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Reduction of Bladder Injection Pain With Belladonna Opiate Suppository (ROBIN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02600715
Recruitment Status : Completed
First Posted : November 9, 2015
Results First Posted : September 20, 2018
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
Edgar LeClaire, MD, University of Kansas Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Overactive Bladder
Urinary Urge Incontinence
Urinary Bladder, Neurogenic
Painful Bladder Syndrome
Interventions Drug: Onabotulinumtoxin A (BoNT)
Drug: belladonna
Drug: Morphine
Drug: Placebo
Drug: Active B&O suppository of belladonna
Enrollment 26
Recruitment Details Recruitment began December 1, 2015 at a private urogynecology clinic. There were 32 patients that were assessed for eligibility. Four patients were excluded: three patients did not meet inclusion criteria (did not proceed with in-office treatment) and one patient declined to participate due to wanting the active suppository.
Pre-assignment Details

28 patients consented to participate in the study. Two patients withdrew consent to participate and did not end up participating: one patient's medication resumed efficacy, and one patient withdrew regarding possible use of narcotics and concern due to a a previous narcotic addition.

Thus, only 26 patients are considered enrolled in this study.

Arm/Group Title Active Belladonna & Opiate (B&O) Suppository Placebo Suppository
Hide Arm/Group Description

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

Period Title: Overall Study
Started 13 13
Allocated to Randomization 13 13
Received Treatment and Suppository 13 13
Completed 2-week Follow-up Appointment 13 12
Completed [1] 13 13
Not Completed 0 0
[1]
Included in final analysis
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

Total of all reporting groups
Overall Number of Baseline Participants 13 13 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 13 participants 26 participants
73.62  (10.25) 65.54  (10.22) 69.58  (10.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Female
13
 100.0%
13
 100.0%
26
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
13
 100.0%
13
 100.0%
26
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Body mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 13 participants 13 participants 26 participants
35.45  (11.34) 34.19  (6.33) 34.82  (9.02)
Vaginal parity   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Pregnancies
Number Analyzed 13 participants 13 participants 26 participants
2
(2 to 3)
3
(1 to 3)
2
(2 to 3)
[1]
Measure Description:

Vaginal parity is the number of pregnancies that the patient had, that was carried to greater 20 weeks.

Zero indicates that the patient did not have any pregnancies beyond 20 weeks (nulliparous).

Current smoker  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
1
   7.7%
1
   7.7%
2
   7.7%
Menopausal  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
13
 100.0%
12
  92.3%
25
  96.2%
Estrogen use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Vaginal estrogen
4
  30.8%
7
  53.8%
11
  42.3%
Oral estrogen
2
  15.4%
1
   7.7%
3
  11.5%
Gynecologic disorders/diagnoses  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Vulvovaginal atrophy
7
  53.8%
7
  53.8%
14
  53.8%
Constipation
1
   7.7%
2
  15.4%
3
  11.5%
Chronic cystitis
3
  23.1%
2
  15.4%
5
  19.2%
Cystocele
0
   0.0%
3
  23.1%
3
  11.5%
Vaginal vault prolapse
1
   7.7%
2
  15.4%
3
  11.5%
Uterine prolapse
0
   0.0%
0
   0.0%
0
   0.0%
Rectocele
0
   0.0%
1
   7.7%
1
   3.8%
Medication use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Steroid medication
1
   7.7%
0
   0.0%
1
   3.8%
Narcotic medication
1
   7.7%
1
   7.7%
2
   7.7%
Diuretic medication
1
   7.7%
4
  30.8%
5
  19.2%
Surgical history  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Hysterectomy
10
  76.9%
10
  76.9%
20
  76.9%
Bilateral salpingo-oophorectomy (BSO)
6
  46.2%
7
  53.8%
13
  50.0%
Prolapse surgery with mesh
0
   0.0%
1
   7.7%
1
   3.8%
Prolapse surgery without mesh
2
  15.4%
3
  23.1%
5
  19.2%
Previous sling procedure
3
  23.1%
3
  23.1%
6
  23.1%
Laparotomy
5
  38.5%
5
  38.5%
10
  38.5%
Back or spinal surgery
3
  23.1%
2
  15.4%
5
  19.2%
Medication use in Last 24 Hours   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Selective serotonin reuptake inhibitors (SSRIs)
7
  53.8%
0
   0.0%
7
  26.9%
Nonsteroidal anti-inflammatory drugs (NSAIDs)
5
  38.5%
6
  46.2%
11
  42.3%
Sedative medication
1
   7.7%
5
  38.5%
6
  23.1%
Neuromodulator medication
1
   7.7%
1
   7.7%
2
   7.7%
Opioid medication
2
  15.4%
1
   7.7%
3
  11.5%
[1]
Measure Description: Participant medication use in last 24 hours prior to intravesical onabotulinum toxin A injection
1.Primary Outcome
Title Change in Bladder Injection Pain
Hide Description The primary outcome will be calculated difference in numeric rating scale (NRS) pain score prior to procedure and midway through procedure. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain). Measure will be reported as the intraoperative pain score minus the preoperative pain score.
Time Frame Baseline and intraoperative
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

26 participants
Overall Number of Participants Analyzed 13 13 26
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
5
(2 to 6)
4
(3 to 5)
5
(2 to 6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active B&O Suppository of Belladonna, Placebo Suppository
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Test for differences in continuous variables.
Statistical Test of Hypothesis P-Value 0.94
Comments Two-sided alpha of 0.05 was used to determine statistical significance.
Method Kruskal-Wallis
Comments [Not Specified]
2.Secondary Outcome
Title Pre-analgesia Pain Score
Hide Description Measured using NRS. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain).
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

26 participants
Overall Number of Participants Analyzed 13 13 26
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
3.Secondary Outcome
Title Post-operative Pain Score
Hide Description Measured using NRS. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain).
Time Frame Postoperative (within 10 minutes of the end of the BoNT procedure)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

26 participants
Overall Number of Participants Analyzed 13 13 26
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
2
(0 to 5)
3
(1 to 7)
2
(1 to 5)
4.Secondary Outcome
Title Number of Participants Declining to Complete Procedure Due to Pain Intolerance
Hide Description Number of patients that decline to proceed with entire procedure (20 injections) due to pain or discomfort.
Time Frame Intraoperative
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

26 participants
Overall Number of Participants Analyzed 13 13 26
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Postoperative Voiding Trial Results
Hide Description Distribution of patients with postoperative volume in ml of post-void residual urine obtained via catheter greater than 200ml.
Time Frame Postoperative (before leaving the clinic, within 3 hours of the end of the BoNT procedure)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

26 participants
Overall Number of Participants Analyzed 13 13 26
Measure Type: Count of Participants
Unit of Measure: Participants
3
  23.1%
5
  38.5%
8
  30.8%
6.Secondary Outcome
Title Post Void Residual (PVR)
Hide Description Distribution of patients with volume in ml of post-void residual urine obtained via catheter greater than 200 ml at 2-week follow-up appointment.
Time Frame 2 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
One patient did not complete 2-week follow-up post-void residual exam.
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

25 participants
Overall Number of Participants Analyzed 13 12 25
Measure Type: Count of Participants
Unit of Measure: Participants
2
  15.4%
3
  25.0%
5
  20.0%
7.Secondary Outcome
Title Number of Participants With Evidence of Infection or Positive Urine Culture
Hide Description Urinalysis results showing evidence of infection or positive urine culture at 2-week follow-up appointment.
Time Frame 2 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
One patient did not complete 2-week follow-up appointment.
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

25 participants
Overall Number of Participants Analyzed 13 12 25
Measure Type: Count of Participants
Unit of Measure: Participants
2
  15.4%
4
  33.3%
6
  24.0%
8.Secondary Outcome
Title Participant Satisfaction With Pain Control
Hide Description Measured using one question Likert scale. This will be a 4-level scale ranging from 'not at all satisfied,' 'slightly satisfied,' 'mostly satisfied,' and 'very much satisfied.'
Time Frame Postoperative (within 10 minutes of the end of the BoNT procedure)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description:

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

26 participants
Overall Number of Participants Analyzed 13 13 26
Measure Type: Count of Participants
Unit of Measure: Participants
Not at all satisfied
0
   0.0%
1
   7.7%
1
   3.8%
Slightly satisfied
2
  15.4%
1
   7.7%
3
  11.5%
Mostly satisfied
2
  15.4%
5
  38.5%
7
  26.9%
Very much satisfied
9
  69.2%
6
  46.2%
15
  57.7%
Time Frame Two-weeks
Adverse Event Reporting Description Adverse event reporting is applicable to only participants that completed the two week follow-up visit post-operative. Thus, only 25 participants are included.
 
Arm/Group Title Active B&O Suppository of Belladonna Placebo Suppository Total
Hide Arm/Group Description

Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.

Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg

Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.

Onabotulinumtoxin A (BoNT)

Placebo: matching placebo to B&O suppository

25 participants completed the two-week follow-up visit
All-Cause Mortality
Active B&O Suppository of Belladonna Placebo Suppository Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)      0/12 (0.00%)      0/25 (0.00%)    
Hide Serious Adverse Events
Active B&O Suppository of Belladonna Placebo Suppository Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      0/12 (0.00%)      0/25 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Active B&O Suppository of Belladonna Placebo Suppository Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/13 (15.38%)      4/12 (33.33%)      6/25 (24.00%)    
Infections and infestations       
Urinary Tract Infection Two Weeks Post-operative  [1]  2/13 (15.38%)  13 4/12 (33.33%)  12 6/25 (24.00%)  25
Indicates events were collected by systematic assessment
[1]
At the two week follow-up appointment, when indicated, specimens were sent for confirmatory culture if urinalysis indicated infection and empiric antibiotic treatment was initiated.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jennifer Duong, MPH, Research Associate
Organization: University of Kansas School of Medicine-Wichita
Phone: 316-962-3126
EMail: jduong@kumc.edu
Layout table for additonal information
Responsible Party: Edgar LeClaire, MD, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT02600715    
Other Study ID Numbers: STUDY00003056
15-051 ( Other Identifier: Wichita Medical Research and Education Foundation IRB )
First Submitted: October 29, 2015
First Posted: November 9, 2015
Results First Submitted: June 26, 2018
Results First Posted: September 20, 2018
Last Update Posted: September 20, 2018