Chughtai 2020.

Study characteristics
Methods	Study design: prospective, randomized parallel study. Study dates: July 2015 and October 2018 Setting: outpatient, multicenter, international Country: United States and Canada
Participants	Inclusion criteria: men with: Men aged 50 and above with symptomatic BPH. IPSS symptom severity score ≥ 10 Peak urinary flow of < 12 mL/sec. Meeting the criterion on two separate voiding trials, on a minimum voided volume of at least 125 cc for each voiding trial. Prostate volume between 25 mL to 75 mL (assessed by ultrasound) Blood CBC and biochemistry up to two weeks before screening demonstrating: Normal values of the PT, PTT, and INR tests (anticoagulants should be stopped according to GCP) Subject able to comply with the study protocol and signed informed consent Normal Urinalysis and urine culture Exclusion Criteria: Cardiac arrhythmias, cardiac disease including congestive heart failure, uncontrolled diabetes mellitus, significant respiratory disease, or known immunosuppression; Neurogenic bladder and/or sphincter abnormalities due to Parkinson's disease, multiple sclerosis, cerebral vascular accident, diabetes A post void residual (PVR) volume > 250 mL measured by ultrasound or acute urinary retention Compromised renal function (i.e., serum creatinine level > 1.8 mg/dl, or upper tract disease); Confirmed or suspected bladder cancer; Recent (within 3 months) cystolithiasis or hematuria; Urethral strictures, bladder neck contracture, urinary bladder stones or other potentially confounding bladder pathology; An active urinary tract infection. Enrolled in another treatment trial for any disease within the past 30 days. Previous colorectal surgery (other than hemorrhoidectomy) or history of rectal disease if the therapy may potentially cause injury to sites of previous rectal surgery, e.g., if a transrectal probe is used; Previous pelvic irradiation, cryosurgery or radical pelvic surgery; Previous prostate surgery, balloon dilatation, stent implantation, laser prostatectomy, hyperthermia, or any other invasive treatment to the prostate History of prostatitis within the past 5 years. Median lobe obstruction of the prostate. Cancer that is not considered cured, except basal cell or squamous cell carcinoma of the skin (cured defined as no evidence of cancer within the past 5 years). Any serious medical condition likely to impede successful completion of the study Participating in any other investigational study for either drug or device which can influence collection of valid data under this study. Subjects who are actively taking medications that affects urination and BPH symptoms not completing the required washout period. Baseline PSA ≥ 10 ng/mL. Positive DRE. Baseline PSA between 2.5‐10 ng/mL and free PSA < 25%, without a subsequent negative prostate biopsy. Total number of participantsrandomized: 185 Group 1: n = 128 temporarily implanted nitinol device (iTIND) Age (years), mean (SD): 61.5 (6.5) BMI, mean (SD): 28.8 (5.7) Comprehensive Complication Index (CCI), mean (SD): 2.52 (1.6) Prostate Volume, mean (SD): 43.4 (15.5) IPSS, mean (SD): 22.1 (6.8) Qmax, mean (SD): 8.7 (3.3) Postvoid Residual Volume (PVR) m, mean (SD): 61.6 (55.5) QoL, mean (SD): 4.6 (1.3) PSA, mean (SD): 2.2 (2.3) Internation Index of Erectile Function (IIEF), mean (SD): 38.3 (20.7) Sexual Health Inventory For Men (SHIM), mean (SD): 13.2 (7.3) Group 2: n = 57 Sham control Age (years), mean (SD): 60.1 (6.3) BMI, mean (SD): 28.8 (5.5) Comprehensive Complication Index (CCI), mean (SD): 1.26 (0.7) Prostate Volume, mean (SD): 43.8 (13.3) IPSS, mean (SD): 22.8 (6.2) Qmax, mean (SD): 8.5 (2.4) Postvoid Residual Volume (PVR) mL, mean (SD): 61.9 (54.2) QoL, mean (SD): 4.9 (1) PSA, mean (SD): 1.8 (1.8) Internation Index of Erectile Function (IIEF), mean (SD): 39.1 (19.6) Sexual Health Inventory For Men (SHIM), mean (SD): 14.2 (6.6)
Interventions	Group 1 (n = 128): “the iTind device is comprised of three elongated, intertwined nitinol struts at the 12, 5, and 7 o’clock positions, an anti‐migration anchoring leaflet at 6 o’clock, and a polyester retrieval suture for easy device removal. The device is implanted for 5‐7 days, during which it expands and exerts radial force, creating deep ischemic incisions, and a remodeling on the prostate tissue at the bladder neck and anterior prostatic fossa. The iTind is deployed under direct visualization in an ambulatory procedure using a rigid cystoscopy. The device is removed through either a rigid cystoscope or an open ended 22F Foley catheter with topical anaesthesia. Both implantation and removal can be done under local, IV, or general anaesthesia at the discretion of the performing physician. Catheterisation is not required following either implantation or removal.” Group 2 (n = 57): “The sham control was the insertion and removal of an 18F silicon Foley catheter in order to simulate both the implantation and retrieval procedures. Throughout the procedure, the surgeon gave verbal description as if deploying the iTind device, after which the catheter was removed. A similar protocol was followed for the removal. Although the iTind device is deployed through a rigid cystoscope, a Foley catheter was used to minimize the risk of procedure‐related morbidity.” Co‐interventions: Subjects in both the device and control groups were draped to prevent them from seeing the treating physician and the device.
Outcomes	Urologic symptom scores How measured: IPSS score change from baseline Time points measured: baseline, 1.5 and 3 months Time points reported: baseline, 1.5, 3 (blinded) and 12 months (unblinded) Subgroups: none Quality of life How measured: not reported Time points measured: baseline, 1.5 and 3 months Time points reported: baseline, 1.5, 3, and 12 months (unblinded) Subgroups: none Acute urinary retention How measured: number of patients developing acute urinary retention Time points measured: not reported Time points reported: not reported Subgroups: none Erectile function How measured: IIEF and SHIM score Time points measured: baseline, 1.5 and 3 months Time points reported: not reported. Subgroups: none Retreatment How measured: Number of participants that received additional treatment Time points measured: baseline and 1 year Time points reported: baseline and 1 year (global, not by group) Subgroups: none Minor and major adverse event (including ejaculatory/erectile dysfunction/urinary retention) How measured: National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0 Time points measured: not reported Time points reported: not reported Subgroups: none Relevant outcomes not reported in this study: Indwelling urinary catheter (none of the participants required a catheter)
Funding sources	Medi‐Tate Ltd. sponsored this study.
Declarations of interest	Bilal Chughtai, MD is a consultant for Medi‐Tate Ltd, Olympus, Boston Scientific, and Medeon Bio.
Notes	The study was unblinded at three months follow‐up. Contact info: Bilal Chughtai, E‐mail: bic9008@med.cornell.edu Protocol: trial registry (NCT02506465) Language of publication: English
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Subjects were randomized in 2:1 ratio to either iTind or control groups using permuted blocks stratified by center by using a central electronic data program.” The investigators describe a random component in the sequence generation process.
Allocation concealment (selection bias)	Low risk	Quote: “Subjects were randomized in 2:1 ratio to either iTind or control groups using permuted blocks stratified by center by using a central electronic data program.” Participants and investigators enrolling participants could not foresee assignment.
Blinding of participants and personnel (performance bias) Subjective outcomes	Low risk	Subjective outcomes
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	Participants were blinded. Quote: “This prospective, randomized, controlled, single blinded study of the second‐generation iTind procedure...”
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Participants were blinded. These outcomes are unlikely to be affected by blinding. Quote: “This prospective, randomized, controlled, single blinded study of the second‐generation iTind procedure...”
Incomplete outcome data (attrition bias) Urologic symptom scores/Quality of life	High risk	Quote: Outcome data provided by the authors at 3 months: 84/128 intervention group and 40/57 in the sham group.
Incomplete outcome data (attrition bias) Major adverse events/minor adverse events	High risk	The authors state that 13/118 (11%) and 10/57 (17%) were lost to follow‐up at 3 months. Unbalanced attrition. This analysis was not imputed.
Incomplete outcome data (attrition bias) Retreatment	High risk	The authors state that 13/118 (11%) and 10/57 (17%) were lost to follow‐up at 3 months. Unbalanced attrition. This analysis was not imputed.
Incomplete outcome data (attrition bias) Erectile function	High risk	The authors state that 13/118 (11%) and 10/57 (17%) were lost to follow‐up at 3 months. Unbalanced attrition. This analysis was not imputed.
Incomplete outcome data (attrition bias) Ejaculatory function	High risk	The authors state that 13/118 (11%) and 10/57 (17%) were lost to follow‐up at 3 months. Unbalanced attrition. This analysis was not imputed.
Incomplete outcome data (attrition bias) Acute urinary retention	High risk	The authors state that 13/118 (11%) and 10/57 (17%) were lost to follow‐up at 3 months. Unbalanced attrition. This analysis was not imputed.
Selective reporting (reporting bias)	Unclear risk	The study registry only specified two outcomes at three months (IPSS and “secondary safety”). We wrote to the study author for more information.
Other bias	Low risk	No other sources of bias were detected.