Primary Effectiveness Endpoint Research Articles

Differential target multiplexed spinal cord stimulation in patients with Persistent Spinal Pain Syndrome Type II: a study protocol for a 12-month multicentre cohort study (DETECT)

IntroductionDifferential target multiplexed spinal cord stimulation (DTM SCS) is a new stimulation paradigm for chronic pain management with the aim of modulating glial cells and neurons in order to rebalance...

Medical Devices Applying for Outpatient Medicare Supplemental Payments.

Medicare transitional pass-through payments (TPTPs) provide supplemental reimbursement that is intended to facilitate adoption of new devices in the outpatient setting. The US Centers for Medicare & Medicaid Services (CMS) have historically evaluated manufacturer applications for TPTPs based on newness, cost, and evidence of substantial clinical improvement, ie, the traditional pathway. In 2020, CMS introduced an alternative pathway to allow US Food and Drug Administration (FDA)-designated breakthrough devices to qualify for supplemental reimbursement without demonstrating substantial clinical improvement. To characterize CMS TPTP approval rates and the premarket evidence used by FDA to support authorization of new outpatient medical devices considered for CMS TPTP. This was a cross-sectional study of TPTP applications for new outpatient medical devices from 2017 to 2023. Using the Federal Register, CMS Outpatient Prospective Payment System final rules for fiscal years 2017 through 2023 were obtained, from which all manufacturer applications for TPTPs were identified. For each application, the CMS TPTP review pathway (traditional/alternative), CMS final decision (award/deny), and FDA authorization pathway were assessed. Characteristics of devices considered for CMS TPTPs and design, effectiveness end points, and patient demographic characteristics of premarket clinical studies used to support FDA authorization. CMS approved 17 of 43 (40%) applications for TPTPs, including all 8 (100%) alternative pathway applications for breakthrough devices and 9 of 35 applications (26%) using the traditional pathway. Devices approved for TPTPs were more likely to have been assessed in premarket clinical studies than devices denied TPTPs (12/17 [71%] vs 2/26 [8%]). Among the 14 premarket studies of TPTP-approved devices, 8 (57%) used surrogate markers as primary effectiveness end points and 5 (42%) did not meet all primary end points. The median (IQR) percentage of female, Black, and Hispanic patients among the trials that reported demographic data was 26% (17%-36%), 6% (2%-17%), and 4% (3%-5%), respectively. The findings of this cross-sectional analysis indicated that CMS more commonly awarded supplemental outpatient payment through TPTPs for devices assessed in premarket clinical studies to support FDA authorization. However, these studies often lacked generalizability to Medicare beneficiaries, used surrogate markers of effectiveness, or did not meet all primary end points. As more breakthrough devices receive FDA authorization and effectively qualify for automatic supplemental payments, strengthening premarket clinical evidence requirements for CMS TPTP approvals would provide better information to guide clinical decision-making and ensure that supplemental reimbursement enhances care for Medicare beneficiaries.

Coronary Sinus Narrowing for TreatingRefractory Angina: REDUCER-I Multicenter "Real-World" Observational Study Primary Endpoint Analysis.

Patients with refractory angina are often ineligible for revascularization and have poor quality of life despite optimal medical therapy. The coronary sinus (CS) Reducer (Shockwave Medical Inc) was safe and effective in the treatment of refractory angina in the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) randomized sham-controlled trial. This study sought to perform the primary endpoint analysis of the complete REDUCER-I (An Observational Study of the Neovasc Reducer System) study cohort. REDUCER-I is a nonrandomized, "real-world" study of patients with refractory angina treated with the CS Reducer conducted at 25 centers from 9 European countries. The primary effectiveness endpoint was an improvement in Canadian Cardiovascular Society (CCS) class at 6months. The primary safety endpoints were major adverse cardiac events and device- or procedure-related serious adverse events through 30days. Study follow-up is planned through 5 years with some interim 3-year analyses included here. From 2016 to 2023, 400 patients were enrolled, including 78.0% (312/400) male patients, 54.3% (216/398) with previous myocardial infarction, 73.6% (293/398) with previous revascularization, and 72.0% (280/389) CCS class III/IV. Major adverse cardiac event and serious adverse event rates were 1.6% (95%CI: 0.7-3.6) and 1.1% (4/371), respectively, with no deaths within 30days. At 6months, 69.8% (240/344) of patients improved by≥1 CCS class. Six-minute walk distances improved by 34.1 ± 85.8m at 6months (P< 0.0001). Interim 3-year results showed CCS class and Seattle Angina Questionnaire quality of life improvements were sustained (P< 0.0001). The complete primary endpoint analysis of the REDUCER-I study shows patients with refractoryangina were safely and effectively treated with the CS Reducer. Improvements in angina and quality of lifeappear sustained through 3 years.

Thirty-Day Outcomes from the Disrupt PAD BTK II Study of the Shockwave Intravascular Lithotripsy System for Treatment of Calcified Below-the-Knee Peripheral Arterial Disease

Below the knee (BTK) lesions may be particularly challenging to treat owing to length, diffuse disease, and extent of calcification. Landmark interventional clinical studies have not reached consensus on the optimal standard of care for BTK lesions, and many published trials excluded patients with moderate or severe lesion calcification. Calcium modification with intravascular lithotripsy (IVL) was shown to be superior to percutaneous transluminal angioplasty (PTA) in the femoropopliteal artery and successful in treating BTK lesions in pilot studies. The Disrupt BTK II study is a core-lab adjudicated, prospective, multi-center single-arm study of patients with moderate to severely calcified BTK lesions treated with the Shockwave Medical Peripheral IVL System. Disrupt BTK II enrolled 250 subjects with calcified infrapopliteal lesions and Rutherford category 3-5 presentation from 38 sites in the United States and Europe. The primary safety endpoint was major adverse limb events (MALE) or post-operative death (POD) at 30 days, a composite of all-cause death, above-ankle amputation of the index limb, and/or major reintervention of the index limb involving an infrapopliteal artery. The primary effectiveness endpoint was procedural success, defined as ≤50% residual stenosis for all treated target lesions without serious core lab-adjudicated serious angiographic complications. The study used independent angiographic and duplex ultrasound core laboratories, and follow-up is planned through two years. A total of 305 lesions in 250 patients were treated with a procedural success of 97.9%. Mean target lesion length was 76 ± 65mm, diameter stenosis was 78 ± 18%, and 84.8% had moderate or severe calcification as assessed by an independent angiographic core lab. After IVL, residual stenosis was reduced to 29%, and to 26% after optional post-dilatation and/or stent implantation. At 30 days, there were no deaths, MALE rate was 0.8%, and mean improvement in VascuQoL scores was 4.0 ± 5.0 (P<0.0001). Of the patients with baseline wounds, 15.8% healed and 53.4% were improved at 30 days. The Disrupt PAD BTK II study demonstrated that treatment with the Shockwave Medical Peripheral IVL System in patients with moderate-severe calcified lesions resulted in high procedural success, significant reduction in residual stenosis, improvements in patient QoL and wound healing, with minimal adverse events at 30-day follow-up.

BRIVA-ONE study: 12-month outcomes of brivaracetam monotherapy in clinical practice.

This study investigated the effectiveness and tolerability of brivaracetam (BRV) monotherapy in a large series of patients with epilepsy. This was a multicenter, retrospective, observational, non-interventional study in 24 hospitals across Spain. Patients aged ≥18 years who started on BRV monotherapy, either as first-line or following conversion, at least 1 year before database closure were included. Patients were evaluated at baseline and at 3, 6 and 12 months after initiation of BRV monotherapy, in accordance with usual clinical practice at these centers. Data were collected retrospectively from patients' individual charts by participating physicians. The primary effectiveness and safety endpoints were the percentage of seizure-free patients 1 year after initiation of BRV monotherapy and the proportion of patients reporting adverse events (AEs) over the complete follow-up period. Retention rates and subpopulation analysis (levetiracetam switchers, elderly and different etiologies) were also investigated. A total of 276 patients were included (48 with BRV as first-line monotherapy and 228 who converted to BRV monotherapy). The overall retention rate in monotherapy at 12 months was 89.9% (87.5% for first-line monotherapy group; 90.4% for conversion-to-monotherapy group). Seizure-freedom rates at 12 months were 77.8% (75% for first-line monotherapy group; 78.4% for conversion-to-monotherapy group). AEs occurred in 39.5% of patients at 12 months (35.4% for first-line monotherapy group; 40.4% for conversion-to-monotherapy group). Most AEs were mild-to-moderate. The most frequent AEs were irritability (12.3%) and dizziness (10.1%). The most frequent AEs leading to BRV withdrawal were dizziness (1.8%) and memory problems (1.4%). Similar outcomes in terms of effectiveness and tolerability of BRV monotherapy were observed in patients switching from levetiracetam, those with different epilepsy etiologies, and elderly patients. BRV was effective and well tolerated both as first-line monotherapy and following conversion to monotherapy in a real-world setting of patients with epilepsy. The goal of the medical treatment of epilepsy is to ensure best possible patient quality of life, by maximizing seizure control and minimizing medication toxicity. Brivaracetam (BRV) is a new-generation epilepsy treatment that is well tolerated by patients. In our study, monotherapy with BRV reduced seizures in patients who had not received other treatments and in patients who switched from a previous treatment to BRV monotherapy. BRV was well tolerated and also effective in sensitive patients (i.e., the elderly and those who had epilepsy caused by a brain tumor or a brain injury).

Safety and Effectiveness of Low-Density Lipoprotein Cholesterol-Lowering Therapy With Evolocumab for Familial Hypercholesterolemia/Hypercholesterolemia in Japan: A Real-World, Postmarketing, Single-Arm Study.

Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 approved in Japan for familial hypercholesterolemia (FH) and hypercholesterolemia; however, data on its safety and effectiveness in the real-world setting in Japan are limited. This real-world, postmarketing, single-arm study assessed the safety and effectiveness of low-density lipoprotein cholesterol lowering with evolocumab in patients with homozygous/heterozygous familial hypercholesterolemia and hypercholesterolemia with high risk in Japan (668 sites). The primary safety end point was the incidence (percentage) and number of patients with adverse drug reactions and serious adverse events during the 104-week follow-up. Primary effectiveness end points included the percentage change in low-density lipoprotein cholesterol levels from baseline to week 12, assessed using 2-sided paired t tests. The safety and effectiveness sets comprised 3724 (homozygous FH, n=108; heterozygous FH, n=2009; hypercholesterolemia with high risk, n=1607) and 2797 (homozygous FH, n=91; heterozygous FH, n=1615; hypercholesterolemia with high risk, n=1091) patients, respectively. Overall, mean age and disease duration were 63.2 and 12.3 years, respectively. Serious adverse drug reactions and serious adverse events were experienced by 0.5% and 10.3% of patients; the incidence rates of myocardial infarction and stroke were 0.7% and 0.3%, respectively. A significant mean±SD percentage change in low-density lipoprotein cholesterol levels was observed at week 12 among patients with homozygous FH (-45.7%±28.2; P<0.001), heterozygous FH (-55.9%±28.8; P<0.001), and hypercholesterolemia with high risk (-63.3%±23.7; P<0.001). Evolocumab was well tolerated, and real-world patients with familial hypercholesterolemia and hypercholesterolemia with high risk in Japan had sustained low-density lipoprotein cholesterol reduction. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02808403.

Atrial fibrillation ablation with temperature-controlled very high-power short-duration, with conventional-power, or with combined modes in clinical practice: 12-month outcomes from SECURE

Abstract Background/Introduction QDM is a contact force-sensing catheter optimized for temperature-controlled radiofrequency ablation in very high-power short-duration (vHPSD; 90 W/4 s), conventional-power (CP; ≤50 W), or vHPSD/CP combined modes. Purpose Evaluate 12-month (M) safety and effectiveness of atrial fibrillation (AF) ablations performed with 3 different ablation modes using the QDM catheter, a frequently used single tip catheter in Europe. Methods SECURE is an observational, prospective, post-market study collecting data on procedures performed per standard-of-care with up to 12M follow-up, in 16 enrolling sites in 8 countries across Europe and Israel. Index pulmonary vein (PV) isolation procedures are reported here. The primary safety endpoint is the incidence of primary adverse events (PAEs); the primary effectiveness endpoint is PV isolation (entrance block) of targeted PVs. Additional endpoints include acute reconnections, incidence of char and steam pop, 12M recurrence, repeat ablation, and healthcare utilization (HCU). Ablation strategy, impedance drop, and catheter stability were analysed with a cloud-based data management and artificial intelligence-powered algorithm. Results Since Feb 2021, 291 patients (70% male, 61±11 yrs, CHA2DS2-VASc 1.9±1.5) completed 12M follow-up in 11 sites. Most patients (175 [60.1%]) were treated for paroxysmal (PAF), 85 (29.2%) for persistent (PsAF), and 31 (10.7%) for long-standing persistent (LsPsAF) AF, under general anaesthesia (44.0%) or sedation (55.7%). A combined workflow was used in 66.0% of ablations, while vHPSD-only and CP-only were used in 13.4% and 20.6% of cases, respectively. Four (1.4%) patients reported a PAE; all resolved, and none were catheter related. Acute effectiveness was achieved in all targeted veins; 5.0% of PVs had acute reconnections, with the most common being the left superior PV. No steam pops were reported; 2 counts of char were noted in PsAF ablations with combined modes. Freedom from documented recurrence were 95.8% for PAF, 88.1% for PsAF, and 73.5% for LsPsAF (Fig 1). Freedom from repeat ablation post-blanking and freedom from cardioversion were both 96.8%. Cardiovascular hospitalization and emergency room visits decreased by 65.3% and 76.5% from 12M pre- to 12M post-procedure, respectively. Application-level analyses showed larger impedance drop and greater catheter stability with vHPSD. In procedures using a combined workflow, vHPSD was used preferentially for most PV segments, except anteriorly on the left wide area circumferential ablation (Fig 2). Conclusions Real-world data demonstrates that AF ablation with the QDM catheter is safe and effective with a low PAE rate, high 12M effectiveness, and reduced HCU. Most procedures were done with combined modes, where vHPSD was used preferentially, except at left anterior thicker regions. Larger impedance drop and greater catheter stability were observed with vHPSD applications.

Pulsed Field Ablation to Treat Paroxysmal Atrial Fibrillation: Safety and Effectiveness in the AdmIRE Pivotal Trial.

Evidence from clinical trials of early pulsed field ablation (PFA) systems in treating atrial fibrillation has demonstrated their promising potential to reduce complications associated with conventional thermal modalities while maintaining efficacy. However, the lack of a fully integrated mapping system, a staple technology of most modern electrophysiology procedures, poses limitations in lesion creation and workflow options. A novel variable-loop PFA catheter integrated with an electroanatomic mapping system has been developed that allows for real-time nonfluoroscopic procedural guidance and lesion indexing as well as feedback of tissue-to-catheter proximity. AdmIRE (Assessment of Safety and Effectiveness in Treatment Management of Atrial Fibrillation With the Bosense-Webster Irreversible Electroporation Ablation System), a multicenter, single-arm, Food and Drug Administration investigational device exemption study, evaluated the long-term safety and effectiveness of this integrated PFA system in a large United States-based drug-refractory symptomatic paroxysmal atrial fibrillation patient population. Using the PFA catheter with a compatible electroanatomic mapping system, patients with drug-refractory symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation. The primary safety end point was primary adverse event within 7 days of ablation. The primary effectiveness end point was a composite end point that included 12-month freedom from documented atrial tachyarrhythmia (ie, atrial fibrillation, atrial tachycardia, atrial flutter) episodes, failure to achieve pulmonary vein isolation, use of a nonstudy catheter for pulmonary vein isolation, repeat procedure (except for one redo during blanking), taking a new or previously failed class I or III antiarrhythmic drug at higher dose after blanking, or direct current cardioversion after blanking. At 30 centers, 277 patients with paroxysmal atrial fibrillation (61.5±10.3 years of age; 64.3% male) in the pivotal cohort underwent PFA. More than 25% of the procedures were performed without fluoroscopy. Median (Q1, Q3) pulmonary vein isolation procedure, fluoroscopy, and transpired PFA application times were 81.0 (61.0, 112.0), 7.1 (0.00, 14.3), and 31.0 (24.8, 40.9) minutes, respectively. The primary adverse event rate was 2.9% (8 of 272), with the most common complication being pericardial tamponade. The 12-month primary effectiveness end point was 74.6%. The 1-year freedom from atrial fibrillation, atrial tachycardia, or atrial flutter recurrence rate after blanking was 75.4%. Substantial improvements in quality of life were observed as early as 3 months after the procedure, concurrent with a reduction in multiple health care use measures. AdmIRE confirmed the safety and effectiveness of the variable-loop PFA catheter, with short procedure and PFA application times and low fluoroscopy exposure. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05293639.

The left atrial appendage exclusion for prophylactic stroke reduction (leaaps) trial: rationale and design

IntroductionLeft atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE. MethodsLeft Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA2DS2-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism. ConclusionThe results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF. Trial RegistrationClinicalTrials.gov, Identifier: NCT05478304, https://clinicaltrials.gov/study/NCT05478304?term=%20NCT05478304&rank=1

Effectiveness and safety of a novel crosslinked hyaluronate canalicular gel occlusive device for dry eye.

To evaluate the effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared with a commercially available hydrogel canalicular plug (Form Fit). 5 sites in the United States. Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). Adults (≥22 years) with the Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of "not applicable," patent lacrimal drainage system, and bilateral corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was noninferiority of the mean within subject change from baseline to month 3 in Schirmer score for patients receiving filler compared with plugs. The key secondary effectiveness endpoint was noninferiority of the proportion of patients with filler achieving improvement from baseline to month 3 in OSDI by a minimal clinically important difference. Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety. 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was noninferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.

A prospective, randomized, controlled, interventional clinical trial to evaluate the safety and efficacy of the medical monopoint reperfusion system for aspiration thrombectomy in acute ischemic stroke patients (SUMMIT MAX): Trial rationale and design.

Treatment of large vessel occlusion (LVO) using mechanical thrombectomy with or without intravenous thrombolysis has demonstrated better outcomes compared to medical treatment alone. Large-bore aspiration catheters have been recently introduced. Their effectiveness and safety have not been demonstrated in a randomized trial. The SUMMIT MAX study is designed to address this question. SUMMIT MAX is a randomized controlled trial where the effectiveness and safety of the large-bore Monopoint Reperfusion system (Route 92 Medical, San Mateo, CA), will be compared to the currently largest available FDA-cleared aspiration thrombectomy device the AXS Vecta Aspiration system (Stryker Neurovascular, Fremont, CA). The study is a multi-center, prospective, randomized, controlled, interventional, open label clinical trial. The hypothesis is that the effectiveness measured by the recanalization rate (modified thrombolysis in cerebrovascular infarction - mTICI) and safety measured by symptomatic intracranial hemorrhage rate (sICH) of the medical monopoint reperfusion system is non-inferior to the AXS Vecta Aspiration system. Up to 250 subjects are enrolled with at least 50% of subjects enrolled by US sites. The primary effectiveness endpoint is successful arterial revascularization defined as an mTICI score ≥ 2b after use of the assigned device adjudicated by an independent core lab. The primary safety endpoint is defined as sICH within 24 h (-8/+24) post-procedure. Secondary endpoints include successful arterial revascularization defined as a mTICI score ≥ 2b after use of the assigned device with or without adjunctive therapy; device-related serious adverse events; all asymptomatic hemorrhages; time from groin puncture to final angiogram; and rate of first pass effect defined as mTICI 2b after first pass with the assigned device stratified by age (≤85, ≥ 86). SUMMIT MAX is a randomized controlled trial comparing the effectiveness and safety of a new large bore class of aspiration devices to the currently largest FDA-cleared aspiration device available.

Effective and durable repigmentation for stable vitiligo: A randomized within-subject controlled trial assessing treatment with autologous skin cell suspension transplantation

BackgroundVitiligo lesions are often challenging to repigment with conventional medical therapies. Surgical autologous melanocyte transfer methods can be utilized for stable vitiligo but demand specialized skills and equipment. A point-of-care autologous cell harvesting device was designed enabling simple preparation of autologous skin cell suspension (ASCS) containing melanocytes, keratinocytes, and fibroblasts providing a straightforward approach for cellular transplantation. ObjectiveTo evaluate the safety and effectiveness of ASCS for repigmentation of stable vitiligo lesions among adults. MethodsA US multicenter, randomized, within-subject controlled trial compared ASCS to NB-UVB only (Control) in similar vitiligo lesions. ASCS was applied after laser skin resurfacing and followed by NB-UVB treatment. The primary effectiveness endpoint was the proportion of lesions achieving ≥80% repigmentation at week-24. Repigmentation durability was assessed at week-52. ResultsAmong 25 subjects, 36% of ASCS-treated lesions achieved ≥80% repigmentation at week-24 compared to 0% for Control (p<0.025), with durability through week-52. The safety profile of ASCS was acceptable, with favorable patient- and investigator-reported outcomes. LimitationsStudy sample size limited robust subgroup analyses. ConclusionApplication of ASCS is a safe and effective treatment for repigmentation of stable vitiligo lesions with the potential to improve health-related quality of life and reduce burden of disease.

Safety and Feasibility of an Implanted Inferior Vena Cava Sensor for Accurate Volume Assessment: FUTURE-HF2 Trial.

A novel implantable sensor has been designed to accurately measure inferior vena cava (IVC) area to allow daily monitoring of IVC area and collapse to predict congestion in heart failure (HF). A prospective, multicenter, single arm, Early Feasibility Study enrolled 15 HF patients (irrespective of ejection fraction) with a HF event in the previous 12 months, an elevated NT-proBNP, and receiving ≥40 mg of furosemide equivalent. Primary endpoints included successful deployment without procedure-related (30 days) or sensor-related complications (three months) and successful data transmission to a secure database (3 months). Accuracy of sensor-derived IVC area, patient adherence, NYHA classification, and KCCQ were assessed from baseline to three months. Patient-specific signal alterations were correlated with clinical presentation to guide interventions. Fifteen patients underwent implantation (66±12 years; 47% female; 27% HFpEF, NT-ProBNP 2569 (median, IQR: (1674-5187)) ng/L; 87% NYHA Class III). All patients met the primary safety and effectiveness endpoints. Sensor-derived IVC area showed excellent agreement with concurrent CT (R2=0.99, mean absolute error=11.15 mm2). Median adherence to daily readings was 98% (IQR: 86-100%) per patient-month. A significant improvement was seen in NYHA class and a non-significant improvement was observed for KCCQ. Implantation of a novel IVC sensor (FIRE1) was feasible, uncomplicated, and safe. Sensor outputs aligned with clinical presentation and improvements in clinical outcomes. Future investigation to establish the IVC sensor remote management of HF is strongly warranted.

Early results from the pivotal trial substudy of the GORE EXCLUDER conformable endoprosthesis in angulated necks

ObjectiveTo report the investigational device exemption study 1-year clinical outcomes of the high neck angulation (HNA) substudy of the GORE EXCLUDER Conformable AAA Endoprosthesis (EXCC) for treatment of infrarenal abdominal aortic aneurysms (AAAs). MethodsThis study is a prospective, multicenter clinical trial conducted in the United States and included core laboratory assessment of imaging and independent event adjudication. Anatomical criteria for enrollment in the HNA substudy included infrarenal aortic neck angulation >60° and ≤90° with aortic neck length ≥10 mm. Primary safety end points included estimated blood loss of >1000 mL, death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure, and thromboembolic events. Primary effectiveness end points included technical success, absence from type I and III endoleaks, migration (≥10 mm), sac enlargement (≥5 mm), sac rupture, and conversion to open repair. ResultsBetween January 2018 and February 2022, 95 patients were enrolled in the HNA substudy across 35 sites. Of the 95 patients, 71 (74.7%) were male and the cohort average age was 74.4 years. The mean infrarenal proximal aortic neck angle was 71.6° and the mean AAA size was 62.9 mm. Overall technical success was achieved in 93 patients (97.9%). Freedom from a primary safety end point through 30 days was 96.7%; 3 (3.3%) patients had an estimated blood loss of >1000 mL. Freedom from the primary effectiveness at 12 months was achieved in 94.8%. Four patients (4.3%) had a type IA endoleak; intervention after the procedure was not required and no subsequent interventions or sac enlargement were noted in these patients. At 12 months, 29 patients (39.7%) experienced a type II endoleak and 1 (1.3%) patient experienced AAA sac expansion of ≥5 mm. Through 12 months, 1 patient (1.3%) had a conversion to open surgical repair. There were no aneurysm-related deaths, ruptures, or migration through 12 months. ConclusionsThe investigational device exemption study demonstrates safety and effectiveness of the GORE EXCLUDER Conformable AAA Endoprosthesis device in AAA with highly angulated necks (>60° and ≤90°) are preserved at the 12-month follow-up.

Lip Augmentation With Saypha LIPS Lidocaine: A Postmarket, Prospective, Open-Label, Randomized Clinical Study To Evaluate Its Efficacy and Short- and Long-term Safety.

Versatility, biocompatibility, and reversibility make hyaluronic acid fillers the backbone of minimally invasive lip augmentation procedures. The aim of this study was to assess the effectiveness and short- and long-term safety of Saypha LIPS Lidocaine (Croma Pharma, Leobendorf, Austria) for lip augmentation to correct moderate to severe lip volume deficiency (grade 1-3 lip fullness score [LFS]). In this postmarket, prospective, open-label, multicenter, randomized clinical study, 114 patients were initially treated (with optional touch-up treatment at Week 3). Retrograde and bolus techniques were employed with defined needles or cannula. The primary effectiveness endpoint was the proportion of patients with lip volume improvement of LFS ≥ 1 grade vs baseline at Week 6 (ie, responders); with follow-up (FU) for secondary effectiveness at Months 6, 12, and 18. Evaluation scores included the LFS, Global Aesthetic Improvement Scale (investigator and patient), patient satisfaction questionnaire FACE-Q, and a numerical pain rating scale. At Week 6, >90% of the patients were responders (lower-lip: 95% CI, 92.24-99.43, P = .0071; upper-lip: 95% CI, 90.95-99.00, P = .0234), with post hoc analyses showing the outcome was influenced by the initial volume deficiency and total volume injected, but not by touch-up treatment. At Month 6, 90% of the patients were responders; at Month 12, 70%; and at Month 18, >40% still had a visible effect. Adverse events were mostly procedural, mild, and temporary. Pain perception was significantly reduced 15 minutes after the procedure. Aesthetic improvement and patient satisfaction were rated as high at all time points. Saypha LIPS Lidocaine for lip augmentation showed long-term aesthetic improvement and safety.

Impact of aspirin dose according to race in secondary prevention of atherosclerotic cardiovascular disease: a secondary analysis of the ADAPTABLE randomised controlled trial

ObjectivesTo evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD).DesignA...

One-year outcomes of a novel venous stent for symptomatic iliofemoral venous obstruction: prospective cohort study

BackgroundA stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction.MethodsEligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures.ResultsBetween December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93–95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (− 4.30 ± 3.66) and 12 months (− 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001).ConclusionsThe 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.

Effect of an Intrapartum Pelvic Dilator Device on Levator Ani Muscle Avulsion During Primiparous Vaginal Delivery: A Pilot Randomized Controlled Trial

Introduction and HypothesisThe objective was to evaluate the safety and effectiveness of an intrapartum electromechanical pelvic floor dilator designed to reduce the risk of levator ani muscle (LAM) avulsion during vaginal delivery.MethodsA multicenter, randomized controlled trial enrolled nulliparous participants planning vaginal delivery. During the first stage of labor, participants were randomized to receive the intravaginal device or standard-of-care labor management. The primary effectiveness endpoint was the presence of full LAM avulsion on transperineal pelvic-floor ultrasound at 3 months. Three urogynecologists performed blinded interpretation of ultrasound images. The primary safety endpoint was adverse events (AEs) through 3 months.ResultsA total of 214 women were randomized to Device (n = 113) or Control (n = 101) arms. Of 113 Device assignees, 82 had a device placed, of whom 68 delivered vaginally. Of 101 Control participants, 85 delivered vaginally. At 3 months, 110 participants, 46 Device subjects who received full device treatment, and 64 Controls underwent ultrasound for the per-protocol analysis. No full LAM avulsions (0.0%) occurred in the Device group versus 7 out of 64 (10.9%) in the Control group (p = 0.040; two-tailed Fisher’s test). A single maternal serious AE (laceration) was device related; no neonate serious AEs were device related.ConclusionsThe pelvic floor dilator device significantly reduced the incidence of complete LAM avulsion in nulliparous individuals undergoing first vaginal childbirth. The dilator demonstrated an acceptable safety profile and was well received by recipients. Use of the intrapartum electromechanical pelvic floor dilator in laboring nulliparous individuals may reduce the rate of LAM avulsion, an injury associated with serious sequelae including pelvic organ prolapse.

Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial

BackgroundMonitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. ObjectivesThe purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. MethodsFollowing GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. ResultsBetween February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. ConclusionsRemote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure–guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059)

Intracardiac vs transesophageal echocardiography for left atrial appendage occlusion: An updated systematic review and meta-analysis

BackgroundMultiple studies continue to evaluate the use of intracardiac echocardiography (ICE) and transesophageal echocardiography (TEE) for guiding left atrial appendage occlusion (LAAO). ObjectiveThe purpose of this study was to conduct an updated meta-analysis comparing the effectiveness and safety outcomes of both imaging modalities. MethodsPubMed, Cochrane, and Embase were searched for studies comparing ICE vs TEE to guide LAAO. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. The primary effectiveness endpoint was procedural success. The primary safety endpoint included the overall complications rate. Additional safety outcomes were assessed as secondary endpoints. Subgroup analysis of primary endpoints was conducted according to device type (Amulet, LAmbre, Watchman, Watchman FLX) and study region (American, Asia, Europe). R Version 4.3.1 was used for all statistical analyses. ResultsOur meta-analysis included 19 observational studies encompassing 42,474 patients, of whom 4415 (10.4%) underwent ICE-guided LAAO. Compared with TEE, ICE was associated with a marginally higher procedural success (OR 1.33; 95% CI 1.01–1.76; P = .04; I2 = 0%). There was no significant difference in the overall complications rate (OR 1.02; 95% CI 0.77–1.36; P = .89; I2 = 5%). However, ICE showed higher rates of pericardial effusion (OR 2.11; 95% CI 1.47–3.03; P <.001; I2 = 0%) and residual iatrogenic atrial septal defect (iASD) (OR 1.52; 95% CI 1.15–2.03; P <.004; I2 = 0%). Subgroup analysis revealed variations in procedural success within the ICE group across study regions (P = .02). ConclusionIn this updated meta-analysis, the increasing adoption of ICE-guided LAAO demonstrated higher procedural success rates compared to TEE, although with limited statistical significance. Overall complication rates were similar; however, ICE showed higher rates of pericardial effusion and residual iASD.