Vardenafil in Greenlight(TM) Laser Surgery of Benign Prostate Hypertrophy

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00461123
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

The greenlight laser has an absorption maximum which is exactly the same as for hemoglobin. In the presence of hemoglobin, its application causes vaporization of the tissue and this effect depends on the concentration of hemoglobin in the respective tissue. Therefore, increase of blood-flow in the tissue (here: prostate gland) should exert better efficacy of the laser application and consequently shortening of the required duration of laser application.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hypertrophy, Benign	Drug: Vardenafil (Levitra, BAY38-9456); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Parallel Group Prospective Pilot Study to Assess the Effect of Vardenafil on Clinical Outcome and on Procedure Duration After Green Light Laser-ablation of the Prostate Gland for Therapy of Benign Prostate Hypertrophy (BPH)
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vardenafil (Levitra, BAY38-9456) One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before Greenlight(TM) laser ablation of prostate commenced.	Drug: Vardenafil (Levitra, BAY38-9456); One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before Greenlight(TM) laser ablation of prostate commenced.
Placebo Comparator: Placebo One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before Greenlight(TM) laser ablation of prostate commenced.	Drug: Placebo; One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before Greenlight(TM) laser ablation of prostate commenced.

Outcome Measures

Primary Outcome Measures

1. Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF) [baseline and up to 3 months after surgery]

   Baseline (pre-surgery Day -1) adjusted least squares (LS)-means at 3 months after surgery (Day +90, last observation carried forward (LOCF)) in peak urinary flow.

Secondary Outcome Measures

1. Baseline-adjusted Least Squared (LS) Means of International Prostate Symptom Score (IPSS) Total Score at 3 Months After Surgery or Last Observation Carried Forward (LOCF) [baseline and up to 3 months after surgery]

   Baseline (pre-surgery Day -1) adjusted LS-means at 3 months after surgery (Day +90, LOCF) in IPSS total score. IPSS is a questionnaire on benign prostate hyperplasia, including seven 6-point items on symptoms and one 7-point item on quality of life. Total score: sum of items 1 through 7; minimum: 0 (best); maximum: 41 (worst).

2. Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF) [baseline and up to 3 months after surgery]

   Baseline (pre-surgery Day -1) adjusted LS-means at 3 months after surgery (Day +90, last observation carried forward (LOCF)) in PVR volume. PVR is the amount of urine left in the bladder after a person has passed urine.

3. Baseline-adjusted Least Squared (LS) Means of the Number of Urinary Incontinence Episodes Per Week at 3 Months After Surgery or Last Observation Carried Forward (LOCF) [baseline and up to 3 months after surgery]

   Baseline (pre-surgery Day -1) adjusted LS-means at 3 months after surgery (Day +90, last observation carried forward (LOCF)) in the number of incontinence episodes. Urinary incontinence is an involuntary excretion (passing) of urine. Urinary incontinence episodes were collected in the patient diary.

4. Duration of Surgery [on the day of surgery, without any further allowable time window]

   Duration of prostate laser ablation, i.e. Greenlight(TM) laser surgery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men with benign prostate hypertrophy requiring surgical treatment

• Age up to 80 years

• Documented, dated, written Informed Consent

• Anesthesiologists agreement with swallowing 1 tablet one hour prior surgery

Exclusion Criteria:

• Any unstable medical, psychiatric, or substance abuse disorder

• History of previous prostatectomy

• Patients suspect of prostate cancer

• Hereditary degenerative retinal disorder

• History of previous Non-arteric Anterior Ischemic Optic Neuropathy (NAION) episode or unilateral vision impairment

• Any cardiovascular condition

• History of myocardial infarction, stroke or life-threatening arrhythmia within the prior 6 months

• Uncontrolled atrial fibrillation/flutter at screening

• Severe chronic or acute liver disease

• Chronic hematological disease which may lead to priapism

• Bleeding disorder

• Significant active peptic ulceration

• Resting hypotension

• History of positive test for Hepatitis B surface antigen or Hepatitis C

• Symptomatic postural hypotension within 6 months of Visit 1

• Patients who subjectively or in the opinion of the investigator did not tolerate the initial dose of study medication well

• Subjects who are taking nitrates or nitric oxide donors

• Subjects who are taking androgens or anti-androgens

• Subjects who are taking potent inhibitors of cytochrome P4503A4

• Subjects who have received any investigational drug within 30 days of Visit 1

• Using of alpha-blockers during two days prior to first dosing of study medication and after ablation of prostate

• Use of inhibitors of 5-alpha reductase after ablation of prostate

• Subjects with serum creatinine clearance <30.0 mL/min

• Elevation of Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) >3 times the upper limit of normal

• Subjects with known hypersensitivity to Vardenafil

• Subjects who are illiterate or unable to understand subject diaries

• Subjects who would be non-compliant with the study visit schedule

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Heidelberg	Baden-Württemberg	Germany	69112

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here and search for Bayer Product information by EMA

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00461123
• Other Study ID Numbers: 12496; 2006-004633-15
• First Posted: Apr 17, 2007
• Last Update Posted: Dec 19, 2014
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Prostatic Hyperplasia; Hypertrophy; Vardenafil Dihydrochloride

Study Results

Participant Flow

Recruitment Details	Enrollment started on 19 March 2007 and the last study visit occurred on 02 June 2008. The study was conducted at one center, a university clinic in Germany.
Pre-assignment Detail	Number of subjects enrolled, randomized and exposed to at least one dose (safety population): 50. Number of subjects who had undergone surgery, whose type of surgery (Greenlight(TM) laser-ablation) had not changed, energy consumption during surgery reported and who had taken the second dose on the day of surgery (intent-to-treat population): 44

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
Period Title: Overall Study
STARTED	25	25
COMPLETED	19	19
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo	Total
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.8 (7.5)	65.9 (7.9)	65.9 (7.6)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	25 100%	25 100%	50 100%

Outcome Measures

1. Primary Outcome

Title	Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF)
Description	Baseline (pre-surgery Day -1) adjusted least squares (LS)-means at 3 months after surgery (Day +90, last observation carried forward (LOCF)) in peak urinary flow.
Time Frame	baseline and up to 3 months after surgery

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population includes participants with baseline and post-baseline measurement of peak urinary flow; imputation technique: last post-baseline observation carried forward (LOCF). The ITT population is not identical to the number of subjects who "completed" the study, as displayed under Participants Flow.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
Measure Participants	19	18
baseline mean	8.3 (4.08)	9.4 (5.69)
Day +90 or LOCF mean	23.1 (10.60)	25.7 (7.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5248
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA), baseline as covariate, treatment as fixed factor
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.93
	Confidence Interval	() 95%; -4.18 to 8.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference of least squares (LS) means (Placebo minus Vardenafil)

2. Secondary Outcome

Title	Baseline-adjusted Least Squared (LS) Means of International Prostate Symptom Score (IPSS) Total Score at 3 Months After Surgery or Last Observation Carried Forward (LOCF)
Description	Baseline (pre-surgery Day -1) adjusted LS-means at 3 months after surgery (Day +90, LOCF) in IPSS total score. IPSS is a questionnaire on benign prostate hyperplasia, including seven 6-point items on symptoms and one 7-point item on quality of life. Total score: sum of items 1 through 7; minimum: 0 (best); maximum: 41 (worst).
Time Frame	baseline and up to 3 months after surgery

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population includes participants with baseline and post-baseline measurement of International Prostate Symptom Score (IPSS) total score; imputation technique: last post-baseline observation carried forward (LOCF). The ITT population is not identical to the number of subjects who "completed" the study.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
Measure Participants	20	19
baseline mean	19.1 (5.92)	19.7 (5.83)
Day +90 or LOCF mean	6.9 (4.25)	6.7 (6.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8700
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA), baseline as covariate, treatment as fixed factor
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.27
	Confidence Interval	() 95%; -3.58 to 3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference of LS means (Placebo minus Vardenafil)

3. Secondary Outcome

Title	Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF)
Description	Baseline (pre-surgery Day -1) adjusted LS-means at 3 months after surgery (Day +90, last observation carried forward (LOCF)) in PVR volume. PVR is the amount of urine left in the bladder after a person has passed urine.
Time Frame	baseline and up to 3 months after surgery

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population includes participants with baseline and post-baseline measurement of post-void residual (PVR) volume; imputation technique: last post-baseline observation carried forward (LOCF). The ITT population is not identical to the number of subjects who "completed" the study.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
Measure Participants	18	17
baseline mean	139.3 (116.43)	117.4 (81.42)
Day +90 or LOCF mean	18.7 (23.55)	22.5 (18.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4162
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA), baseline as covariate, treatment as fixed factor
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.57
	Confidence Interval	() 95%; -8.21 to 19.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference of LS means (Placebo minus Vardenafil)

4. Secondary Outcome

Title	Baseline-adjusted Least Squared (LS) Means of the Number of Urinary Incontinence Episodes Per Week at 3 Months After Surgery or Last Observation Carried Forward (LOCF)
Description	Baseline (pre-surgery Day -1) adjusted LS-means at 3 months after surgery (Day +90, last observation carried forward (LOCF)) in the number of incontinence episodes. Urinary incontinence is an involuntary excretion (passing) of urine. Urinary incontinence episodes were collected in the patient diary.
Time Frame	baseline and up to 3 months after surgery

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population includes participants with baseline and post-baseline documentation of number of incontinence episodes per week; imputation technique: last post-baseline observation carried forward (LOCF). The ITT population is not identical to the number of subjects who "completed" the study.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
Measure Participants	17	18
baseline mean	8.4 (25.71)	0.0 (0.00)
Day +90 or LOCF mean	7.1 (13.42)	0.4 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0588
	Comments
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA), baseline as covariate, treatment as fixed factor
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.50
	Confidence Interval	() 95%; -13.25 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference of LS means (Placebo minus Vardenafil)

5. Secondary Outcome

Title	Duration of Surgery
Description	Duration of prostate laser ablation, i.e. Greenlight(TM) laser surgery.
Time Frame	on the day of surgery, without any further allowable time window

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population includes participants with baseline and post-baseline measurement of duration of surgery; imputation technique: last post-baseline observation carried forward (LOCF). The ITT population is not identical to the number of subjects who "completed" the study.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.	One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
Measure Participants	23	21
Mean (Standard Deviation) [minutes]	75.1 (36.5)	72.5 (25.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	null hypothesis: mean of Vardenafil group equals mean of Placebo group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7878
	Comments
	Method	ANCOVA
	Comments	Analysis of variance (ANOVA), treatment as fixed factor
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.61
	Confidence Interval	() 95%; -22.03 to 16.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference of LS means (Placebo minus Vardenafil)

Adverse Events

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)		Placebo
Arm/Group Description	One tablet vardenafil 10 mg with a glass of water the evening before ablation of prostate; the second dose (vardenafil 20 mg) with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences.		One placebo tablet with a glass of water the evening before ablation of prostate; the second placebo dose with a glass of water approximately one hour before GreenlightTM laser ablation of prostate commences
All Cause Mortality
	Vardenafil (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vardenafil (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/25 (4%)		2/25 (8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/25 (0%)		1/25 (4%)
Prostate cancer	1/25 (4%)		0/25 (0%)
Renal and urinary disorders
Urinary retention	0/25 (0%)		1/25 (4%)
Other (Not Including Serious) Adverse Events
	Vardenafil (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/25 (8%)		2/25 (8%)
General disorders
Pyrexia	1/25 (4%)		0/25 (0%)
Infections and infestations
Urinary tract infection	0/25 (0%)		1/25 (4%)
Renal and urinary disorders
Urinary retention	0/25 (0%)		1/25 (4%)
Vascular disorders
Flushing	1/25 (4%)		0/25 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.