Early Feasibility Trial Research Articles

Effectiveness and safety of a novel, collapsible pessary for management of pelvic organ prolapse

Pessaries are an effective treatment for pelvic organ prolapse, yet currently available pessaries can cause discomfort during removal and insertion. An early feasibility trial of an investigational, collapsible pessary previously demonstrated mechanical feasibility during a brief 15-minute office trial. Longer-term, patient-centered safety and efficacy data are needed. This study aimed to assess the effectiveness and safety of the investigational vaginal pessary for pelvic organ prolapse at 3 months. This was a prospective, 7-center, open-label equivalence study with participants serving as their own controls. Subjects were current users of a Gellhorn or ring pessary with ≥stage 2 prolapse. Subjective and objective data were collected at baseline for 1 month while subjects used their current pessary. Data were then collected throughout a 3-month treatment phase with the study pessary. The primary outcome was change in Pelvic Floor Distress Inventory-20 score. Secondary outcome measures included objective assessment of prolapse support, changes in the Pelvic Floor Impact Questionnaire-7, and pain with insertion and removal, measured using a visual analog scale. Data from subjects fitted with the study pessary were analyzed using an intention-to-treat approach, and those who dropped out were assigned scores at the upper limit of the predefined equivalence limits. Secondary per protocol analyses included subjects who completed treatment. The study was powered to 80% with a minimal important change equivalence limit of 18.3 points on the Pelvic Floor Distress Inventory-20 scale. Square root transformations were used for nonparametric data, and P values were adjusted for multiple comparisons. A total of 78 subjects were enrolled, however, 16 withdrew before study pessary placement. The study pessary was fitted in 62 subjects (50 ring and 12 Gellhorn pessary users), and 48 (62%) completed the 3-month intervention. The change in Pelvic Floor Distress Inventory-20 scores at 3 months demonstrated equivalence when compared with the subjects' baseline scores (mean difference,-3.96 [improvement]; 90% confidence interval,-11.99 to 4.08; P=.002). Among those completing study, the Pelvic Floor Distress Inventory-20 scores, equivalence was not demonstrated and scores favored the study pessary (mean difference,-10.45; 90% confidence interval,-20.35 to 0.54; P=.095). Secondary outcomes included objective measures of support, which were similar (mean difference: Ba, 0.54 cm; Bp, 0.04 cm, favoring study pessary; improvement in mean Pelvic Floor Impact Questionnaire-7 scores for those who completed the trial: before, 32.23; after, 16.86; P=.019), and pain with insertion and removal, which was lower with the study pessary than with the subject's own pessary (mean difference visual analog scale score insertion, 9.91 mm; P=.019; removal, 11.23 mm; P=.019). No serious adverse events related to the pessary were reported. Equivalence was demonstrated in the primary outcome of the study pessary when compared with current, noncollapsible pessaries in terms of change in severity and bother of pelvic floor symptoms. Among participants who completed the trial, the Pelvic Floor Impact Questionnaire-7 improved with study pessary use and change in Pelvic Floor Distress Inventory-20 scores were nonequivalent, favoring the study pessary. Subjects reported significantly lower pain scores with both pessary insertion and removal with the novel collapsible pessary when compared with their standard pessary.

Long-term structural right heart remodeling following transcatheter annuloplasty for treating severe tricuspid regurgitation assessed by CT scan

Abstract Background Transcatheter tricuspid annuloplasty has emerged as an attractive percutaneous therapy for patients with severe symptomatic tricuspid regurgitation. Cardioband (Edwards) was the first dedicated CE marked percutaneous device for tricuspid regurgitation. Despite mid-long-term clinical safety and efficacy demonstrated in early feasibility trials and registries, there is no data about its impact on right heart structural remodeling using computed tomography (CT). Our aim was to assess right heart remodeling and changes in the tricuspid annulus (TA) one year after Cardioband implantation. Methods A total of 30 patients were prospectively included in the study; 21 of them had baseline and at least 1-year follow-up CT analysis. The average time from the basal CT scan and the procedure was 118±136 days, and from the intervention to follow-up CT scan was 468±251 days. 2D and 3D analyses were performed with 3mensio version 10.3 at baseline and at least 12 months after Cardioband implantation. Results There was a significant decrease in right ventricular dimensions at follow-up (right ventricular basal diameter was 53.65 ± 8.45 mm at baseline Vs 48.54 ± 9.12 mm at 1-year follow-up; right ventricular mid cavity diameter was 40.30 ± 9.10 mm at baseline Vs 34.22 ± 9.22 at the end of follow-up, and right ventricular longitudinal diameter was 75.43 ± 9.85 mm at baseline Vs 69.95 ± 9.96 mm at the end of follow-up, all of them were statistically significant). A reduction in right atrial dimension was also observed (longitudinal diameter 66.86 ± 7.63 mm at baseline Vs 64.89 ± 9.99 mm at the end of follow-up; transverse diameter of 61.62 ± 8.38 mm at baseline Vs 60.59 ± 8.3 mm at the end of follow-up, p<0.001). There was a significant decrease in the area and diameters of the dilated TA (area at baseline 16.51 ± 3.06 cm2 vs 8.90 ± 2.71 cm2 at the end of follow-up, p=0.02; septolateral diameter 45.42 ± 5.02 mm at baseline vs 33.87 ± 5.09 mm at the end of follow-up, p=0.01). Conclusions Long-term favorable right ventricular chambers and TA remodeling was observed following Cardioband implantation assessed by CT scan. This finding could explain the long-term clinical benefit demonstrated in feasibility studies.Right heart remodeling after Cardioband

107-LB: Clinical Performance of Extended Mio 30 Infusion Set

Objective: Medtronic Mio™ 30 infusion set (M30IS) is a single use IS for pump users with pre-loaded inserter, a 30° insertion angle, and labeled for 3-day use. The M30IS wear duration is impacted by initial local trauma caused by insertion and sustained inflammation by cannula & insulin infusion (insulin aggregates & other impurities in the infusate), with the latter being predominant. An extended Mio™ 30 infusion set (EM30IS) was developed by improving insulin formulation stability in the fluid path. This study reports on the performance of the EM30IS in persons with T1D during an early feasibility trial (ClinicalTrials.gov: NCT05544643). Method: This is a X over study of EM30IS and M30IS on 21 subjects with type 1 diabetes. Each subject wore both sets 4-5 times each on a preferred site that was continuously infused with insulin lispro or aspart subcutaneously via a Medtronic 780G pump for 3 days (M30IS), 7 days (EM30IS) or until failure. Endpoints of safety and effectiveness (failure rate due to unexplained hyperglycemia <16%) were evaluated. Exploratory analyses related to performance and glycemic control were also evaluated. Results: The EM30IS survival rate at 6 days (70%) was comparable to M30IS survival rate at 3 days (63%). Glycemic control outcomes were equivalent (see Table 1) and there were no episodes of EM30IS-related severe hypoglycemia or DKA. Conclusion: The EM30IS was safe and its performance at 6 days was equivalent to the performance of M30IS at 3 days. Disclosure O. Cohen: Employee; Medtronic. Y. Cohen: None. S. Chattaraj: Employee; Medtronic. G. Zhang: Employee; Medtronic. E. Anselmo: Employee; Medtronic. A. Tirosh: Advisory Panel; Medtronic. Research Support; Medtronic. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Funding Medtronic

Endovascular Management of the Ascending Aorta: State of the Art.

Endovascular stent graft repair (EVAR) has revolutionized the management of aneurysms and dissections of the thoracic and abdominal aorta and is considered the first-line treatment in such pathologies. Initially designed for patients unfit for open repair, EVAR and thoracic endovascular aortic stent graft repair are associated with improved morbidity and mortality and a faster recovery process. The endovascular revolution of the aorta continues moving proximally, with fenestrated and branch stent grafts currently in clinical trials for the management of thoracoabdominal aortic aneurysms, and several branched thoracic devices are either approved or in trial for management of aortic arch pathologies. The final frontier in the endovascular management of the aorta is the aortic root and ascending aorta. The first early feasibility trial for management of type A aortic dissection has recently concluded with a multicenter phase 2 study slated for the spring of 2023. The following article updates the reader on the unique challenges of endovascular management of the ascending aorta and a look at the future technologies that will define this space.

Emergency department initiated resuscitative endovascular balloon occlusion of the aorta (REBOA) for out-of-hospital cardiac arrest is feasible and associated with improvements in end-tidal carbon dioxide.

ObjectivesOut‐of‐hospital cardiac arrest (OHCA) claims the lives of approximately 350,000 people in the United States each year. Resuscitative endovascular balloon occlusion of the aorta (REBOA) when used as an adjunct to advanced cardiac life support may improve cardio‐cerebral perfusion. Our primary research objective was to determine the feasibility of emergency department (ED)‐initiated REBOA for OHCA patients in an academic urban ED.MethodsThis was a single‐center, single‐arm, early feasibility trial that used REBOA as an adjunct to advanced cardiac life support (ACLS) in OHCA. Subjects under 80 years with witnessed OHCA and who received cardiopulmonary rescuitation (CPR) within 6 minutes were eligible.ResultsFive patients were enrolled between February 2020 and April 2021. The procedure was successful in all patients and 4 of 5 (80%) patients had transient return of spontaneous circulation (ROSC) after aortic occlusion. Unfortunately, all patients re‐arrested soon after intra‐aortic balloon deflation and none survived to hospital admission. At 30 seconds post‐aortic occlusion, investigators noted a statistically significant increase in end tidal carbon dioxide of 26% (95% confidence interval, 10%, 44%).ConclusionInitiating REBOA for OHCA patients in an academic urban ED setting is feasible. Aortic occlusion during chest compressions is temporally associated with improvements in end tidal carbon dioxide 30 seconds after aortic occlusion. Four of 5 patients achieved ROSC after aortic occlusion; however, deflation of the intra‐aortic balloon quickly led to re‐arrest and death in all patients. Future research should focus on the utilization of partial‐REBOA to prevent re‐arrest after ROSC, as well as the optimal way to incorporate this technique with other endovascular reperfusion strategies.

V14-03 TRANSURETHRAL WATER VAPOR ABLATION (STEAM) TO TREAT LOCALIZED PROSTATE CANCER (INVESTIGATIONAL USE ONLY)

You have accessJournal of UrologyProstate Oncology II & Testis Oncology & Misc. Oncology (V14)1 Sep 2021V14-03 TRANSURETHRAL WATER VAPOR ABLATION (STEAM) TO TREAT LOCALIZED PROSTATE CANCER (INVESTIGATIONAL USE ONLY) Christopher Dixon, and Christopher Warlick Christopher DixonChristopher Dixon More articles by this author , and Christopher WarlickChristopher Warlick More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002111.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Convective water vapor is a unique technology that uses the thermal energy of water vapor (steam) to ablate tissue. The objective was in vivo validation of Transurethral Vapor Ablation (TUVA) in men with clinically significant localized prostate cancer by; Group 1 - TUVA/RRP assessed by immediate whole mount sectioning, Group 2 - TUVA assessed by pre/post treatment MRI in an early feasibility trial and Both Groups by intraoperative real-time ultrasound and AE assessment. METHODS: A tabletop generator and a transurethral endoscopic delivery device, along with real-time TRUS, were used to direct water vapor into any anatomic zone of the prostate to ablate malignant prostate tissue. The procedure technique currently used, including the endoscopic and real-time ultrasound monitoring of needle deployment, advancement and vapor delivery is demonstrated. To evaluate the convective principles of TUVA, real-time ultrasound patterns of vapor delivery and 7-day post treatment gadolinium MRI images were studied. Ablation effectiveness was assessed in two independent groups. In Group 1 by whole mount sectioning immediately following TUVA / radical prostatectomy. In Group 2 by assessing pre- and 7-day post TUVA MRI nonenhancement patterns as well as PIRADSv2 resolution. Immediate safety was assessed by intraoperative inspection, gross examination of the prostate (Group 1) and immediate post op adverse events along with 7-day MRI’s (Group 2). RESULTS: Real-time ultrasound vapor patterns confirmed convective spread within the zonal anatomy and boundaries of the prostate. Real-time ultrasound during treatment demonstrated the convective principles and the ability to “see” the treatment. Collectively, whole mount sectioning along with the non-enhancing areas seen on MRI’s at 7-days demonstrated ablation to ALL anatomic zones and boundaries consistent with the unique ablation capabilities of convection. In Group 2, after one treatment session, 14/17 PIRADSv2 lesions ≥3 were no longer visible within the ablation zone on 7-day MRI. There were no serious adverse events intraoperatively or within one week of the treatment. CONCLUSIONS: Transurethral delivery of water vapor thermal energy can effectively ablate any zone of the prostate from apex to base, anterior to posterior, and laterally to the prostatic “capsule”. Early feasibility data using this investigational device are favorable. Source of Funding: Francis Medical, Maple Grove, MN © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1165-e1166 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Dixon More articles by this author Christopher Warlick More articles by this author Expand All Advertisement Loading ...

551 Fish Skin Compared to Cadaver Skin as a Temporary Coverage and Wound Bed Preparation for Full Thickness Burns: An Early Feasibility Trial.

Abstract Introduction Full-thickness thermal burns may require staged procedures with temporary coverage to ensure the wound bed is optimized for autografting. A potential dermal substitute for thermal injury is fish skin grafts. These are made in Iceland from freeze dried, sterilized, decellularized skin of North Atlantic cod (Gadus morhua). The gentle processing of the fish skin removes the risk of viral disease transmission to humans and retains its naturally occurring Omega3 fatty acids which are known for their pain and inflammation modulating effects. Fish skin graft has a shelf life of 3 years at room temperature, whereas cadaver skin, the current standard of care at many institutions, has to be cryopreserved, is donor derived, and contains only trace amounts of Omega3. While fish skin graft has been cleared by the FDA as a medical device for use in acute, surgical, chronic wounds, and partial thickness burns, it has not yet been indicated for use in full-thickness burns. The purpose of this clinical trial is to assess the safety and efficacy of decellularized, freeze dried fish skin as an alternative to cadaveric skin (standard of care) for temporary coverage in the setting of a full-thickness burn requiring staged grafting. Methods Patients with full thickness burns to their extremities and/or chest were randomized to have two adjacent areas (70–140 cm2 each) covered with either fish skin or cadaver skin for one week following excision. Patients then received a split thickness skin graft (STSG). Healing was observed by blinded assessors for each area weekly for three weeks, with a scarring assessment completed at 3 months post STSG. Background pain was measured by a visual analogue scale (VAS) for pain and wounds were photographed at each time point. Results Five patients are included in this initial analysis and all completed the 3-month post STSG follow up. TBSA ranged from 8–37%. The fish skin treated area was assessed to be 90% healed at the same timeframe or earlier than cadaver treated areas in all subjects. There was a trend towards a reduction in pain in the fish skin covered areas. One patient was unable to give a pain score due to heavy sedation. Adverse events were reported in all five patients, but none were associated with the use of the investigational product. Graft failures were observed in two cadaver skin covered areas and one partial failure in a fish skin covered area. Conclusions Results from this trial so far indicate that the fish skin is safe and non-inferior to cadaver skin as an early coverage for full thickness burns. Enrollment in this study is still ongoing, and patients will be followed up for 12 months.

Transcatheter mitral valve replacement: latest advances and future directions.

Mitral regurgitation remains the most common form of valve disease worldwide and given an aging population with a significant proportion of secondary mitral regurgitation, a transcatheter approach to mitral valve replacement has become a major goal of the transcatheter therapeutics field. Mitral regurgitation can be caused by disease of the leaflets (primary) or by diseases of the left atrium or left ventricle (LV) (secondary or functional), and may involve overlap of the two (mixed disease). The location of the mitral valve (and large size), the approach to anchoring a valve replacement, and concerns about left ventricular outflow tract (LVOT) obstruction are all issues that have made the transcatheter delivery of a valve replacement challenging. Despite these challenges, both transapical and transseptal devices are currently being developed, with several in early feasibility trials and several entering pivotal trials. As the field of transcatheter mitral valve replacement (TMVR) improves and develops, a critical part of evaluating patients with mitral valve disease will be utilizing the heart team approach to identify and individualize the most appropriate treatment for each patient.

The first-in-human experience with a minimally invasive, ambulatory, counterpulsation heart assist system for advanced congestive heart failure

The intravascular ventricular assist system (iVAS) is a new, minimally invasive, ambulatory counterpulsation heart assist system delivered via the subclavian artery and powered by a portable driver. It is designed for recovery, bridge to transplantation (BTT) or for prolonging medical therapy. We report the first-in-human (FIH) experience with iVAS. This is a prospective, non-randomized single arm, U.S. Food and Drug Administration (FDA)-approved early feasibility trial in patients listed for cardiac transplantation. The primary end-point was survival to transplant or stroke-free survival at 30 days. Fourteen patients were enrolled and 13 (92.8%) were treated with iVAS. At time of implant, the average age was 58 ± 6.7 years; 85% were male; 28% had ischemic cardiomyopathy; and 3 were Interagency Registry for Mechanically Assisted Devices (INTERMACS) Level 2, 9 were Level 3, and 1 was Level 4. The mean left ventricular ejection fraction was 22%, left ventricular internal diameter diastole was 7.13 mm, and 69% had moderate or severe mitral regurgitation. There were no intra-operative complications. Intensive care unit stay after implant was 6 ± 6 days. All patients were transplanted after 32 ± 21 days. There were no deaths or thromboembolic events: 1 patient required escalation of mechanical support, and post-implant complications included pleuritis/pericarditis (n = 1) and neuropathy (n = 2). No intra-operative blood transfusions were required. This study demonstrates a high rate of successful outcomes with an excellent risk-to-benefit profile. This FIH experience reveals that the iVAS can be successfully inserted in a standardized approach, provide hemodynamic support, can be interrupted for short periods, and allows for ambulation. A multicenter trial to investigate effectiveness and safety is warranted.

Interventional Therapies for Resistant Hypertension: A Brief Update

Resistant hypertension remains a clinical challenge with few management options beyond maximisation of medications. Catheter- based renal artery denervation (RDN) was proposed in 2009 as a possible therapy for resistant hypertension and early feasibility trials caused excitement among cardiologists and antihypertensive specialists, showing remarkable and sustained blood pressure reductions. In 2014, enthusiasm for RDN dampened following the SYMPLICITY 3 trial results, which showed no statistically significant difference in blood pressure between the intervention and control arms. However, hope remains for the improved management of resistant hypertension; procedural understanding, technological advancements and alternative targets - such as baroreceptor activation therapy and arteriovenous shunts - may aid the identification of those patients for whom specific interventional therapies will be effective.

Interventional Therapies for Resistant Hypertension: A Brief Update

Resistant hypertension remains a clinical challenge with few management options beyond maximisation of medications. Catheterbased renal artery denervation (RDN) was proposed in 2009 as a possible therapy for resistant hypertension and early feasibility trials caused excitement among cardiologists and antihypertensive specialists, showing remarkable and sustained blood pressure reductions. In 2014, enthusiasm for RDN dampened following the SYMPLICITY 3 trial results, which showed no statistically significant difference in blood pressure between the intervention and control arms. However, hope remains for the improved management of resistant hypertension; procedural understanding, technological advancements and alternative targets – such as baroreceptor activation therapy and arteriovenous shunts – may aid the identification of those patients for whom specific interventional therapies will be effective.

The Cadaveric Skin Biopsy Project: Description and student evaluation of an innovative approach to dermatology instruction in the preclerkship medical school curriculum

Dermatology can develop creative ways of participating in the preclerkship medical school curriculum. We sought to describe and report student survey results of a novel collaborative learning activity for medical students, directed by dermatology, histology, and gross anatomy faculty, which used cadavers to replicate the process of skin lesion biopsy and provided a realistic setting in which to learn normal-appearing and abnormal skin histology. First-year medical students were surveyed regarding the impact of this activity on their understanding of skin histology and their appreciation of dermatology and dermatologic procedures. Students were appreciative of the opportunity to perform biopsies and discover the link between the clinical presentation of a lesion and its underlying histopathology. They were less impressed with the ability of the activity to improve their understanding of the characteristics of benign versus malignant lesions. This is an early feasibility trial at 1 institution. This project represents one approach to introducing students to dermatology and dermatologic procedures and achieves institutional, Liaison Committee on Medical Education, and Association of American Medical Colleges educational goals. Overall, students highly valued the opportunities to practice clinical procedures and found it aided their understanding and appreciation of dermatology.