Prostatic Hypertrophy, Benign
Conditions
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.
Interventions
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.
DRUGPlacebo
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.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
Countries
Germany
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 details
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
Participants by arm
| Arm | Count |
|---|---|
| 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 GreenlightTM laser ablation of prostate commences. | 25 |
| 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 GreenlightTM laser ablation of prostate commences | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Vardenafil (Levitra, BAY38-9456) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 7.5 | 65.9 years STANDARD_DEVIATION 7.9 | 65.9 years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 25 | 2 / 25 |
| serious Total, serious adverse events | 1 / 25 | 2 / 25 |
Outcome results
Primary
Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | baseline mean | 8.3 milliliter per second (mL/s) | Standard Deviation 4.08 |
| Vardenafil (Levitra, BAY38-9456) | Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | Day +90 or LOCF mean | 23.1 milliliter per second (mL/s) | Standard Deviation 10.6 |
| Placebo | Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | Day +90 or LOCF mean | 25.7 milliliter per second (mL/s) | Standard Deviation 7.9 |
| Placebo | Baseline-adjusted Least Squared (LS) Means of Peak Urinary Flow (Qmax) at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | baseline mean | 9.4 milliliter per second (mL/s) | Standard Deviation 5.69 |
Comparison: null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90p-value: 0.524895% CI: [-4.18, 8.05]ANCOVA
Secondary
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 (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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | 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 mean | 19.1 scores on a scale | Standard Deviation 5.92 |
| Vardenafil (Levitra, BAY38-9456) | 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) | Day +90 or LOCF mean | 6.9 scores on a scale | Standard Deviation 4.25 |
| Placebo | 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 mean | 19.7 scores on a scale | Standard Deviation 5.83 |
| Placebo | 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) | Day +90 or LOCF mean | 6.7 scores on a scale | Standard Deviation 6.03 |
Comparison: null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90p-value: 0.8795% CI: [-3.58, 3.04]ANCOVA
Secondary
Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | baseline mean | 139.3 milliliter (mL) | Standard Deviation 116.43 |
| Vardenafil (Levitra, BAY38-9456) | Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | Day +90 or LOCF mean | 18.7 milliliter (mL) | Standard Deviation 23.55 |
| Placebo | Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | baseline mean | 117.4 milliliter (mL) | Standard Deviation 81.42 |
| Placebo | Baseline-adjusted Least Squared (LS) Means of Post-void Residual (PVR) Volume at 3 Months After Surgery or Last Observation Carried Forward (LOCF) | Day +90 or LOCF mean | 22.5 milliliter (mL) | Standard Deviation 18.34 |
Comparison: null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90p-value: 0.416295% CI: [-8.21, 19.35]ANCOVA
Secondary
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 (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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | 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 mean | 8.4 urinary incontinence episodes | Standard Deviation 25.71 |
| Vardenafil (Levitra, BAY38-9456) | 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) | Day +90 or LOCF mean | 7.1 urinary incontinence episodes | Standard Deviation 13.42 |
| Placebo | 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 mean | 0.0 urinary incontinence episodes | Standard Deviation 0 |
| Placebo | 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) | Day +90 or LOCF mean | 0.4 urinary incontinence episodes | Standard Deviation 1.42 |
Comparison: null hypothesis: mean of Vardenafil group equals mean of Placebo group at day +90p-value: 0.058895% CI: [-13.25, 0.26]ANCOVA
Secondary
Duration of Surgery
Duration of prostate laser ablation, i.e. Greenlight(TM) laser surgery.
Time frame: on the day of surgery, without any further allowable time window
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Duration of Surgery | 75.1 minutes | Standard Deviation 36.5 |
| Placebo | Duration of Surgery | 72.5 minutes | Standard Deviation 25.8 |
Comparison: null hypothesis: mean of Vardenafil group equals mean of Placebo groupp-value: 0.787895% CI: [-22.03, 16.82]ANCOVA