The PINNACLE study is a prospective, multicenter, randomized study evaluating the safety and effectiveness of the Optilume BPH Catheter System. The study was conducted at 18 investigation centers in North America (NCT04131907). One-hundred forty-eight adult males with symptomatic BPH were enrolled and randomized in a 2:1 fashion to Optilume BPH or Sham (100 Optilume BPH; 48 Sham). The research was conducted following the guidelines of the Declaration of Helsinki. Approval for the protocol was obtained from the institutional review boards at each participating site, and written informed consent was acquired from all participants before their involvement.

Eligibility criteria included individuals aged between 50 and 80 years with an International Prostate Symptom Score (IPSS) ≥ 13, a peak urinary flow rate (Qmax) between 5 and 12 mL/s, a prostate volume between 20 and 80 g, and a prostatic urethral length between 32 and 55 mm as determined by transrectal ultrasound (TRUS). Patients were excluded if they had undergone prior minimally invasive or surgical interventions on the prostate, had a prostate-specific antigen >10 ng/mL without a negative biopsy, had a diagnosis or suspicion of cancer in the prostate or bladder, or had a urinary tract diagnosis with potential impact on urinary function such as stricture. A period of washout of BPH medications (i.e., 6 months for 5-alpha reductase inhibitors (5-ARI) and 2 weeks for phosphodiesterase-5 (PDE5) inhibitors and alpha blockers was required prior to completion of baseline assessments. Prior to treatment, participants were counseled to abstain from sex or use barrier contraception for 30 days post treatment to avoid exposure of a sexual partner to paclitaxel.

Briefly, the Optilume BPH catheter system consists of two dilation balloon catheters: one uncoated pre-dilation catheter and one drug-coated balloon catheter. During the Optilume BPH procedure, cystoscopy with a 20 F rigid scope is performed, followed by the insertion of the uncoated pre-dilation catheter under direct visualization. The correct placement of the catheter is aided by a blue mark visible on the catheter shaft, indicating its position at the distal end of the external sphincter. Subsequently, the pre-dilation catheter is dilated for approximately 1 min, creating the anterior commissurotomy. The drug-coated balloon is then inserted and placed similarly to the pre-dilation catheter, and it is inflated for at least 5 min. A Foley catheter is left in place for a minimum of 2 days after the completion of the procedure.

Participants were blinded to the treatment they received. Participants experiencing ongoing or recurrent LUTS secondary to BPH were counseled on treatment options by blinded site personnel. Participants who desired additional therapy had their blind broken to further discuss treatment options, including restarting medications, alternative MIST treatment, or TURP.

After treatment, follow-up was required at 14 days, 30 days, 3 months, 6 months, and at 1 year after treatment in both arms. Participants randomized to the Sham group are followed to 1 year and discontinued from the study. Those randomized to the Optilume BPH treatment group are followed annually through 5 years. Assessments at annual follow-up include IPSS, BPH Impact Index (BPH-II), International Index of Erectile Function (IIEF), EQ-5D, Male Sexual Health Questionnaire (MSHQ) to assess ejaculatory function (EjD), and uroflowmetry to assess Qmax and post-void residual urine (PVR). A voided volume ≥150 mL was required to be considered a valid uroflowmetry assessment.

Participants in either group had the option to choose standard of care or other alternative treatments for persistent or recurring LUTS related to BPH at any point. Those in the Optilume BPH Catheter System group who decided to pursue alternative treatment were withdrawn from the study and monitored solely for general health outcomes for up to 5 years after treatment.

Randomization was conducted using an electronic system employing permuted blocks stratified by center and baseline IPSS severity (≤19 vs. >19). Descriptive statistics were used to present study variables during follow-up, with continuous data presented as mean (SD) and categorical data as proportion (percent). Participants initially treated with Optilume BPH who require alternative therapy are considered treatment failures and are discontinued from the study. To accurately reflect the rate of symptomatic responders (≥30% improvement in IPSS and no medical or surgical retreatment), timepoints after study exit due to treatment failure are imputed as failures and included in the denominator. Confidence intervals for symptomatic responder rates are estimated using the Clopper-Pearson (exact) approach. P-values presented are nominal and not adjusted for multiple comparisons.