The effect of combination treatment with low-intensity shockwave therapy and daily tadalafil on severe erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial.

BACKGROUND: Patients with severe erectile dysfunction (ED) remain the most challenging group in terms of available noninvasive treatment modalities. AIM: The study sought to assess the role of combination therapy with low-intensity shockwave therapy (LiST) and daily tadalafil 5 mg in a highly select group of patients with severe vasculogenic ED through a double-blind, randomized trial. METHODS: Forty-eight sexually active men were randomly assigned to 12 sessions of LiST 3 times weekly and tadalafil 5 mg once daily (n = 34) or sham therapy and tadalafil (n = 17) for 4 weeks. Patients were assessed at 1 and 3 months after completion of treatment. OUTCOMES: Improvement of erectile function was evaluated through the International Index of Erectile Function-Erectile Function domain (IIEF-EF) or 6-item IIEF and the Sexual Encounter Profile (SEP) diary. The primary outcome was the difference between the groups in the IIEF-EF at 3 months after completion of treatment. Secondary outcomes comprised (1) the difference between the groups in the IIEF-EF at 1 month after completion of treatment, (2) the difference between the groups in the "yes" responses to question 3 of the SEP diary at 1 and 3 months, and (3) the treatment-related adverse events. The number of patients attaining a minimal clinically important difference in the IIEF-EF (improvement of at least 7 points) was also assessed. RESULTS: After treatment, the absolute scores in the IIEF-EF were higher in patients receiving LiST and tadalafil vs sham therapy and tadalafil both at the 1-month (12.1 ± 2.4 vs 10.2 ± 1.7; P = .002) and at the 3-month (12.9 ± 2.1 vs 10.8 ± 1.8; P < .001) evaluation. Between the 2 groups, the proportion of "yes" responses to question 3 of the SEP diary was not statistically significant, whereas the number of patients attaining a minimal clinically important difference in the IIEF-EF was statistically significant only at the 3-month evaluation. No adverse events occurred. CLINICAL IMPLICATIONS: Application of LiST in patients with severe vasculogenic ED receiving daily dose tadalafil may further improve erectile function compared with tadalafil as a stand-alone treatment on the short term. STRENGTHS AND LIMITATIONS: Although we provided the first study in the field, severe vasculogenic ED was defined based on medical history and clinical examination and not based on penile ultrasound measures. CONCLUSION: The combination of 12 sessions LiST 3 times weekly and daily tadalafil for 4 weeks led to a 2-point difference in the IIEF-EF compared with sham therapy and daily tadalafil among patients with severe vasculogenic ED after 1 and 3 months from completion of treatment.

The Effect of Low-Intensity Shock Wave Therapy on Moderate Erectile Dysfunction: A Double-Blind, Randomized, Sham-Controlled Clinical Trial.

PURPOSE: We conducted the first double-blind, randomized, sham-controlled trial evaluating the efficacy and safety of low-intensity shock wave therapy (LiST) exclusively in patients with moderate erectile dysfunction. MATERIALS AND METHODS: Seventy patients were randomized to 12 sessions of LiST (35) or sham therapy (35) twice weekly. Patients were evaluated at 1 and 3 months after completion of treatment. The proportion of participants attaining minimal clinically important difference (MCID) in the International Index of Erectile Function-Erectile Function (IIEF-EF) and the effect of LiST on erectile function, as well as on safety, were the study outcomes. RESULTS: At 3 months, MCID was attained by 27 (79%) patients in the LiST group compared to 0 patients in the sham group. The risk difference between the 2 groups was 79% (95% confidence interval [CI]: 66-93, p <0.001) and the baseline-adjusted mean between-group-difference in the IIEF-EF was 4.4 points (95% CI: 3.4-5.4, p <0.001). At 1 month, MCID was attained by 20 (59%) patients in the LiST group compared to 1 (2.9%) patient in the sham group. The risk difference between the 2 groups was 56% (95% CI: 38-73, p <0.001) and the baseline-adjusted mean between-group-difference in the IIEF-EF was 3.9 points (95% CI: 2.7-5.2, p <0.001). CONCLUSIONS: Twelve sessions of LiST twice weekly for 6 weeks with a treatment protocol of 5,000 impulses, 0.096 mJ/mm2 energy flux density and 5 Hz frequency are highly effective in patients with moderate erectile dysfunction. Still, further long-term randomized studies are warranted to corroborate our findings.

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Combination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach. AIM: To conduct the first double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of combination therapy with low-intensity shockwave therapy (LiST) and tadalafil vs LiST and placebo in patients with mild or mild-to-moderate vasculogenic ED. METHODS: Fifty sexually active patients fulfilling the eligibility criteria were randomly assigned to 6 sessions of LiST twice weekly for 3 weeks and tadalafil (n = 25) or placebo (n = 25) once daily for 4 weeks. Patients were evaluated at 1, 3, and 6 months after completion of the treatment protocol. OUTCOMES: The primary outcome was the mean change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain between the 2 groups at 3 months after treatment. Erectile function was also assessed at 1 and 6 months. The number of patients attaining a minimal clinically important difference (MCID) in the IIEF-EF, as well as the safety of combination therapy were evaluated. RESULTS: Adjusting for the baseline values, IIEF-EF improved by 0.8 points more (95% confidence interval [CI] = -0.2 to 1.9, P = .12) at 1 month, 1 point more (95% CI = 0.1-1.9, P = .02) at 3 months and 1.7 points more (95% CI = 0.8-2.7, P < .001) at 6 months in patients treated with combination therapy compared to monotherapy. The number of patients attaining a MCID in the IIEF-EF between the 2 groups improved significantly only at the 3-month evaluation. No adverse events were reported during the whole study period. CLINICAL IMPLICATIONS: Combination of LiST twice weekly for 3 weeks and tadalafil 5 mg once daily for 4 weeks may further ameliorate mild or mild-to-moderate vasculogenic ED compared to LiST monotherapy. STRENGTHS & LIMITATIONS: We conducted the first randomized trial exploring the role of LiST and tadalafil in the management of ED. Conversely, our study lacks external validity due to its single-center design. CONCLUSION: The addition of daily low-dose tadalafil during application of LiST may further improve erectile function compared to application of LiST as a standalone treatment in patients with mild or mild-to-moderate vasculogenic ED. Still, further high-quality studies are warranted to corroborate our findings. Mykoniatis I, Pyrgidis N, Zilotis F, et al. The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2022;19:106-115.