treatment), length and type of 
surgery, estimated blood loss during surgery, total intravenous fluids 
administered perioperatively, time to oral analgesic use (in hours), total analgesic 
use during the postoperative period, time to first postoperative mobility (in hours), 
and any adverse events thought to be related to administration of the study 
medication. These variables will be used as baseline comparisons between the 
two groups to ensure homogeny and be used in statistical adjustment if 
differences between the groups are significant after randomization. 
 
Unanticipated events: 
 
There is the potential for patients to experience urinary retention as outpatients 
after inpatient urinary retention has resolved.  This is quite unusual to occur after 
urinary retention has resolved as defined above and may indicate the patient 
needs further investigation by a urologic surgeon.  Patients will be counseled by 
nursing staff prior to dismissal regarding the signs and symptoms of urinary 


retention and directed to seek medical attention with appropriate urology referral 
should the treating physician deem this is appropriate.   
 
Patients experiencing prolonged postoperative urinary retention (> 5 days) will be 
seen by the urology consult service for recommendations regarding further 
investigation and treatment.  The study group designation may be broken at this 
point to determine which group the patient is in regarding treatment medication if 
deemed necessary by the urology consult service to guide further treatment. 
 
Patients experiencing severe adverse events such as profound hypotension, 
arrhythmia, or allergic reaction will be evaluated by the primary neurosurgical 
team with appropriate intervention or consultation as deemed necessary. 
 
Quality Control: 
 
An operations manual will be prepared prior to initiation of the study and will be 
distributed as necessary to all staff involved.  Treating neurosurgeons and their 
respective physician extenders will be instructed on the study goals, risks, and 
expected outcomes, as well as the identification and recruitment of eligible 
patients to the study, including obtaining consent.  Residents and staff 
neurosurgeons responsible for inpatients following surgery will be informed of the 
study goals and methodology with special emphasis on reporting adverse events 
and the appropriate means to resolution in conjunction with the principal 
investigator (PI)/co-principal investigator (Co-PI) and co-investigators prior to the 
study starting.  Any questions or concerns arising in relation to the study will be 
forwarded to the primary investigator as these concerns arise. 
 
Nursing staff responsible for patients in the postoperative period will continue to 
use the standard postoperative order sets for surgical patients undergoing spine 
procedures as well as the urinary retention protocol.  An informational meeting 
will be arranged with the head nurses of the neurosurgical wards where 
postoperative patients will reside following surgery to discuss the goals, rationale, 
and methods particular to the study.  Contact information for reporting adverse 
events or questions regarding study implementation will be provided before the 
study begins.  
 
Any and all questions will be forwarded to the PI/Co-PI, or study co-investigators 
should the PI/Co-PI be unavailable, in a timely manner with multiple sources of 
contact available (i.e. pager, telephone numbers, e-mail addresses). 
 
The Mayo Clinic Pharmacy will provide both the study drug (tamsulosin) and a 
like-appearing placebo.  A labeling system to track patient assignments, but that 
blinds study subjects and investigators, will be utilized.  
 
Data will be collected prospectively in an ongoing fashion for the duration of the 
study by investigators blinded to patient treatment group.  Because the vast 


majority of data will be collected from the EMR in a prospective fashion while the 
patient is either in the hospital or shortly thereafter, it is not anticipated that there 
will be much missing data.  
 
All statistical analysis and report of results will be done in a confidential manner 
and no information linking individual patients with data from the study will be 
shared outside of the study.  Every effort will be made to keep this data 
anonymous once it has been collected. 
 
Analysis of the Data: 
 
Baseline characteristics will be compared between the two study groups using a 
chi-squared or Fisher’s Exact Test for categorical variables and multiple two 
sample t-tests for continuous variables.  The primary outcome variable, incidence 
of POUR, as well as other categorical variables, such as incidence of UTI, will be 
analyzed using a chi-squared test or Fisher’s Exact Test.  Duration of POUR will 
be compared using a two sample non-paired t-test comparing means.  An 
appropriate nonparametric test (e.g. Wilcoxon Rank Sum) will be used for non-
normal appearing data as can be anticipated for length of hospital stay.  
Differences in the groups with respect to baseline variables will be used to 
construct a multiple linear regression model to control for potential confounding 
factors if necessary.  Intention to treat analysis will be used for all comparisons 
between groups. 
 
The primary outcome measure of incidence of POUR was used to calculate 
sample size.  Data gathered from multiple series suggests that postoperative 
urinary retention occurs in 2-69% of patients undergoing a variety of surgical 
procedures, with 38% occurring in neurosurgical patients undergoing simple 
decompressive spinal procedures.  Using 20% (P2=0.20) as a conservative 
estimate of incidence, an effect size of 10% for the primary outcome variable 
(P1=0.10) would be clinically meaningful.  Thus, P2-P1 = 0.10.  Because 
incidence of urinary retention is a binary categorical variable, a chi-squared test 
can be used to compare groups.  Based on a type I error rate of 0.05 (α), a type 
II error rate of 0.20 (β), and power of 0.80 the estimated sample sizes needed for 
each group are as follows.  For a one sided type 1 error, there would need to be 
175 subjects in each group.  For a two-sided type 1 error there would need to be 
219 subjects in each group.  A one-sided test of significance is reasonable in this 
study because an increase in incidence of POUR experienced in the tamsulosin 
treated group is not anticipated and would not add additional useful information in 
terms of using tamsulosin for POUR.  Thus, a reasonable estimate for sample 
size is 175 subjects in both the treatment and control groups.  Furthermore, with 
175 patients per arm, there would be 87% power to detect a 1 day difference in 
the duration of urinary retention and duration of hospital stay with a 1-sided 
significance level of 0.05 (this assumes an effect size for this secondary outcome 
variable of 0.30 [1 day difference in means/pooled standard deviation estimate of 
3.33]).   


 
 
 
Role in Project: 
 
Terry K. Schiefer:  Co-Principalinvestigator for the study, responsible for study 
design, study implementation, data collection, reporting of adverse events, and 
manuscript preparation. 
 
Jeffrey T. Jacob:  Co-investigator responsible for assisting in study 
implementation, data collection, and manuscript preparation. 
 
Steve Thalacker:  Co-investigator responsible for IRB application, Informed 
Consent form, and pharmacy liaison. 
 
Nathan Foster:  Statistician responsible for overseeing statistics performed by the 
co-PI as part of the CTSA BERD program. 
 
Shankar Srinivason:  Member of the Office of Research and Regulatory support 
who will be assisting with the Investigational New Drug application and 
corresponding with the FDA.   
 
Frederic B. Meyer:  Co-investigator responsible for assisting with study design, 
study implementation, and manuscript preparation 
 
William E. Krauss:  Co-investigator responsible for assisting with study design, 
study implementation, and manuscript preparation 
 
Michelle J. Clarke:  Principal Investigator responsible for mentoring the primary 
investigator, serving as the liaison between the FDA for the Investigational New 
Drug application, assisting with study design, study implementation, and 
manuscript preparation 
 
Mark A. Pichelmann:  Co-Principal Investigator responsible for mentoring the 
primary investigator, assisting with study design, study implementation, and 
manuscript preparation. 
 
 
Significance: 
 
POUR is a common problem following spine surgery in otherwise healthy 
patients.  It results in multiple intermittent catheterizations for bladder 
decompression, increased incidences of bacteremia and UTIs, and prolonged 
hospital stay.  This study will provide insight into the effectiveness of alpha-1-
adrenoreceptor blockade at the bladder neck to reduce the incidence and 
duration of POUR in patients undergoing neurosurgical spine procedures.  If 


effective, this treatment has the potential to change practice patterns in both 
neurosurgery and orthopedic spine practices throughout not only the United 
States, but also throughout the world.  Perioperative use of tamsulosin, or 
another uroselective alpha-1-adrenoreceptor blocker, could become the standard 
of care.  This could be especially important in the current economic environment 
where healthcare costs are closely scrutinized, as a reduction in both the 
incidence and duration of POUR could lead to shorter hospital stays and a 
significant decrease in healthcare spending.  Furthermore, the results of this 
study could potentially be applied to other types of surgeries with high rates of 
POUR and may be the platform for starting many other clinical trials.   
 
Human Studies Aspects: 
 
Tamsulosin is currently only FDA approved for use in the treatment of BPH in 
men.  With the help of the Office of Research and Regulatory Support (ORSS), 
an Investigational New Drug (IND) application was sent to the Food & Drug 
Administration (FDA) in December 2011 to use tamsulosin in this study in both 
men and women and was approved.   
 
Adverse Events: 
 
Studies using nonspecific alpha-1-adrenergic receptor blockade have shown 
benefit in reducing POUR with minimal adverse effects.12,13,30-37,39  Tamsulosin is 
regarded as being safer with respect to cardiovascular side effects than earlier 
generation alpha-1-antagonists due to its uroselective nature.45,49,50  The 
potential benefit of reduced incidence and duration of POUR, reduced morbidity 
associated with repeat intermittent catheterizations, reduced incidence of UTI, 
and reduced hospital length of stay outweigh the risks associated with 
administration of this medication.   
 
The primary risk to human subjects taking tamsulosin in this study is postural or 
orthostatic hypotension, estimated to occur in 0.2% of patients taking the 0.4 mg 
daily dose of the drug.  All patients will be regularly monitored with respect to 
blood pressure, heart rate, and rhythm according to existing standard 
postoperative procedures in place on the neurosurgical wards.  Per the 
postoperative neurosurgery protocol, all patients are ambulated with the 
assistance of nursing staff until they are deemed safe for independent 
ambulation.  Abnormal ejaculation was reported in 8.4% of patients taking the 0.4 
mg daily dose.  This risk should be minimal in the study given the short duration 
of time taking the study medication and decreased likelihood of sexual activity in 
the immediate postoperative period.  There have been some reports of 
intraoperative floppy iris syndrome during cataract surgery while taking 
tamsulosin.  Patients will be advised to avoid cataract surgery during the short 
time they are on the study medication.  Allergic type reactions have been 
reported rarely.  Patients will be informed as to the signs and symptoms of 


allergic reactions.  Priapism has also been reported as a rare risk (less than 1 in 
50,000).  Male patients will be informed about the seriousness of this condition.   
 
Other adverse reactions include headache, dizziness, rhinitis, infection, asthenia, 
back pain, diarrhea, pharyngitis, chest pain, cough increased, somnolence, 
nausea, sinusitis, insomnia, libido decreased, tooth disorder, and blurred vision.  
Postmarketing experiences have also shown infrequent reports of dyspnea, 
palpitations, hypotension, atrial fibrillation, arrhythmia, tachycardia, skin 
desquamation including reports of Stevens-Johnson syndrome, constipation, and 
vomiting.  All risks are taken directly from the official FDA drug information 
sheet.16 
 
Patients experiencing possible severe side effects from this medication will be 
instructed to contact the primary neurosurgical team prior to hospitalization.  
During hospitalization, any patients experiencing such effects will be immediately 
evaluated by the neurosurgical team with appropriate intervention or consultation 
as deemed necessary.  The PI or Co-PI will be informed of any serious adverse 
events thought to be related to medication administration and appropriate steps 
will be taken to determine whether the adverse event was related to the 
medication under investigation or other patient medication/condition (e.g. narcotic 
analgesics, other cardiovascular medication, or dehydration).  The decision to 
stop the study medication will be determined by the primary neurosurgical team 
responsible for the patient in collaboration with the PI/Co-PI after the seriousness 
of the event is taken into consideration.  All serious adverse events will be 
reported to the Mayo IRB within 24 hours of the event taking place, and to the 
FDA if necessary.  All major and minor adverse effects of the study medication 
(tamsulosin or placebo) will be recorded in the medical record and used for data 
analysis. 
 
Inclusion of Women, Minorities, and Children:  
 
Women will be included in this study.  Minorities will be included in the study in 
the same proportion as they present to the outpatient neurosurgery clinic.  
Mentally disabled patients, prisoners, and children will be excluded from the 
study. 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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