Trial Outcomes & Findings for Botulinum Toxin Injection for the Management of BPH (NCT NCT00451191)

Results Overview

The primary outcome was treatment success at 3 months post-treatment, defined as (1) improvement in the AUASI by at least 30% and/or (2) Qmax improvement of more than 30%, each determined from baseline to 3 months after injection. In addition, two safety criteria also had to be met; a dose failed if (1) any reported event was determined to be related to the onabotulinum toxin A injection and was considered life threatening, disabling, or fatal or (2) \>=40% of the participants reported a moderate or severe side effect related to the botulinum toxin injection.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

134 participants

Primary outcome timeframe

12 weeks

Results posted on

2020-04-21

Participant Flow

Patients were recruited at the 7 clinical centers (Baylor College of Medicine, Houston TX; Cornell University, New York NY; Mayo Clinic, Rochester MN; Medical College of Wisconsin, Milwaukee WI; Northwestern University, Chicago IL; University of Colorado Denver, Aurora CO; University of Texas Southwestern Medical Center, Dallas TX).

Screening for eligibility: male, 50+ years old, signed informed consent, no prior surgical treatment for BPH and no prior use of botulinum toxin, appropriate washout period for medical therapy, American Urological Association Symptom Index (AUASI) \>=8, voided volume \>=125 ml, maximum urinary flow rate \<15 ml/sec.

Participant milestones

Participant milestones
Measure	100 Units Botulinum Toxin Type A botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	300 Units Botulinum Toxin Type A botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.
Overall Study STARTED	68	66
Overall Study COMPLETED	53	55
Overall Study NOT COMPLETED	15	11

Reasons for withdrawal

Reasons for withdrawal
Measure	100 Units Botulinum Toxin Type A botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	300 Units Botulinum Toxin Type A botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.
Overall Study withdrawal or received alternate tx	15	11

Baseline Characteristics

Botulinum Toxin Injection for the Management of BPH

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	100 Units Botulinum Toxin Type A n=68 Participants botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	300 Units Botulinum Toxin Type A n=66 Participants botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	Total n=134 Participants Total of all reporting groups
Age, Customized <50 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized >=50 years	68 participants n=5 Participants	66 participants n=7 Participants	134 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	66 Participants n=7 Participants	134 Participants n=5 Participants
Region of Enrollment United States	68 participants n=5 Participants	66 participants n=7 Participants	134 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: By the last 12-month follow-up visit, 15 men (22%) in the 100 U dose arm and 11 (17%) in the 300 U dose arm had withdrawn due to dissatisfaction with treatment results or continued to attend study follow-up but received additional alternate treatment prior to 12 months.

The primary outcome was treatment success at 3 months post-treatment, defined as (1) improvement in the AUASI by at least 30% and/or (2) Qmax improvement of more than 30%, each determined from baseline to 3 months after injection. In addition, two safety criteria also had to be met; a dose failed if (1) any reported event was determined to be related to the onabotulinum toxin A injection and was considered life threatening, disabling, or fatal or (2) \>=40% of the participants reported a moderate or severe side effect related to the botulinum toxin injection.

Outcome measures

Outcome measures
Measure	100 Units Botulinum Toxin Type A n=53 Participants botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	300 Units Botulinum Toxin Type A n=55 Participants botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.
Improvement in the AUA Symptom Score Index by 30% From Baseline Within the First 12 Weeks After Injection.	46 participants	50 participants

Adverse Events

100 Units Botulinum Toxin Type A

Serious events: 7 serious events

Other events: 46 other events

Deaths: 0 deaths

300 Units Botulinum Toxin Type A

Serious events: 5 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	100 Units Botulinum Toxin Type A n=68 participants at risk botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	300 Units Botulinum Toxin Type A n=66 participants at risk botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.
General disorders Grade 2 - 4 Serious Adverse Event	8.8% 6/68 • Number of events 6 • 12 months Adverse and serious adverse events were collected at scheduled study visits or by participant contact between visits. A standard form was completed.	7.6% 5/66 • Number of events 6 • 12 months Adverse and serious adverse events were collected at scheduled study visits or by participant contact between visits. A standard form was completed.
General disorders Grade 5 Serious Adverse Event (Death)	1.5% 1/68 • Number of events 1 • 12 months Adverse and serious adverse events were collected at scheduled study visits or by participant contact between visits. A standard form was completed.	0.00% 0/66 • 12 months Adverse and serious adverse events were collected at scheduled study visits or by participant contact between visits. A standard form was completed.

Other adverse events

Other adverse events
Measure	100 Units Botulinum Toxin Type A n=68 participants at risk botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.	300 Units Botulinum Toxin Type A n=66 participants at risk botulinum toxin type A (BoNT/A) : 100 unit and 300 unit dosages: Dilute each 100 U vial with 1.3 ml of normal saline. Each reconstituted vial is then drawn up into a single syringe with a total of 4 ml = 300 U. The instrument used to inject the botulinum toxin is an ultrasound device with a transrectal ultrasound probe specially designed for prostate biopsies which has a special canal to introduce and direct a needle in to the selected prostatic area.
General disorders Grade 1-3 Adverse Event	67.6% 46/68 • Number of events 116 • 12 months Adverse and serious adverse events were collected at scheduled study visits or by participant contact between visits. A standard form was completed.	62.1% 41/66 • Number of events 109 • 12 months Adverse and serious adverse events were collected at scheduled study visits or by participant contact between visits. A standard form was completed.

Additional Information

Kathryn Hirst, PhD, Research Professor, PI of coordinating center

George Washington University Biostatistics Center

Phone: 301-881-9260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place