PINNACLE: Optilume BPH Paclitaxel-Coated Balloon Versus Sham
PINNACLE was a double-blind, sham-controlled randomized trial of Optilume BPH paclitaxel-coated balloon dilation versus a sham cystoscopic procedure in 148 men with lower urinary tract symptoms from BPH. The primary endpoint compared IPSS improvement at 12 months with Optilume BPH (11.5 points) against improvement at 3 months with sham (8.0 points) after adding a 25% super-superiority margin to the sham effect, and the trial did not meet it (difference 1.4 points, 95% CI −1.6 to 4.5; P = 0.178).[1][2]
- Design and population
- Multicenter, double-blind, sham-controlled randomized device trial. 148 men aged 50 to 80 years with symptomatic BPH, IPSS of 13 or more, Qmax 5 to 12 mL/s, prostate volume 20 to 80 g and prostatic urethral length 32 to 55 mm.
- Arms
- Optilume BPH paclitaxel-coated balloon dilation versus sham cystoscopic procedure with an uninflated predilation catheter
- Report and follow-up
- 2023 · 12 months (Optilume BPH arm) versus 3 months (sham arm, the primary comparison time point)
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| IPSS improvement from baseline, Optilume BPH at 12 months versus sham at 3 months, with a prespecified 25% super-superiority margin on the sham effect; difference = Optilume BPH minus sham with margin | 11.5 ± 7.8 points (n=100) vs 8.0 ± 8.3 points (n=48) | difference 1.4; CI -1.6–4.5; P 0.178 | Not met |
| IPSS improvement without the margin, Optilume BPH at 12 months minus sham at 3 months | 11.5 ± 7.8 points vs 8.0 ± 8.3 points | difference 3.4; CI 0.6–6.2; P 0.008 | Descriptive |
| Mean percent IPSS improvement from baseline to 12 months in the Optilume BPH arm against a prespecified performance goal of 30% | 49% (95% CI 42.7% to 55.4%) | P <0.001 | Not tested |
| Participants with at least 30% IPSS improvement, Optilume BPH at 12 months versus sham at 3 months | 76.6% (72/94) vs 52.1% (25/48) | P 0.003 | Not tested |
| Qmax change from baseline, Optilume BPH at 12 months versus sham at 3 months; difference = Optilume BPH minus sham | +9.7 ± 10.1 mL/s (n=87) vs +5.5 ± 7.4 mL/s (n=43) | difference 4.2; CI 0.8–7.6; P 0.009 | Not tested |
| Sham-arm IPSS improvement from baseline at 12 months | 4.8 points (21.5%) | — | Descriptive |
Harms: Serious adverse events judged related to the device: 5/98 (5.1%) vs 0/48; Hematuria (any, regardless of relatedness): 39/98 (40%); Urinary tract infection (any, regardless of relatedness): 14/98 (14%)
Design
Eighteen centers in the United States and Canada randomized 148 men between January 2020 and September 2021, 2:1 to Optilume BPH or sham, using permuted blocks stratified by center and baseline IPSS (19 or less versus more than 19). Men were 50 to 80 years old with an IPSS of at least 13, Qmax of 5 to 12 mL/s, prostate volume of 20 to 80 g and prostatic urethral length of 32 to 55 mm. Exclusions included prior minimally invasive or surgical prostate treatment, PSA above 10 ng/mL without a negative biopsy, suspected prostate or bladder cancer, active urinary tract infection, postvoid residual above 300 mL and confounding bladder or urethral diagnoses such as neurogenic bladder or stricture.[1] BPH medications were washed out first (2 weeks for alpha-blockers and phosphodiesterase type 5 inhibitors, 3 months for 5-alpha-reductase inhibitors targeting the type 2 isoenzyme, 6 months for nonspecific inhibitors).[1] The 2-year report adds exclusions for an artificial urinary sphincter, urethral or prostatic stents, an intravesical prostatic protrusion above 1 cm and prior pelvic radiation.[3]
Participants and evaluating personnel were blinded through 12 months, with assessments at 14 days, 30 days, 3, 6 and 12 months. Adverse events were adjudicated for relatedness and severity by a blinded clinical events committee. The primary endpoint compared IPSS improvement from baseline at 3 months in the sham arm with improvement at 12 months in the Optilume BPH arm; the FDA summary specifies that it incorporated a 25% super-superiority margin on the sham effect.[2] In the intention-to-treat analysis, a participant who received alternative BPH therapy before the scheduled time point was counted as having no improvement, and other missing IPSS values were imputed. Key secondary endpoints were the Qmax comparison, the proportion with a clinically meaningful IPSS improvement, and the Optilume BPH arm's percent IPSS improvement against a 30% performance goal.[1] Published P values for these are nominal and unadjusted.[1][2]
Results
In the intention-to-treat analysis, IPSS improved by 11.5 ± 7.8 points with Optilume BPH at 12 months and by 8.0 ± 8.3 points with sham at 3 months. The unadjusted difference was 3.4 points (95% CI 0.6 to 6.2; P = 0.008).[1] With the 25% margin the sham effect was 10.0 points, the difference fell to 1.4 points (95% CI −1.6 to 4.5; P = 0.178), and the primary endpoint was not met.[2] Five participants were imputed as having no improvement: four who received alternative BPH therapy and one who withdrew consent for perceived lack of effectiveness.[1][2]
Secondary hypotheses were not formally tested because the primary endpoint was not met. Descriptively, the Optilume BPH arm improved its IPSS by 49% (95% CI 42.7% to 55.4%) against the 30% goal.[2] At least 30% IPSS improvement occurred in 76.6% (72/94) of the Optilume BPH arm at 12 months and 52.1% (25/48) of the sham arm at 3 months (P = 0.003).[1][2] Qmax rose by 9.7 ± 10.1 mL/s (n = 87) with Optilume BPH at 12 months and 5.5 ± 7.4 mL/s (n = 43) with sham at 3 months (difference 4.2 mL/s, 95% CI 0.8 to 7.6; P = 0.009; voids under 150 mL excluded).[1][2]
Within the Optilume BPH arm, paired 12-month changes were IPSS −12.1 ± 7.5 points (n = 89; 23.0 to 10.9), IPSS quality of life −2.4 ± 1.9 points (n = 89), Qmax +10.3 ± 10.2 mL/s (n = 82; 8.7 to 19.0) and postvoid residual −25.2 ± 81.3 mL (n = 82).[1] The sham effect faded: sham IPSS improvement was 8.0 points (33.3%) at 3 months and 4.8 points (21.5%) at 12 months.[1] In a post hoc analysis in the FDA summary, the 12-month improvement of 11.5 points was compared with a pooled sham improvement at 3 months of 5.9 points (7.4 with the margin) from 8 published sham-controlled endoscopic BPH trials (n = 401).[2]
Erectile and ejaculatory scores did not differ between arms at 12 months. The IIEF erectile function domain changed by +0.9 ± 7.7 (n = 87) with Optilume BPH and +2.7 ± 7.1 (n = 26) with sham, and the MSHQ-EjD function score by +0.9 ± 3.5 (n = 87) and +0.2 ± 1.9 (n = 26).[1]
The 2-year report followed only the Optilume BPH arm; sham participants were followed for 1 year and could cross over. Of 83 men in the responder analysis (including treatment failures), 56 (67.5%; 95% CI 56.3% to 77.4%) had at least 30% IPSS improvement without medical or surgical retreatment. Paired IPSS fell by 12.1 ± 8.0 points (n = 74; 23.0 to 11.0) and Qmax rose by 10.3 ± 15.9 mL/s (n = 65; 8.7 to 19.0); the paired postvoid residual change of −18.1 mL (n = 65) was not significant (P = 0.151). Of the 100 men randomized to Optilume BPH, 3 (3%) had surgical reintervention (prostatic artery embolization, TURP or laser ablation) and 6 (6%) started medication.[3]
Surgery and treatment delivery
Treatment used a 20F rigid cystoscope. An uncoated predilation balloon was positioned with its blue marker at the distal edge of the external sphincter and inflated for about 1 minute to start an anterior commissurotomy. The 90F double-lobe drug-coated balloon, 30, 35, 40 or 45 mm long according to transrectal-ultrasound prostatic urethral length, was positioned the same way and inflated for at least 5 minutes. A Foley catheter was left for 2 days.[1]
The sham used rigid cystoscopy with a sheathed 21F predilation catheter that was not inflated, held for about 5 minutes, with a scripted staff dialogue, a drape blocking the participant's view and identical analgesia and catheterization protocols. Deep sedation or general anesthesia was used in 84.7% of the Optilume BPH arm and 87.5% of the sham arm (P = 0.9); moderate sedation and local prostate block were used at similar rates.[1] Procedure time (scope in to scope out) was 26 versus 8 minutes, and catheterization lasted 3.0 versus 2.5 days (P = 0.15). At Foley removal, all sham participants believed they had received Optilume BPH or were unsure, and 62.5% still did at 3 months.[1] Sham participants could break the blind and cross to Optilume BPH after the 3-month visit; 20 of the 48 did so before their 12-month visit.[1][2]
Adverse events
Five serious adverse events (5/98, 5.1%) were judged device-related: four postprocedural hematuria events needing cystoscopic management or extended observation, which resolved without sequelae, and one urethral false passage needing extended catheterization.[1][2] No sham participant had a related serious event. The FDA summary also lists one grade 3 bladder perforation adjudicated as procedure-related (6/98 treatment-related serious events, 6.1%) and no participant who met the prespecified composite of major device-related complications.[1][2]
Hematuria was the most frequent event (39/98, 40%, regardless of relatedness), followed by urinary tract infection (14/98, 14%), dysuria (9/98, 9.2%), urge or mixed incontinence (8/98, 8.2%), mild stress incontinence (7/98, 7.1%) and bladder spasm (6/98, 6.1%).[1] These were typically mild to moderate and resolved within 1 month. Treatment-related hematuria had a median time to resolution of 34 days, and serious hematuria from clot obstruction of the urethra or catheter became less frequent after mild-to-moderate Foley traction and bladder flushing were adopted.[1][2] Treatment-related urinary tract infection occurred in 11/98 (11.2%) versus 2/48 (4.2%) with sham, urethral stricture in 4/98 (4.1%) versus 1/48 (2.1%) and urinary retention in 3/98 (3.1%) versus 0/48.[1][2]
Ejaculatory dysfunction was reported as an adverse event in 4/98 (4.1%) versus 1/48 (2.1%) with sham (P > 0.9), and no treatment-related de novo erectile dysfunction was reported.[1] In the pharmacokinetic subset the mean maximum plasma paclitaxel concentration was 0.4 ng/mL.[1] In the 2-year report, no device- or treatment-related serious adverse events occurred after 12 months, and treatment-related hematuria affected 39/98 (39.8%), none needing transfusion.[3]
Limitations
The primary comparison paired 12-month results in the active arm with 3-month results in the sham arm, and the sham arm lost a substantial part of its early effect by 12 months. Sham participants were followed for 1 year, 20 of the 48 crossed over before then, and 26 had a 12-month sexual-function assessment; 2-year data are single-arm, with 2-year IPSS available for 74 of 100 men. Eligibility restricted the trial to prostates of 20 to 80 g with Qmax of 5 to 12 mL/s; men with a median lobe above 1 cm, an artificial sphincter, stents or prior pelvic radiation were excluded.[1][3] Urotronic, the manufacturer, was the sole funder. The authors state that the proposed mechanism, inhibition of smooth-muscle proliferation by paclitaxel, is inferred from established paclitaxel action and lacks direct evidence in this setting.[1][3]
In conversation
- Parallel to ROBUST III (2021). Same paclitaxel-coated balloon platform, tested in recurrent anterior urethral stricture rather than in BPH.
PINNACLE is the randomized sham-controlled trial on which the US approval of Optilume BPH rests, and the EAU states that randomized comparison with a reference technique is still required.[1][4] The device shares its paclitaxel-coated balloon platform with the urethral stricture balloon tested in ROBUST, but the two have separate indications.[1]
Guidelines and approvals
- AUA (BPH guideline, 2026), statement 50. Clinicians may offer an intraprostatic drug-coated balloon to patients with prostates of 20 to 80 cc and a prostatic urethral length of 32 to 55 mm without an obstructing median lobe .[5]
- EAU (Non-Neurogenic Male LUTS, March 2026 update). Lists paclitaxel-coated balloon dilatation (Optilume) among the non-ablative techniques under investigation and states that randomized trials comparing it with a reference technique are required; it makes no recommendation.[4]
- FDA (June 30, 2023). The Optilume BPH Catheter System was approved (PMA P220029) for the treatment of obstructive urinary symptoms associated with BPH in men 50 years or older.[2]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2023-08-09 | 12-month randomized comparison · primary | — | IPSS improvement from baseline, Optilume BPH at 12 months versus sham at 3 months, with a prespecified 25% super-superiority margin on the sham effect; difference = Optilume BPH minus sham with margin: 11.5 ± 7.8 points (n=100) vs 8.0 ± 8.3 points (n=48); difference 1.4; CI -1.6–4.5; P 0.178 Not met IPSS improvement without the margin, Optilume BPH at 12 months minus sham at 3 months: 11.5 ± 7.8 points vs 8.0 ± 8.3 points; difference 3.4; CI 0.6–6.2; P 0.008 Descriptive Mean percent IPSS improvement from baseline to 12 months in the Optilume BPH arm against a prespecified performance goal of 30%: 49% (95% CI 42.7% to 55.4%); P <0.001 Not tested Participants with at least 30% IPSS improvement, Optilume BPH at 12 months versus sham at 3 months: 76.6% (72/94) vs 52.1% (25/48); P 0.003 Not tested Qmax change from baseline, Optilume BPH at 12 months versus sham at 3 months; difference = Optilume BPH minus sham: +9.7 ± 10.1 mL/s (n=87) vs +5.5 ± 7.4 mL/s (n=43); difference 4.2; CI 0.8–7.6; P 0.009 Not tested Paired IPSS change from baseline at 12 months, Optilume BPH arm: -12.1 ± 7.5 points (paired n=89; 23.0 to 10.9); P <0.0001 Paired IPSS quality-of-life change from baseline at 12 months, Optilume BPH arm: -2.4 ± 1.9 points (paired n=89; 4.6 to 2.2); P <0.0001 Paired Qmax change from baseline at 12 months, Optilume BPH arm: +10.3 ± 10.2 mL/s (paired n=82; 8.7 to 19.0); +125.2%; P <0.0001 Paired postvoid residual change from baseline at 12 months, Optilume BPH arm: -25.2 ± 81.3 mL (paired n=82; 83.2 to 58.0); P 0.006 Sham-arm IPSS improvement from baseline at 12 months: 4.8 points (21.5%); — Descriptive IIEF erectile function domain change from baseline at 12 months: +0.9 ± 7.7 (n=87) vs +2.7 ± 7.1 (n=26); — MSHQ-EjD function score change from baseline at 12 months: +0.9 ± 3.5 (n=87) vs +0.2 ± 1.9 (n=26); — | Kaplan SA, Moss J, Freedman S, et al. "The PINNACLE Study: A Double-blind, Randomized, Sham-controlled Study Evaluating the Optilume BPH Catheter System for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia." *J Urol.* 2023;210(3):500-509. doi:10.1097/JU.0000000000003568 DOI |
| 2024-04-29 | 2-year follow-up · updated | — | At least 30% IPSS improvement without medical or surgical retreatment at 2 years; treatment failures counted in the denominator: 67.5% (56/83; 95% CI 56.3% to 77.4%); — Descriptive Paired IPSS change from baseline at 2 years: -12.1 ± 8.0 points (paired n=74; 23.0 to 11.0); P <0.0001 Descriptive Paired Qmax change from baseline at 2 years: +10.3 ± 15.9 mL/s (paired n=65; 8.7 to 19.0); P <0.0001 Descriptive Paired postvoid residual change from baseline at 2 years: -18.1 ± 100.2 mL (paired n=65; 84.0 to 65.9); P 0.151 Descriptive Paired BPH-II change from baseline at 2 years: -4.7 ± 3.7 points (paired n=74; 7.0 to 2.3); P <0.0001 Descriptive IIEF erectile function domain score at 2 years: 15.6 ± 10.3 (n=97) at baseline; 20.4 ± 10.2 (n=73) at 2 years; — Descriptive Surgical reintervention and added pharmacotherapy among the 100 randomized to Optilume BPH: Surgical 3/100 (3%); medication 6/100 (6%); — Descriptive | Kaplan SA, Moss JL, Freedman SJ. "Two-year long-term follow-up of treatment with the Optilume BPH catheter system in a randomized controlled trial for benign prostatic hyperplasia (the PINNACLE Study)." *Prostate Cancer Prostatic Dis.* 2024;27(3):531-536. doi:10.1038/s41391-024-00833-z DOI |
References
1. Kaplan SA, Moss J, Freedman S, et al. "The PINNACLE Study: A Double-blind, Randomized, Sham-controlled Study Evaluating the Optilume BPH Catheter System for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia." J Urol. 2023;210(3):500-509. doi:10.1097/JU.0000000000003568
2. US Food and Drug Administration. Optilume BPH Catheter System: Summary of Safety and Effectiveness Data (PMA P220029). 2023. FDA PDF
3. Kaplan SA, Moss JL, Freedman SJ. "Two-year long-term follow-up of treatment with the Optilume BPH catheter system in a randomized controlled trial for benign prostatic hyperplasia (the PINNACLE Study)." Prostate Cancer Prostatic Dis. 2024;27(3):531-536. doi:10.1038/s41391-024-00833-z
4. Cornu JN, Elterman D, Hashim H, et al. EAU Guidelines on Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS). European Association of Urology; March 2026 update. Section 5.3.5.c.2.
5. Goueli R, Badlani GH, Welliver C, et al. "Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA Guideline (2026)." American Urological Association; 2026.