Montorsi 2014.
| Methods |
Study design: randomised double‐blind placebo‐controlled trial Setting/country: 50 centres from 9 European countries and Canada Dates when study was conducted: November 2009 to August 2011 |
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| Participants |
Inclusion criteria: men aged < 68 years at the time of nsRP with normal preoperative EF who underwent nsRP for organ‐confined, non‐metastatic prostate cancer (Gleason score ≤ 7, PSA < 10 ng/mL). Postsurgical inclusion criteria included the development of ED, as measured by a participant‐reported Residual Erection Function score of ≤ 3 ("penis is hard enough for penetration but not completely hard"). Exclusion criteria: men with no history of ED, who had received previous or current treatment with tadalafil or any other PDE5I; had undergone, or planned to undergo, radiation or hormonal therapy for prostate cancer; history of prostatic surgery or prostatic physical treatments; history of diabetes mellitus; history of galactose intolerance, lapp lactase deficiency or glucose‐galactose malabsorption; clinically significant renal insufficiency as determined by the investigator Total number of participants randomly assigned: 423 Group A
Group B
Group C
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| Interventions |
Group A: tadalafil 5 mg once daily Group B: on‐demand tadalafil 20 mg Group C: placebo Surgery or cointervention: bilateral nerve‐sparing surgery during screening period Interval between surgery and intervention: NR Intervention duration: 9 months Washout period before outcome assessment: 6 weeks (washout) followed by 3 months' open label Total follow‐up period: 13.5 months (after 3 months' open label) |
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| Outcomes |
Primary outcomes
How measured: proportion of men achieving an IIEF‐EF score ≥ 22 Time points measured: at end of DFW Time points reported: at end of DFW (primary outcome) Secondary outcomes
How measured: Montorsi 2014: IIEF and SEP Questionnaire: measurements were taken before administration of any sedatives or anaesthetics. Moncada 2015: defined as the time from baseline to reach an IIEF‐EF ≥ 22 during DBT IIEF‐EF scores were categorised into the following ED severity categories: severe (0–10), moderate (11–16), mild (17–25) and normal (26–30). ED severity was assessed at baseline, end of DBT, and end of DFW. Improvement was defined as an IIEF‐EF score of ≥ 1 category higher than baseline (or maintaining normal EF) at the end of DBT. Maintenance of treatment response, assessed for participants who improved ≥ 1 category after DBT, was defined as either maintaining this improved category until the end of DFW or declining after DBT but still maintaining a higher category at the end of DFW than at baseline. Time points measured: Montorsi 2014 (at 9, 10.5 and 13 months, before RP and 9 months (after DBT))/Moncada 2015 (time to event: at baseline, end of DBT and end of DFW; at the end of DBT; at baseline, DBT and DFW) Time points reported: Montorsi 2014 (at 9, 10.5 and 13 months, before RP and 9 months (after DBT))/Moncada 2015 (time to event: at baseline, end of DBT and end of DFW; at the end of DBT; at baseline, DBT and DFW) Safety outcomes How measured: adverse events Time points measured: after DBT Time points reported: after DBT Subgroup: none |
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| Funding sources | Eli Lilly | |
| Declarations of interest | I Moncada has been a consultant for, and received speaker honoraria and travel expenses from, Eli Lilly. C Henneges, C Turbi and H Buettner are employees of Eli Lilly and Company and own Eli Lilly stock. FR de Bethencourt, E Lledó‐García, JI Martinez‐Salamanca and J Romero‐Otero have no conflicts of interest to disclose. | |
| Notes |
Protocol: NCT01026818 Language of publication: English |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not described |
| Allocation concealment (selection bias) | Low risk | Quote: "interactive voice response system and stratified by age group and country." |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Matching placebo tablets identical to the 5‐mg and 20‐mg tadalafil tablets were used to ensure that the blinded regimen was identical." Judgement: "Double‐blind (Participants and investigator)" in protocol and "placebo controlled" in article. |
| Blinding of outcome assessment (detection bias) Subjective outcomes | Low risk | Quote: "Matching placebo tablets identical to the 5‐mg and 20‐mg tadalafil tablets were used to ensure that the blinded regimen was identical." Judgement: "Double‐blind (Participants and investigator)" in protocol and "placebo controlled" in article. |
| Blinding of outcome assessment (detection bias) Objective outcomes | Low risk | Objective outcome not likely affected by lack of blinding. |
| Incomplete outcome data (attrition bias) Self‐reported potency | Low risk | All participants were included in the analysis except 1 participant in tadalafil on‐demand group. |
| Incomplete outcome data (attrition bias) EF/IIEF | Low risk | All participants were included in the analysis except 1 participant in tadalafil on‐demand group. |
| Incomplete outcome data (attrition bias) Serious adverse event | Unclear risk | All participants were included in the analysis. |
| Incomplete outcome data (attrition bias) Sexual quality of life | Low risk | All participants were included in the analysis except 1 participant in tadalafil on‐demand group. |
| Incomplete outcome data (attrition bias) Treatment discontinuation | Low risk | All participants were included in the analysis. |
| Incomplete outcome data (attrition bias) Acceptability of the intervention | Unclear risk | No information given |
| Selective reporting (reporting bias) | Unclear risk | While protocol was published, a few predefined outcomes in protocol were not reported in article. |
| Other bias | Low risk | Not detected |