Primary Effectiveness Endpoint Research Articles

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.

Retrospective, Real Life Study on the Effectiveness and Safety of a Depigmented-Polymerized Subcutaneous Vaccine Containing a Mixture of Grasses and Olea europaea

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients’ symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments.

Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses. To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial. The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024. Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD. The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion. A total of 15 076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10 352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence. In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events. ClinicalTrials.gov Identifier: NCT02697916.

Effectiveness of degradable polymer film in the management of severe or moderate intrauterine adhesions (PREG-2): a randomized, double-blind, multicenter, stratified, superiority trial

To study the effectiveness of a new intrauterine degradable polymer film (Womed Leaf®) in the management of moderate to severe IUA. PREG2 study was a multi-centre, double-blind, randomised, controlled, stratified, two-arm superiority clinical trial conducted in 16 centres in 7 countries. Patients ≥18 years scheduled for hysteroscopic adhesiolysis because of symptomatic severe or moderate adhesions (according to American fertility society (AFS) IUA score) were considered eligible for the study. Following adhesiolysis, patients were randomised at a 1:1 ratio to either have a Womed Leaf film inserted (intervention group) or not (control group). The primary effectiveness endpoint of the study was the change in AFS IUA score on second-look hysteroscopy (SLH), assessed by an independent evaluator, compared to baseline. Information on rate of no IUA and responder rate were collected as secondary effectiveness outcomes, and reported adverse events and patient reported outcomes as safety and tolerability measures. Between October 26, 2021, and September 28, 2023, a total of 160 women were randomised (Womed Leaf: n=75 and controls: n=85). The reduction in IUA AFS score on SLH was significantly higher in the intervention compared to the control group (mean 5.2 ± 2.8 vs. 4.2 ± 3.2; p=0.0153). Similarly, the absence of adhesions on SLH was significantly higher in the intervention group (41% vs 24% OR 2.44 [CI 1.161 - 5.116]; p=0.0189). None of the reported adverse events were serious or considered related to the device. Womed Leaf is effective and safe in the management of symptomatic severe or moderate intrauterine adhesions.

Long-Term Results of Physician-Modified Endografts for the Treatment of Elective, Symptomatic, and Ruptured Juxtarenal Abdominal Aortic Aneurysms.

The objective of this study was to report long-term results of an ongoing physician-sponsored, investigational device exemption (IDE) pivotal clinical trial using physician-modified endovascular grafts (PMEGs) for the treatment of patients with juxtarenal aortic aneurysms. Data from a nonrandomized, prospective, consecutively enrolling IDE clinical trial were used. Data collection began on April 1, 2011, and data lock occurred on January 2, 2024, with outcomes analysis through December 31, 2023. Primary safety and effectiveness end points were used to measure treatment success. The safety end point was defined as the proportion of subjects who experienced a major adverse event within 30 days of the procedure. The effectiveness end point was the proportion of subjects who achieved treatment success. Treatment success required the following at 12 months: technical success, defined as successful delivery and deployment of a PMEG with preservation of intended branch vessels; and freedom from: type I and III endoleak, stent graft migration >10mm, aortic aneurysm sack enlargement >5mm, and aortic aneurysm rupture or open conversion. Over the 12-year study period, 228 patients were enrolled; 205 began the implant procedure, and 203 received PMEG. Thirteen patients withdrew prior to PMEG. Two withdrew (<1.0%) after failure to deploy due to tortuous iliac anatomy and are tracked as intent to treat, and a total of 24 withdrew after receiving the PMEG implant. Forty-four patients died during the study period. A total of 14 were deemed lost to follow-up. Fifty-nine completed the 5-year follow-up period, and 62 remain active in follow-up visits.Aneurysm anatomy, operative details, and lengths of stay were recorded and included: aneurysm diameter (mean, 67.5mm; range, 49-124mm), proximal seal zone length (mean, 41.6mm; range, 18.9-92.9mm), graft modification time (mean, 48.7min), procedure time (mean, 137.7min), fluoroscopy time (mean, 33.8min), contrast material use (mean, 93.0mL), estimated blood loss (mean, 118.8mL), length of hospital stay (mean, 3.7d), and intensive care unit length of stay (mean, 1.6d).A total of 575 fenestrations were created for 387 renal arteries, 181 superior mesenteric arteries (SMAs), and 7 celiac arteries. Renal arteries were in 96% of patients and included 410 renal artery stents in 203 patients. The SMA was stented as needed and included one patient with an SMA stent placed before the procedure, 19 during the procedure, and 2 patients who underwent stent placement after the procedure. There were no open conversions or device migrations and 1 partial explant due to late distal graft occlusion. Three ruptures (1.4%) were recorded on days 830, 1346, and 1460. There was 1 presumed graft infection at 750 days (<0.5%) treated with? Thirty-day all-cause mortality was 2.9% (6/204). One type Ia, 1 type Ib, and 7 type III endoleaks were identified during follow-up and treated with successful reintervention at the 1-year period. The overall rate of major adverse events at 30 days was 15% (29/194). Technical success was 93.7%, and overall treatment success was 82.6%. PMEG can be performed with low rates of long-term morbidity and mortality, confirming our early and midterm reports that endovascular repair with PMEG is safe, durable, and effective for managing patients with juxtarenal aortic aneurysms. While historically considered experimental, these results suggest that PMEG is a safe and durable option and should be considered for patients where off-the-shelf devices are not available.