The efficacy of combination therapy with Ningmitai capsule and sildenafil in men with chronic prostatitis/chronic pelvic pain syndrome and erectile dysfunction: a prospective, multicenter, randomized controlled trial.

Abstract

Background: A high proportion of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) present with comorbid erectile dysfunction (ED), but evidence-based therapeutic interventions specifically targeting this patient population remain understudied in clinical trials.

Aim: To assess the efficacy of Ningmitai capsule (NMT), an oral traditional Chinese herbal formulation, combined with sildenafil versus monotherapy in alleviating symptoms among a cohort of participants with CP/CPPS and ED.

Methods: A multi-center, randomized clinical trial was conducted from March 2019 to December 2022 at six tertiary hospitals in China. A total of 214 participants diagnosed with CP/CPPS and ED were randomized 1:2:2 to receive orally sildenafil (25 mg, q.n.), NMT (0.38 g × 4 capsules, t.i.d.), or a combination of both for 4 weeks. Validated Chinese version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF-5) and the Erection Hardness Score (EHS) questionnaires were administered at baseline, week 2, and week 4.

Outcomes: The primary endpoint was the reduction in NIH-CPSI pain domain scores from baseline to week 4.

Results: All treatment groups exhibited statistically significant decreases in NIH-CPSI total, pain, urinary and quality of life (QoL) domain scores within 2 weeks, with improvements sustained until the end of the treatment. The combination group demonstrated superior pain score reductions versus sildenafil monotherapy at both timepoints (week 2: mean difference [MD] -2.82 ± 3.27 vs. -1.26 ± 3.45, P = 0.043; week 4, MD -3.57 ± 3.50 vs. -1.07 ± 2.94, P = 0.009). Notably, combination therapy achieved greater IIEF-5 score enhancements compared to NMT alone (P < 0.05) and higher responder rates than either sildenafil or NMT monotherapy (P < 0.05). No significant differences were found among the three arms concerning EHS. No adverse events were reported.

Clinical implications: NMT-sildenafil combination therapy may serve as a viable alternative to α-blocker-based regimens for CP/CPPS-ED patients, potentially circumventing the orthostatic hypotension risk associated with the concurrent use of phosphodiesterase 5 inhibitors (PDE5i) and α-blockers.

Strengths and limitations: Strengths include a prospective randomized design, which is well controlled. Limitations encompass the absence of placebo control and long-term follow-up.

Conclusion: NMT-sildenafil combination therapy demonstrates significantly greater benefits of ameliorating pain symptoms and improving erectile function in men with CP/CPPS and ED compared to either monotherapy, with favorable tolerability profiles.

Registration: The study protocol was reviewed and approved by the institutional ethics committee and was registered at ClinicalTrials.gov (NCT06064448).