Safety and Effectiveness Study of the Zenflow Spring System

Not Applicable

Active, not recruiting

• Conditions: BPH (Benign Prostatic Hyperplasia); Lower Urinary Tract Symptoms (LUTS)
• Interventions: Device: Zenflow Spring System; Device: Sham Procedure

• Registration Number: NCT04987138
• Lead Sponsor: Zenflow, Inc.

Brief Summary

Evaluate the safety and effectiveness of the Zenflow Spring System in relieving LUTS associated with BPH.

Detailed Description

Prospective, multi-center, multinational, 2:1 randomized, single-blinded, controlled clinical trial of the Zenflow Spring System.

Patients randomized to the treatment group will undergo Zenflow Spring placement.

Patients randomized to the control group will undergo a Sham procedure. Patients and site personnel administering follow-up assessments will be blinded to the randomized treatment through completion of the 3-month follow-up visit. Once a patient has completed their 3-month follow-up assessments, they will be unblinded. Following unblinding, patients who received a Sham procedure may elect to receive treatment with the Zenflow Spring System or alternatively they may exit the study.

The duration of study participation is 60 months for patients who receive a Spring Implant and 3 months for subjects in the Control Arm.

Study Timeline

• Study First Submitted: 2021-07-13
• Study First Submitted QC: 2021-07-22
• Study First Posted: 2021-08-03
• Study Start: 2021-09-30
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-11
• Primary Completion: 2024-06-30
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 279

Inclusion Criteria

1. Subject is able and willing to comply with all the assessments of the study,
2. Subject or subject's legal representative has been informed of the nature of the study, agrees to participate and has signed the informed consent form,
3. ≥ 45 years of age,
4. Baseline IPSS score ≥ 13; ≥ 1 in the IPSS voiding to storage sub-score ratio (IPSS-V/S),
5. Prostate volume 25 - 80 cc by transrectal ultrasound (TRUS), measured within 120 days post study consent,
6. Prostatic urethral length between 25 and 45 mm, as measured by cystoscopic pull-back,
7. Failed, intolerant, or subject choice to not take a medication regimen for the treatment of LUTS.

Exclusion Criteria

1. Obstructive intravesical median prostatic lobe as determined by ultrasound (i.e., more than 10 mm intravesical prostatic protrusion on sagittal mid-prostate plane via abdominal ultrasound),

2. High bladder neck with the absence of lateral lobe encroachment indicating a high likelihood of primary bladder neck obstruction as determined by the Investigator,

3. Urethral stricture, meatal stenosis, or bladder neck stricture - either current or recurrent,

4. Anatomical anomalies that will not accommodate the Implant, as determined by cystoscopy (e.g., prostatic urethral length to height geometry),

5. Requires indwelling catheter or intermittent catheterization to void,

6. Baseline PSA > 10 ng/mL or confirmed or suspected prostate cancer (Subjects with a PSA level above 2.5 ng/mL, or age specific, or local reference ranges should have prostate cancer excluded to the Investigator's satisfaction),

7. One of the following baseline test results, taken from a single uroflowmetry reading:

   1. Urinary volume void ≤ 125mL (pre-bladder urinary volume of ≥ 150 mL required),
   2. Peak urinary flow rate (Qmax) of ≤ 5 ml/second or > 15 mL/second,
   3. Post- void residual volume (PVR) > 250 mL

8. History of other diseases causing voiding dysfunction including urinary retention (e.g., uncontrolled diabetes, diagnosis of neurogenic bladder, Parkinson's disease, multiple sclerosis, etc.),

9. Subjects with overactive bladder in the absence of benign prostatic obstruction,

10. Acute urinary tract infection (UTI) or finding of asymptomatic bacteriuria (Note: subject can be enrolled if the UTI is treated and followed with a negative urine test result), or subjects with history of recurrent UTIs (defined as > 3 UTIs in the past 12 months),

11. Concomitant bladder stones,

12. Previous pelvic irradiation or radical pelvic surgery,

13. Previous prostate surgery, including: enucleation, resection, vaporization, thermotherapy, ablation, stenting or prostatic urethral lift,

14. Chronic prostatitis, recurrent prostatitis, chronic pelvic pain syndrome (CPPS), or painful bladder syndrome within the past 12 months

15. Known allergy to nickel,

16. Life expectancy less than 60 months,

17. Use of concomitant medications (e.g., anticholinergics, antispasmodics or tricyclic antidepressants) affecting bladder function,

18. Inability to stop taking anticoagulants and/or antiplatelets for at least 3 days prior to the procedure or coumadin for at least 5 days prior to the procedure (Note: low dose aspirin therapy (81 mg) is permitted),

19. Taking 5-alpha-reductase inhibitors within 3 months of baseline evaluation,

20. Taking one of the following within 2 weeks of baseline evaluation:

    1. alpha-blockers,
    2. imipramine,
    3. anticholinergics,
    4. cholinergic gonadotropin releasing hormonal analogues,
    5. Phosphodiesterase-5 Enzyme Inhibitors (Tadalafil) in doses for BPH,
    6. Beta-3 adrenergic receptor agonist (Mirabegron),

21. Taking androgens, unless eugonadal state for at least 3 months or greater as documented by the Investigator,

22. Taking one of the following within 24 hours of pre-treatment (baseline) evaluation:

    1. phenylephrine, or,
    2. pseudoephedrine,

23. Future fertility concerns, or,

24. In the Investigator's opinion, the subject has a physical, psychological, or medical impairment that might prevent study completion or would confound study results (including subject questionnaires).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Crossover Cohort	Zenflow Spring System	Control Arm (Sham) patients can receive treatment with the Zenflow Spring System after their 3-month follow-up assessments are completed, and their symptoms warrant treatment and enrollment criteria are met. The study visit follow-up schedule will restart and the subject will be followed for 60 months post Zenflow Spring implantation. Unless treated with the Spring System, the subject will be exited from the study once they have completed their 3-month follow-up visit.
Control Arm	Sham Procedure	Includes all patients who receive a sham procedure. Patients will be shielded from the treatment area and cystoscopy screen. A Foley Catheter is placed into the patient's bladder and inflated. Additionally, devices will be used to produce mock deployment sounds of the Zenflow procedure. Once complete, the balloon will be deflated and the catheter will be removed, completing the procedure. Control arm subjects are followed for 3 months and exited from the study unless they elect and qualify for Crossover.
Roll-in Cohort	Zenflow Spring System	Each Investigator will be allowed to treat up to 3 roll-in subjects with the Spring Implant prior to initiation of randomization. Roll-in patients will be followed for 60 months.
Treatment Arm	Zenflow Spring System	Includes all patients who are randomized and start the treatment procedure. During the procedure the patient will be shielded from the treatment area and cystoscopy screen. The patient and site personnel administering follow-up assessments will be blinded to the study arm through the 3-month follow-up visit. Unblinding will occur at 3 months post-procedure after the assessments are completed. Follow up will continue for 60 months.

Primary Outcome Measures

Name	Time	Method
Effectiveness of the Spring Implant in reducing symptoms of Benign Prostatic Hyperplasia (BPH) as compared to Sham	Procedure to 3 months	The Treatment Arm will be considered superior to the Control Arm (Sham) when the mean 3-month improvement from baseline score for the IPSS symptom questionnaire demonstrates a minimum statistical margin of 25% compared to mean improvement from baseline for the Control Arm (Sham) alone.
Effectiveness- Symptoms Improvement	Procedure to 12 months	The mean percent change in IPSS in the treatment arm is at least 30% improvement over the Patient's pre-treatment baseline score.
Safety - Adverse Events	Procedure through 12 months	The rate of device or procedure related serious adverse events in both the Treatment Arm and the Sham Arm.
Safety - The need for urinary catheterization	Greater than 7 days after procedure	The rate of extended post-operative urinary catheterization (\> 7 days from treatment) for inability to void among patients treated with the Zenflow Spring System.

Secondary Outcome Measures

Name	Time	Method
Safety - Sexual Health Questionnaire 1	3 months post procedure through 24 months post procedure	Change in sexual health characterized by the questionnaire Sexual Health Inventory for Men (SHIM).
Safety - Adverse Events	Procedure through 60 months	Rate of device or procedure related adverse events at all time points.
Effectiveness - long term symptom improvement 2	Procedure through 60 months	Mean percent change in IPSS in the treatment arm compared to baseline at all timepoints other than the primary endpoints.
Effectiveness - flow metrics	1 month post procedure through 60 months	Change from baseline in uroflowmetry measures of peak flow rate (Qmax)
Safety - Device Removal	Procedure through 60 months	Assessment of adverse events outcomes related to a Spring Implant removal procedure.
Safety - Pain Assessment Questionnaire	Procedure through 3 months	Comparison of pain at discharge to 2-week, 1- and, 3-month follow-up visits per Visual Analogue Scale (VAS) questionnaire. The VAS questionnaire asks the patient to indicate on a scale of 1 to 10 his level of pain where 1 is no pain and 10 is the worst pain.
Safety - Sexual Health Questionnaire 2	3 months post procedure through 24 months post procedure	Change in sexual health characterized by questionnaire Male Sexual Health Questionnaire - Ejaculatory Domain (MSHQ-EjD)
Effectiveness - long term symptom improvement 1	Procedure through 12 months	Percent of patients who experience at least a 30 percent improvement in IPSS from their baseline pre-treatment score
Safety - Classification of Adverse Events	Procedure through 3 months	Proportion of patients with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability
Effectiveness - Re-intervention (device)	Procedure through 60 months	Post-procedure incidence of secondary reintervention using an alternate surgical LUTS therapy.
Effectiveness - Re-intervention (drug)	Procedure through 60 months	Post-procedure incidence of secondary reintervention using standard pharmacological agents for LUTS therapy.

Trial Locations

Locations (7)

Northshore University Health System; 🇺🇸 Glenview, Illinois, United States

American Institute of Research; 🇺🇸 Los Angeles, California, United States

Sheldon Freedman, MD, LTD; 🇺🇸 Las Vegas, Nevada, United States

Carolina Urologic Research Associates; 🇺🇸 Myrtle Beach, South Carolina, United States

Urology of Virginia, PLLC; 🇺🇸 Virginia Beach, Virginia, United States

Midtown Urology Associates; 🇺🇸 Austin, Texas, United States

Urology Austin, PLLC; 🇺🇸 Austin, Texas, United States