P1053Higher density mapping efficiency and ease of maneuverability of a novel mapping catheter in complex arrhythmias

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Sarkozy ◽  
J V Vijgen ◽  
T D De Potter ◽  
R S Schilling ◽  
V M Markides
Keyword(s):  
Left Ventricle ◽  
Primary Endpoint ◽  
Ease Of Use ◽  
Serious Adverse Events ◽  
Density Mapping ◽  
Post Procedure ◽  
Fast Activation ◽  
Multi Center Study ◽  
Met Expectations ◽  
Mapping Catheter

Abstract Background An advanced mapping catheter has been developed to facilitate reliable identification of ablation targets in complex arrythmias. This catheter has 48 platinum-iridium mapping electrodes, with 6 of those electrodes distributed across each of the 8 spines (Figure).  Purpose To assess the mapping efficiency of the catheter in a feasibility study and characterize the ease of use through physician feedback. Methods This prospective, single arm, non-randomized, multi-center study was conducted at 5 European sites. The primary endpoint was the completion of protocol required fast activation and electro anatomical pre-ablation mapping. Catheter performance regarding its deployment, ease of use, and mapping results was assessed via a post procedure physician feedback survey. Physician feedback rated as ≥4 on the 7-point Likert scale (1 = poor, 7= excellent) indicated that the catheter met expectations. Subjects were followed 7 days post procedure for serious adverse events (SAEs). Results Thirty-one patients (age: 67.8 ± 8.52 years, 87.1% men) were enrolled (11 ventricular tachycardia [VT], 10 scar-related AT/re-do paroxysmal AF [PAF], 10 persistent AF[PsAF]). 28 subjects had study catheter inserted for mapping purposes. The primary endpoint was achieved in 23/28 patients (82.1%). Five patients did not complete pre-ablation mapping requirements due to physicians’ choice as voltage mapping was considered sufficient (N = 3), inability of catheter to reach the basal inferior septal left ventricle (N = 1), and physician’s decision to perform pulmonary vein isolation prior to protocol-required mapping (N = 1). Pre-ablation median mapping times (Q1/Q3) were 121.0 (71.0, 146.0), 72.5 (51.0, 107.0), and 31.5 (13.5, 48.0) minutes for the VT, AT/PAF, and PsAF groups, respectively. Median total procedure times for VT, AT/PAF, and PsAF were 192, 193 and 146 minutes, respectively. Median points acquired per minute were 24.4, 43.6, and 69.8 for the VT, AT/PAF, and PsAF subgroups. All subjects (16/16, 100%) who had conduction channel(s), gaps(s), or critical isthmus identified had the areas appropriately mapped. The incidence of SAEs observed was low (1/30; 3.3%) with only 1 heart failure case reported.  Operators rated the ability to deploy as met expectations or better (median score: 5.0, Q1/Q3 4.0,6.0). Ability to maneuver was rated very positively in the atria: the catheter met expectations or was at least comparable to other devices for 90.0% of LA and 100.0% of right atrium (RA) use. Users felt the catheter met expectations or better in its ability to reach the atria and ventricles; 85%, 100%, and 60% of users ranked the catheter with a score of ≥ 4 in the LA, RA, and left ventricle, respectively. Conclusion(s): Our results demonstrate the feasibility of the high-density mapping catheter to efficiently map complex arrythmias with a good safety profile. Post procedural operators’ feedback indicates satisfaction with the ease of use and maneuverability. Abstract Figure

scholarly journals P1404A PHASE 2 OPEN-LABEL, SINGLE-ARM, FIRST JAPANESE STUDY OF TENAPANOR, A NOVEL PHOSPHATE ABSORPTION INHIBITOR, FOCUSING ON PILL BURDEN DECREASE IN PATIENTS WITH HYPERPHOSPHATEMIA UNDERGOING HEMODIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tadao Akizawa ◽  
Hironori Kanda ◽  
Masayuki Takanuma ◽  
Jun Kinoshita ◽  
Masafumi Fukagawa
Keyword(s):  
Primary Endpoint ◽  
Serum Phosphorus ◽  
Phosphate Binders ◽  
Pill Burden ◽  
Phosphorus Level ◽  
Serum Phosphorus Level ◽  
Open Label ◽  
Serious Adverse Events ◽  
Phosphate Absorption ◽  
Phosphorus Control

Abstract Background and Aims Phosphate binders (PB) are usually prescribed to dialysis patients with hyperphosphatemia. Several studies have reported that higher PB pill burden may reduce adherence and lead to insufficient phosphorus control. Tenapanor is an investigational, minimally absorbed, orally administered, non-binder, small-molecule that inhibits the sodium/hydrogen exchanger isoform 3 (NHE3) in development for the control of serum phosphorus. A previous Ph3 study sponsored by Ardelyx, Inc. (NCT02675998) showed a significant phosphorus decrease compared to the placebo in patients with hyperphosphatemia undergoing hemodialysis (HD) in the US. Tenapanor was expected to reduce PB pill burden since it is administered as one small pill, taken twice a day. This was the first study in Japanese HD patients, which aimed to confirm whether tenapanor reduces the pill burden of PB. Method This was a multicenter, open-label, single-arm Ph2 study. The study consists of a screening period, a 3-week observation period, and a 26-week treatment period. Patients whose serum phosphorus level was ≥ 3.5 and ≤ 7.0 mg/dL, taking at least two PB pills three times a day were enrolled. The patients started to receive 30 mg of tenapanor twice daily. The tenapanor dose could be reduced in a step-wise manner (60, 40, 20 and 10 mg/day) at the investigator’s discretion, based on GI tolerability. PB treatment was continued according to individual regimens, however, the dose could be adjusted appropriately to maintain serum phosphorus level within ±0.5 mg/dL from the baseline. The primary endpoint was an achievement of at least a 30% decrease in the mean of the total number of PB and tenapanor pills compared to the number of PB pills at baseline. The proportion of patients who achieved at least a 30 % decrease were tested using binomial test with a threshold level of 20% and a one-sided significance level of 0.025. The analysis was conducted using the data as of Dec25, 2019. Results The primary endpoint was met. Of 67 enrolled patients at the timing of analysis, 48 patients (71.6%, [95% CI: 59.3% - 82.0%], p<0.001) achieved a 30% decrease in the total number of PB and tenapanor pills, and of those, 35 patients (52.2%, [95% CI: 39.7% - 64.6%]) achieved a 50% decrease and 18 patients (26.9%) no longer required the use of any PB at week 26. Mean phosphorus levels were maintained during the study from 5.2 mg/dL at the baseline to 4.7 mg/dL at week 26. The most frequent adverse event was diarrhea (76.1%), which was mostly mild to moderate. Only four patients discontinued the study due to diarrhea. Serious adverse events were reported in five patients, only two of which were related to tenapanor (diarrhea and acute myocardial infarction). Conclusion Tenapanor was able to provide phosphorus control with significantly fewer pills compared to PB. AE profile was similar to previous US studies. This result suggests that tenapanor, a non-binder, phosphate absorption inhibitor that provides a novel approach to the management of hyperphosphatemia, could potentially improve drug adherence by reducing PB pill burden while maintaining effective phosphorus control.

Enhanced pathologic tumor response with two cycles of neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6008-6008
Author(s):  
Ravindra Uppaluri ◽  
Rebecca Chernock ◽  
Mena Mansour ◽  
Ryan Jackson ◽  
Jason Rich ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Tumor Response ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Fold Increase ◽  
Pathologic Response ◽  
Smoking History ◽  
Blood Collection ◽  
Serious Adverse Events ◽  
Phase 2 Trial

6008 Background: We reported that one cycle of neoadjuvant pembrolizumab induced pathologic tumor response in >10% (pTR-any) and in >50% (pTR-2) of the resection bed in 44% and 22% of patients (pts) with surgically resectable HPV-negative, Stage III/IV HNSCC ( Clin Cancer Res 2020). We hypothesized that two cycles of neoadjuvant pembrolizumab would induce pTR-2 in 50% of pts. Increasing the pathologic response rate may favorably impact clinical outcomes. Methods: Multi-institutional phase 2 trial where pts with locally advanced, HPV-negative HNSCC received two cycles of pembrolizumab (200 mg), given 42 and 21 days prior to surgery. Resected tumor was analyzed by two independent pathologists for pTR (tumor necrosis and/or giant cell/histiocytic reaction to keratinous debris) in the resection bed (primary tumor and/or lymph nodes). Additional definitions: pTR-1 (>10-49%) and major pathologic response ( > 90%). The primary endpoint was pTR-2. A sample size of 26 pts was needed to detect a significantly higher pTR-2 rate of 50%, with 80% power using a one-sided alpha level of 0.05. Pts were followed for serious adverse events (AEs) for 30 days after surgery and for AEs of clinical interest for 90 days following the last dose of pembrolizumab. Pts underwent baseline blood collection and tumor biopsies to match with blood and surgical specimens obtained post-pembrolizumab. Planned correlatives included PD-L1 expression, immune function, and molecular signatures of activation in the pre- and post-treatment blood and tumor tissue. Results: Characteristics of 29 enrolled and treated pts were median age 62 (30-82) yrs, smoking history 62% (18 pts); clinical stage T2 (n = 6), T3 (n = 5), T4 (n = 18) and N0/1 (n = 17), N2 (n = 12). All treated patients received two cycles of neoadjuvant pembrolizumab, which was tolerated well with only one (3%) grade 3 AE (rash) and no grade 4 AEs. The primary endpoint was evaluable in 25 pts, and not evaluable in 4 pts (one pt withdrew before surgery and in three pts, pTR review was pending). pTR-2 occurred in 44% (11 of 25 pts), and 4 (16%) of these pts had a major pathologic response including 1 (4%) pathologic CR at the primary site. Conclusions: Two (vs one) cycles of neoadjuvant pembrolizumab resulted in a two-fold increase in the frequency of pTR-2 (44% vs 22%). These data imply that the frequency of pTR to neoadjuvant pembrolizumab can be improved by increasing the number of cycles and the treatment interval. Clinical trial information: NCT02296684.

Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial

2021 ◽  
pp. bjophthalmol-2021-319067
Author(s):  
Felix Friedrich Reichel ◽  
Stylianos Michalakis ◽  
Barbara Wilhelm ◽  
Ditta Zobor ◽  
Regine Muehlfriedel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Primary Endpoint ◽  
Statistical Power ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Small Sample ◽  
Functional Improvement ◽  
Limiting Factor ◽  
Serious Adverse Events

AimsTo determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582).MethodsDetails of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy.ResultsNo adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye.ConclusionThe results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

Phase I/II trial of pembrolizumab and cabozantinib in the treatment of metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4544-4544
Author(s):  
Elizabeth R Kessler ◽  
Junxiao Hu ◽  
Geetika Srivastava ◽  
Douglas Jerome Kemme ◽  
Praveena Iruku ◽  
...  
Keyword(s):  
Phase I ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Controlled Trial ◽  
Objective Response ◽  
Risk Category ◽  
Serious Adverse Events ◽  
Line Therapy

4544 Background: Checkpoint inhibitors (CPI) and vascular endothelial growth factor receptor inhibitors (VEGFi) are standard treatments for patients (pts) with mRCC. This phase I/II study evaluated the safety and efficacy of the novel combination of pembrolizumab (pembro) and cabozantinib (cabo). The phase I dose escalation data was presented at ASCO GU 2019. We now report the objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicity of patients in the phase II dose expansion. Methods: Eligible pts had metastatic clear cell (ccRCC) or non-clear cell (nccRCC) histology, normal organ function, ECOG 0-1, and no prior exposure to pembro or cabo. Pts could be treatment-naïve or have received prior CPI and/or VEGFi. Pts were dosed at the recommended phase 2 dose of pembro 200 mg IV Q3W in combination with cabo 60 mg PO QD. Scans were obtained every 9 weeks. Treatment beyond progression, in the setting of continued clinical benefit, was allowed. The primary endpoint was ORR. Simon’s two-stage design was implemented to test the null hypothesis that ORR ≤ 0.20 versus the alternative that ORR ≥ 0.50. Results: Forty pts were enrolled, of which 34 pts (85%) had ccRCC and 6 pts (15%) had nccRCC. This was first-line treatment for 15 pts (38%) and second- and subsequent-line therapy for 25 pts (62%). IDMC risk category was favorable in 15%, intermediate in 72.5%, and poor in 12.5% of pts. Prior therapies included VEGFi in 17 pts (43%), CPI in 17 pts (43%), and 9 pts (23%) had both prior VEGFi and CPI in combination or sequentially. At a median follow up of 17.8 months (mo), the ORR was 60% (95% CI 0.458-1.00), clinical benefit rate (CBR) was 92.5% (95% CI 0.817-1.00), median time to response was 4.2 mo; median duration of response was 8.4 mo. Three of six nccRCC pts achieved partial response. Median PFS was 10.4 mo (95% CI 6.3 mo-NR). Median OS was not reached. Twelve patients remain on treatment. The most common grade 1 and 2 (G1/2) treatment-related AEs were diarrhea (53%), fatigue (49%), weight loss (47%), nausea (43%), and dysgeusia (43%). Twenty-five patients (47%) experienced a treatment-related G3 AE and there were no G4 related AEs. Thirteen pts experienced serious adverse events, 8 of which were related to treatment: G3 transaminitis and hypoglycemia were attributed to the combination; G3 pancreatitis, nephritis, and pneumonitis attributed to pembro; G3 pulmonary embolus, confusion due to reversible posterior leukoencephalopathy (RPLS), and stroke attributed to cabo. There was one treatment-related death in the pt with RPLS, possibly related to cabo. Conclusions: This study of the combination of pembrolizumab 200mg and cabozantinib 60mg met the primary endpoint of ORR. Benefit was seen in first- and subsequent-line therapy. The safety profile was manageable. This combination warrants further confirmation in a randomized controlled trial. Clinical trial information: NCT03149822.

scholarly journals Enhanced ventricular tachycardia substrate resolution with a novel omnipolar high-density mapping catheter: the omnimapping study

2019 ◽  
Vol 58 (3) ◽  
pp. 355-362 ◽  
Author(s):  
Riccardo Proietti ◽  
Ahmed M. Adlan ◽  
Rory Dowd ◽  
Shershah Assadullah ◽  
Bashar Aldhoon ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
High Density ◽  
Density Mapping ◽  
Mapping Catheter

scholarly journals Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

2019 ◽  
Vol 78 (6) ◽  
pp. 754-760 ◽  
Author(s):  
Sudha Visvanathan ◽  
Stefan Daniluk ◽  
Rafał Ptaszyński ◽  
Ulf Müller-Ladner ◽  
Meera Ramanujam ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Primary Endpoint ◽  
Study Drug ◽  
Nuclear Factor Κb ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Autoantibody Production ◽  
Bone Resorption Markers

ObjectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).MethodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.ResultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40–CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.ConclusionAlthough blockade of the CD40–CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.Trial registration numberNCT01751776

Relation between patient satisfaction, compliance and the clinical benefit of a teletreatment application for chronic pain

2010 ◽  
Vol 16 (6) ◽  
pp. 322-328 ◽  
Author(s):  
Rianne MHA Huis in 't Veld ◽  
Stephanie M Kosterink ◽  
Tom Barbe ◽  
Agneta Lindegård ◽  
Tobias Marecek ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Patient Satisfaction ◽  
Clinical Benefit ◽  
Ease Of Use ◽  
Activity Data ◽  
Pain Disability ◽  
Key Indicator ◽  
Neck And Shoulder Pain ◽  
Actual Use ◽  
Met Expectations

We investigated the ease of use and usefulness as a measure of patient satisfaction, compliance, clinical benefit and its mutual relationships concerning a teletreatment application for chronic pain. Fifty-two subjects with neck and shoulder pain received and completed a four-week myofeedback-based teletreatment intervention. Prior to the onset of the intervention (at baseline) and immediately after the intervention they were asked to fill in questionnaires to measure discrepancies (gap scores) between expectations and experiences with the ease of use and usefulness of the treatment, as well as pain intensity and pain disability. In addition, the actual use of the system (i.e. the volume of muscle activity data available on the server) was logged. The subjects reported a significantly higher score on ease of use after the intervention compared to baseline, suggesting that the equipment was easier to use than they expected. Compliance was associated with clinical benefit. There was no significant relation between patient satisfaction and compliance. Patient satisfaction is a key indicator of how well the telemedicine treatment met expectations and compliance is important because of its association with clinical outcomes.

scholarly journals ADAPT technique with ACE68 and ACE64 reperfusion catheters in ischemic stroke treatment: results from the PROMISE study

2018 ◽  
Vol 11 (3) ◽  
pp. 226-231 ◽  
Author(s):  
Peter Schramm ◽  
Pedro Navia ◽  
Rosario Papa ◽  
Joaquin Zamarro ◽  
Alejandro Tomasello ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Randomized Trials ◽  
Similar Efficacy ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Serious Adverse Events ◽  
Clinical Trial Registration ◽  
Aspiration Thrombectomy ◽  
Stroke Treatment ◽  
Post Procedure

Background and purposeThe recent randomized trials demonstrated the benefit of mechanical thrombectomy in stroke therapy. However, treatment using different strategies is an ongoing area of investigation. The PROMISE study analyzed the safety and effectiveness of the Penumbra System with the ACE68 and ACE64 reperfusion catheters in aspiration thrombectomy of stroke, using A Direct Aspiration First Pass Technique (ADAPT).MethodsPROMISE was a prospective study which enrolled 204 patients with intracranial anterior circulation large vessel occlusion (LVO) ischemic stroke in 20 centers from February 2016 to May 2017. Initial treatment was with the ACE68/ACE64 catheters within 6 hours of symptom onset. Imaging and safety review was performed by an independent Core Laboratory and a Clinical Events Committee. The primary angiographic outcome was revascularization to mTICI 2b-3 at immediate post-procedure and the primary clinical outcome was 90-day modified Rankin Scale (mRS) score ≤2. Safety assessment included device- and procedure-related serious adverse events (SAEs), symptomatic intracranial hemorrhage (sICH), mortality, and embolization of new territory (ENT).ResultsEnrolled patients had a median age of 74 (IQR 65–80) years and a median admission NIHSS of 16 (IQR 11–20). The post-procedure mTICI 2b-3 revascularization rate was 93.1% and the 90-day mRS 0–2 rate was 61%. Device- and procedure-related SAEs at 24 hours occurred in 1.5% and 3.4%, respectively, 90-day mortality was 7.5%, sICH occurred in 2.9% while ENT occurred in 1.5%.ConclusionsFor frontline therapy of LVO stroke, the ACE68/ACE64 catheters for aspiration thrombectomy were found to be safe and showed similar efficacy to randomized trials using other revascularization techniques.Clinical Trial RegistrationNCT02678169; Pre-results.

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