The Zenflow Spring System Feasibility and Safety Study (ZEST)

The Zenflow Spring System Feasibility and Safety Study (ZEST)

This is a First in Human study to assess the feasibility, safety and effectiveness of the Zenflow Spring System in relieving the symptoms of obstructive Benign Prostatic Hyperplasia (BPH).

Study Overview

• Status: Unknown
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Device: Zenflow Spring System

Detailed Description

The purpose of the Zenflow Study is to evaluate the feasibility and safety of a novel prostatic urethral implant for the treatment of Lower Urinary Tract Symptoms (LUTS) that arise due to bladder outlet obstruction (BOO), secondary to the presence of Benign Prostatic Hypertrophy (BPH). Effectiveness will also be measured. It is intended that the features of the Zenflow Spring will provide an effective office-based treatment and management therapy for BPH with little or no side effects.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1407
    • MBAL "Tokuda Bolnitsa Sofia" AD
• New Zealand
  • Tauranga, New Zealand, 3140
    • Tauranga Urology Research Ltd
  • Nelson
    • Nelson South, Nelson, New Zealand, 7010
      • RoundHay Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. 50 to 80 years of age
2. Baseline IPSS score > 13, and a baseline Quality of Life (Qol) question score > 3
3. Prostate volume 25 - 80 cc by Trans Rectal Ultrasound (TRUS), measured within past 90 days
4. Anterior prostatic urethral length 2.5 - 4.0 cm by cystoscopy, as measured from bladder neck to verumontanum. TRUS will be accepted as a primary screening measure.
5. Failed or intolerant to medication regimen for the treatment of LUTS.

Exclusion Criteria:

New Zealand only: A maximum of 5 participants in acute or chronic urinary retention may be included in the study provided they meet other entry criteria. Exclusion exemptions for these patients are described in 4a, 5a and they are exempt from #6.

Participants will be excluded from participating in this trial if they meet any of the following criteria:

1. Obstructive median prostatic lobe or high bladder neck
2. Urethral stricture, meatal stenosis, or bladder neck obstruction - either current, or recurrent requiring 2 or more dilatations
3. Elevated Prostate Specific Antigen (PSA) (age 50-70 PSA ≥4; age 70+ PSA ≥6.5) unless negative biopsy within last 3 months, or a positive biopsy
4. Post-void residual volume (PVR) > 250 ml, if not in acute retention 4a. No maximum post void residual volume required if patient in acute or chronic urinary retention. (New Zealand Only, up to 5 patients)
5. Peak urinary flow rate > 12 ml/second, with ≥ 125 ml voided volume at baseline. 5a. No maximum urinary flow or minimum voided volume required if participant in acute or chronic urinary retention. (New Zealand Only, up to 5 patients)
6. History of chronic urinary retention. (New Zealand Only, up to 5 patients)
7. History of neurogenic bladder
8. Compromised renal function (e.g., serum creatinine > 1.8 mg/dl)
9. Concomitant Urinary Tract Infection (UTI)
10. Concomitant bladder stones
11. Confirmed or suspected prostate/bladder cancer
12. Previous pelvic irradiation or radical pelvic surgery
13. Previous prostate surgery, stent implantations, laser prostatectomy, hyperthermia or another invasive treatment to the prostate
14. Chronic prostatitis, or recurring prostatitis within the past 12 months
15. Serious concurrent medical conditions such as uncontrolled diabetes
16. Known allergy to nickel
17. Life expectancy less than 12 months
18. Use of concomitant medications (e.g., anticholinergics, antispasmodics or antidepressants) affecting bladder function
19. Anti-coagulant, anti-platelet, or thrombolytic medication other than Acetylsalicylic Acid (ASA) or Clopidogrel. ASA and Clopidogrel must be ceased 7 days prior to the procedure.
20. 5--reductase inhibitors within 6 months of pre-treatment evaluation unless evidence of same drug dose for at least 6 months with a stable voiding pattern (the drug dose should not be altered or discontinued for entrance into or throughout the study).
21. -blockers within 2 weeks of pre-treatment evaluation unless evidence of same drug dose for at least 6 months with a stable voiding pattern (the drug dose should not be altered or discontinued for entrance into or throughout the study).
22. Future fertility concerns
23. Any severe illness that might prevent study completion or would confound study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Receives intervention with the Zenflow Spring System.	Device: Zenflow Spring System; The Zenflow Spring is a nitinol urethral implant for the treatment of Lower Urinary Tract Symptoms (LUTS) that arise due to bladder outlet obstruction (BOO), secondary to the presence of Benign Prostatic Hypertrophy (BPH). The device is intended to be a permanent implant however it may be removed if necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Success defined as both 1) deliverability of the implant and 2) freedom from unanticipated adverse events (UAEs) not listed in the protocol or AEs that meet the protocol definition of Serious AEs.	Frequency of Device Success is assessed by subject, for both successful device placement in the target anatomy and absence of serious or unanticipated adverse events through discharge.	Intraoperative
Occurrence of device and/or procedure related Adverse Events as determined by investigator and independent medical reviewer	Frequency and severity of any device or procedure related adverse events, by subject.	Intraoperative
Occurrence of Adverse Event specific to indwelling catheterization, descriptive analysis	Frequency of indwelling catheterization = or > 7 days following placement of the investigational device.	Seven days following implantation of the investigational device
Effectiveness of implant measured through symptom improvement (International Prostate Symptom Score - IPSS)	Subjects should demonstrate improvement of > or = to 3 point reduction from baseline measurement.	3 months following device placement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Sexual Health using the Sexual Health in Men (SHIM) questionnaire	Observational assessment of subject scores on SHIM at the 6 months and 12 months visit, compared to baseline.	6 months, 12-,24-,36-, months post implantation
Assessment of Incontinence, using the Incontinence Severity Index (ISI) questionnaire	Observational assessment of subject scores on ISI at 2 weeks, 1 month and 3 months compared to baseline.	2 weeks, 1 month, 3 months
Observation of pain using a validated Visual Analogue Scale (VAS) questionnaire	Observational assessment of subject reports of pain on the VAS questionnaire, at discharge and follow up visits up to 3 months, compared to baseline.	through 3 month follow-up
Improvement in Uroflowmetry compared to baseline	Uroflowmetry is measured at 3 months post implantation and compared to baseline	3-, 6-, 12-, 24-, 36-months post implantation
Effectiveness of implant measured through symptom improvement (International Prostate Symptom Score - IPSS)	Observation of IPSS scores compared to baseline at 12 months follow up.	12 months 24 months and 36 months
Effectiveness of the treatment by assessing need for further treatment to alleviate symptoms of BPH.	Observation of incidence of repeat invasive treatment for LUTS through 12 months post-procedure	12 months 24 months and 36 months

Collaborators and Investigators

• Sponsor: Zenflow, Inc.

Publications and helpful links

General Publications

• Perry MJ, Roodhouse AJ, Gidlow AB, Spicer TG, Ellis BW. Thermo-expandable intraprostatic stents in bladder outlet obstruction: an 8-year study. BJU Int. 2002 Aug;90(3):216-23. doi: 10.1046/j.1464-410x.2002.02888.x.
• Charles J, Valenti L, Britt H. BPH - management in general practice. Aust Fam Physician. 2011 Oct;40(10):757.
• Woo HH, Gillman MP, Gardiner R, Marshall V, Lynch WJ. A practical approach to the management of lower urinary tract symptoms among men. Med J Aust. 2011 Jul 4;195(1):34-9. doi: 10.5694/j.1326-5377.2011.tb03185.x.
• Milani S, Djavan B. Lower urinary tract symptoms suggestive of benign prostatic hyperplasia: latest update on alpha-adrenoceptor antagonists. BJU Int. 2005 Jun;95 Suppl 4:29-36. doi: 10.1111/j.1464-410X.2005.05485.x.
• Schelin S, Geertsen U, Walter S, Spangberg A, Duelund-Jacobsen J, Kroyer K, Hjertberg H, Vatne V, Richthoff J, Nordling J. Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention: a prospective, randomized, controlled, multicenter study. Urology. 2006 Oct;68(4):795-9. doi: 10.1016/j.urology.2006.05.020.
• Bruskewitz RC, Larsen EH, Madsen PO, Dorflinger T. 3-year followup of urinary symptoms after transurethral resection of the prostate. J Urol. 1986 Sep;136(3):613-5. doi: 10.1016/s0022-5347(17)44991-3.
• Thomas JA, Tubaro A, Barber N, d'Ancona F, Muir G, Witzsch U, Grimm MO, Benejam J, Stolzenburg JU, Riddick A, Pahernik S, Roelink H, Ameye F, Saussine C, Bruyere F, Loidl W, Larner T, Gogoi NK, Hindley R, Muschter R, Thorpe A, Shrotri N, Graham S, Hamann M, Miller K, Schostak M, Capitan C, Knispel H, Bachmann A. A Multicenter Randomized Noninferiority Trial Comparing GreenLight-XPS Laser Vaporization of the Prostate and Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: Two-yr Outcomes of the GOLIATH Study. Eur Urol. 2016 Jan;69(1):94-102. doi: 10.1016/j.eururo.2015.07.054. Epub 2015 Aug 15.
• Reich O, Gratzke C, Bachmann A, Seitz M, Schlenker B, Hermanek P, Lack N, Stief CG; Urology Section of the Bavarian Working Group for Quality Assurance. Morbidity, mortality and early outcome of transurethral resection of the prostate: a prospective multicenter evaluation of 10,654 patients. J Urol. 2008 Jul;180(1):246-9. doi: 10.1016/j.juro.2008.03.058. Epub 2008 May 21.
• Mandeville J, Gnessin E, Lingeman JE. New advances in benign prostatic hyperplasia: laser therapy. Curr Urol Rep. 2011 Feb;12(1):56-61. doi: 10.1007/s11934-010-0153-1.
• Ahyai SA, Lehrich K, Kuntz RM. Holmium laser enucleation versus transurethral resection of the prostate: 3-year follow-up results of a randomized clinical trial. Eur Urol. 2007 Nov;52(5):1456-63. doi: 10.1016/j.eururo.2007.04.053. Epub 2007 Apr 25.
• Bachmann A, Tubaro A, Barber N, d'Ancona F, Muir G, Witzsch U, Grimm MO, Benejam J, Stolzenburg JU, Riddick A, Pahernik S, Roelink H, Ameye F, Saussine C, Bruyere F, Loidl W, Larner T, Gogoi NK, Hindley R, Muschter R, Thorpe A, Shrotri N, Graham S, Hamann M, Miller K, Schostak M, Capitan C, Knispel H, Thomas JA. 180-W XPS GreenLight laser vaporisation versus transurethral resection of the prostate for the treatment of benign prostatic obstruction: 6-month safety and efficacy results of a European Multicentre Randomised Trial--the GOLIATH study. Eur Urol. 2014 May;65(5):931-42. doi: 10.1016/j.eururo.2013.10.040. Epub 2013 Nov 11.
• Gao YA, Huang Y, Zhang R, Yang YD, Zhang Q, Hou M, Wang Y. Benign prostatic hyperplasia: prostatic arterial embolization versus transurethral resection of the prostate--a prospective, randomized, and controlled clinical trial. Radiology. 2014 Mar;270(3):920-8. doi: 10.1148/radiol.13122803. Epub 2013 Nov 13.
• Bouza C, Lopez T, Magro A, Navalpotro L, Amate JM. Systematic review and meta-analysis of Transurethral Needle Ablation in symptomatic Benign Prostatic Hyperplasia. BMC Urol. 2006 Jun 21;6:14. doi: 10.1186/1471-2490-6-14.
• Roehrborn CG, Rukstalis DB, Barkin J, Gange SN, Shore ND, Giddens JL, Bolton DM, Cowan BE, Cantwell AL, McVary KT, Te AE, Gholami SS, Moseley WG, Chin PT, Dowling WT, Freedman SJ, Incze PF, Coffield KS, Borges FD, Rashid P. Three year results of the prostatic urethral L.I.F.T. study. Can J Urol. 2015 Jun;22(3):7772-82.
• Peyton CC, Badlani GH. The management of prostatic obstruction with urethral stents. Can J Urol. 2015 Oct;22 Suppl 1:75-81.
• Oesterling JE. A permanent, epithelializing stent for the treatment of benign prostatic hyperplasia. Preliminary results. J Androl. 1991 Nov-Dec;12(6):423-8.
• Shore ND, Dineen MK, Saslawsky MJ, Lumerman JH, Corica AP. A temporary intraurethral prostatic stent relieves prostatic obstruction following transurethral microwave thermotherapy. J Urol. 2007 Mar;177(3):1040-6. doi: 10.1016/j.juro.2006.10.059.
• Yildiz G, Bahouth Z, Halachmi S, Meyer G, Nativ O, Moskovitz B. Allium TPS--A New Prostatic Stent for the Treatment of Patients with Benign Prostatic Obstruction: The First Report. J Endourol. 2016 Mar;30(3):319-22. doi: 10.1089/end.2015.0593. Epub 2015 Nov 17.
• Song HY, Kim CS, Jeong IG, Yoo D, Kim JH, Nam DH, Bae JI, Park JH. Placement of retrievable self-expandable metallic stents with barbs into patients with obstructive prostate cancer. Eur Radiol. 2013 Mar;23(3):780-5. doi: 10.1007/s00330-012-2650-8. Epub 2012 Sep 16.
• Armitage JN, Cathcart PJ, Rashidian A, De Nigris E, Emberton M, van der Meulen JH. Epithelializing stent for benign prostatic hyperplasia: a systematic review of the literature. J Urol. 2007 May;177(5):1619-24. doi: 10.1016/j.juro.2007.01.005.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 30, 2016

Study Record Updates

• Last Update Posted (Actual): February 6, 2019
• Last Update Submitted That Met QC Criteria: February 4, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia
• Other Study ID Numbers: CLIN-0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided