Over the last years, the disease management of lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) have been consistently improved. In particular, tadalafil 5 mg has been licensed for the treatment of male LUTS/BPE. Recently, the PROCOMB trial demonstrated the efficacy of the combination treatment with Serenoa Repens, Lycopene (Ly), and Selenium (Se) and tamsulosin than single therapies (SeR-Ly-Se or Tamsulosin) in improving IPSS and increasing Qmax in patients with LUTS at 12 months. Although either Tadalafil 5 mg and Se-Ly-Se have been test versus tamsulosin, there are no data about their comparison . For this reason, the aim of this phase IV, randomized, multicenter, non inferiority clinical study was to evaluate the efficacy and tolerability of the therapy Serenoa repens, selenium and lycopene (Profluss®) versus a Tadalafil® 5 mg for 6 months for the treatment of LUTS/BPE.
From April 2015 to September 2016, 439 men aged between 50 and 75, with digital rectal examination negative for prostate cancer, prostate specific antigen (PSA) < 4ng/ml, IPSS ≥12, PVR <100 ml, peak flow between 4 and 15 ml/s were screened (ISRCTN73316039) from 21 Italian urological centres. After screening and eventually pharmacological wash-out, the participants were off-site central randomized with a 2:1 ratio into SeR-Se-Ly for 6 months (Group A; n= 300) or Tadalafil 5 mg for 6 months (Group B; n= 139). It was a non inferiority randomized clinical study. Two sided noninferiority test using one-sided of a levle with 95% power assuming an equivalence margin of 0.5 for the IPSS and 0.8 for the peak flow, requiring 300 patients. The sample size was set at 330 (assuming a 10% drop- outs) using one-sided of a level of 0.05 with 95% power. The co-primary endpoints of the study were the changes of IPSS and peak flow after 6 months. The secondary endpoint was the reduction of post-void residual (PVR). One tablet of Profluss1 consisted of 320 mg of supercritical CO2 lipidic extract SeR containing 85% of fatty acids sterols, selenium (50mcg) and lycopene (5mg) and distributed by Konpharma Srl (Rome, Italy). The Treatment-related adverse events (TEAEs) were collected.
A total of 303 patients concluded the study protocol, 199 in the group A and 104 in the group B. All patients were balanced at baseline and any statistical difference was found when considering age, IPSS, peak flow, prostate volume, PVR and IIEF-5. After 6 months of therapy we observed a decrease in IPSS of -3 (95%CI -4;-3) and of -3 (95%CI -3;-2) in the group A and B respectively (non inferiority test p=0.04), an increase in peak flow of 2 (95%CI 2;4) and of 2 (95% 1;3) in the group A and B respectively (non inferiority test p<0.01) and a decrease in PVR of -12 (95%CI -32;-2) and of -10 (95% -25; -5) in the group A and B respectively (non inferiority test p=0.04). We observed a total of 25 (0.08%) of TEAEs, 5 in the group A (0.02%) and 20 in the group B (0.19%)(p<0.05).
In this phase IV randomized, non-inferiority clinical trial, we demonstrated that treatment with SeR-Se-Ly was not inferior to Tadalafil 5 mg after 6 months in patients affected by LUTS/BPE in terms of clinical efficacy. Furthermore SeR-Se-Ly showed less TEAEs compared to Tadalafil 5 mg.
