Egna, Italy
ConTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing
Cardiac pacing with implantable electronic cardiac devices and transvenous leads has been introduced since 1960 and is considered a safe, effective and low-risk therapy. The most common indications for permanent cardiac pacing are sinus node dysfunction and atrioventricular blocks. In Europe, pacemaker implants exceed 1000 per million inhabitants. The aim of this therapy is not only to improve patients survival but also their quality of life, which is an essential aspect in assessing patients clinical status and prognosis. Nowadays, five types of cardiac pacing are recognised in clinical practice: - Endocardial right chambers pacing: the device is implanted in the subcutaneous subclavian area and it is connected to transvenous leads implanted in the right cardiac chambers, which detect intrinsic electrical activity and stimulate when needed; - Epicardial pacing: this procedure is often performed in conjunction with cardiac surgery; - Cardiac resynchronisation therapy (CRT): it delivers biventricular or left ventricular pacing in order to correct interventricular electromechanical dyssynchrony and to improve cardiac output; - Conduction system pacing: it stimulates the His bundle or the left bundle branch area downstream of the conduction block, in order to restore a physiological electromechanical activation. - Leadless pacing: via a percutaneous approach through a large-calibre vein, leadless device is placed inside the right ventricle. These pacing modalities have different possibilities to restore a normal cardiac electromechanical activation, resulting in different degrees of mechanical efficiency in terms of systolic output and diastolic pressures, with consequent effects on improvement/onset of heart failure and cardiopulmonary performance of our patients. Right ventricular pacing induces a dyssynchronous cardiac activation pattern that can lead to left systolic dysfunction and a consequent increased risk of death related to the development of heart failure. These observations led to the study of alternative cardiac pacing modalities since the 1990s, in order to improve the clinical outcome of patients with symptomatic bradyarrhythmias. The study of pathological ventricular activation due to left bundle-branch block represents the pathophysiological premise of cardiac resynchronisation in patients with systolic dysfunctional heart failure, and constitutes the developmental model for physiological pacing. CRT improves mortality and quality of life in patients with heart failure and reduced left ventricular ejection fraction. Typically left ventricular pacing is achieved by placing a catheter in the posterolateral area through a venous branch of the coronary sinus. Unfortunately, despite several years of experience in this field, clinical non-response to this therapy is observed in between 20% and 40% of patients, mostly due to the inability to reach the appropriate pacing site because of anatomical difficulties/absence of veins in the target area. Recently, conduction system pacing (CSP) has rapidly emerged as an alternative pacing modality to both right ventricular pacing (RVP) and CRT, in order to achieve a more physiological pacing. His bundle pacing (HBP) is considered the physiological pacing "par excellence", but the results in literature show rather frequent technical difficulties due to high pacing thresholds, inadequate ventricular signal amplitude for the detection of intrinsic cardiac activity, low success rate and risk of progression of conduction system pathology in patients with infranodal conduction defects. Left bundle area pacing has more recently emerged as a viable alternative to achieve physiological pacing with haemodynamic parameters similar to those of HBP, but with lower and stable pacing thresholds, ventricular signal amplitude adequate for the detection of intrinsic cardiac activity and high success rate. Several experiences with different pacing systems have been published, mainly single-centre studies with small sample sizes and different definitions of conduction system pacing success. In non-randomised comparative studies, and thus with methodological limitations, clinical superiority over conventional right ventricular pacing, and a substantial efficacy equivalent to CRT in patients with left bundle-branch block, has been shown, creating the preconditions for widespread use of the CSP. Considering, therefore, the widespread use of the latter technique and the high rate of implants that can potentially benefit from physiological pacing, evaluating safety, feasibility, timing and benefits becomes more crucial than ever. Therefore, the goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres. The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated. The investigators will collect clinical and procedural data from patients with an indication for permanent cardiac pacing who have consecutively undergone an implantable electronic device implant procedure at the Electrophysiology Laboratories of the participating centres over a period of 120 months from the time of approval with a follow-up of an equal 120 months. Patients will be classified according to the type of stimulation: 1. Right chambers endocardial pacing; 2. Cardiac resynchronisation therapy; 3. Conduction system pacing: 1. His bundle pacing 2. Left bundle branch area pacing. In addition, the efficacy and safety at 30 days, and the efficacy and safety at 6 and 12 months of the various pacing modalities, will be evaluated. The investigators defined efficacy at 30 days the presence of stable electrical parameters - or, if unstable, not requiring early re-intervention, the absence of cardiovascular hospitalizations and the absence of cardiovascular death. The investigators defined safety at 30 days the absence of procedural complications, such as haematoma requiring re-intervention or with haemoglobin loss >2gr/dl, pneumothorax, pericardial effusion requiring drainage, lead dislocation, cardiac implantable electronic device (CIED) infection or a re-intervention for any cause. Equally, the investigators defined efficacy at 6-12 months the presence of stable electrical parameters - or, if unstable, not requiring re-intervention, the absence of cardiovascular hospitalizations, the absence of cardiovascular death, the occurrence of heart failure, the occurrence or worsening of atrial or ventricular tachyarrhythmias. Therefore, the investigators defined safety at 6-12 months the proper functioning of the device, the absence of infection and the absence of re-intervention for any cause.
Phase
N/ASpan
626 weeksSponsor
University Hospital of FerraraGrosseto
Recruiting
Multicentre Prospective Observational Study of Acute Intoxications in Paediatric Age
Phase
N/ASpan
540 weeksSponsor
Meyer Children's Hospital IRCCSGrosseto
Recruiting
Reassessment of myocardIAL Bridge TOwards PeRsOnalized Medicine
TRIAL PROCEDURES Once MB is angiographically detected, eligible and consenting patients will be randomly assigned in a 1:1 ratio to receive a "standard approach" or a "full-physiology approach" during index CA. Index coronary angiography Coronary angiography will be performed through a radial or femoral approach. Unfractionated heparin (initial weight-adjusted intravenous bolus of 50-70 IU/kg, with repeat boluses to achieve an activated clotting time ∼250) will be administered in all patients. To fully expose all segments of the coronary arteries, at least 2 perpendicular projections for the right coronary artery (RCA) and 4 projections for the LAD will be taken. Intracoronary nitrates can be used (depending on blood pressure and, in any case, at the discretion of the Investigator) to increase the angiographic sensitivity in detecting the "milking effect". Physiological epicardial and microvascular assessment MB hemodynamic assessment will be performed using a diagnostic guidewire placed in the index vessel. Intravenous heparin (50-70 U/kg) should be administered to achieve therapeutic anticoagulation (activated clotting time ∼250 s). The innovative Abbott PressureWire™ X Guidewire will be used to measure pressure and temperature. The guidewire's wireless measurements are connected to an advanced platform (Coroventis‡ CoroFlow‡ Cardiovascular System) to measure physiological indices. Abbott's PressureWire™ X Guidewire and Coroventis‡ CoroFlow‡ Cardiovascular System are, nowadays, the only solution for the cath lab able to assess both epicardial vessel (i.e., FFR< 0.80) and microcirculation (i.e., CFR< 2.0 and IMR≥ 25). Epicardial assessment will include: - Resting Pd/Pa (n.v. > 0.92) - FFR after intravenous adenosine administration (n.v. > 0.80) - RFR (n.v. > 0.89) - FFR after intravenous dobutamine administration (n.v. > 0.75) FFR is defined as the mean distal pressure (Pd)/mean aortic pressure (Pa) across MB during maximal hyperemia, achieved by administration of intravenous (140 μg/kg/min) or intracoronary bolus (up to 200 µg) of adenosine. Pd/Pa was automatically calculated by current computational software as the ratio found in the pressure recording. A cut-off of 0.80 will be used to detect hemodynamic relevance. Inotropic stimulation to exalt the hemodynamic significance of MB will be performed with intravenous dobutamine infusion, in case of a negative functional assessment (Pd/Pa> 0.92, FFR> 0.80, RFR> 0.89). The infusion will be started at 5 μg/kg/min and increased by 5μg/kg/min every 5 minutes up to 20 μg/kg/min or until the patient develops symptoms or clear evidence of ischemia. An intravenous infusion of 1 mg atropine will be administered if the patient will not experience symptoms or signs of myocardial ischemia with 20 μg/kg/min of dobutamine infusion. An intravenous bolus of β-blocker (i.e., metoprolol 5 mg) will be administered at the end of the procedure to antagonize the effects of dobutamine. Microvascular assessment will include: - basal CFR (n.v. ≥ 2.0) and CFR after intravenous dobutamine administration (CFR-d) - basal IMR (n.v. < 25) and IMR after intravenous dobutamine administration (IMR-d) The coronary flow reserve and the microcirculatory resistance will be calculated using thermodilution thanks to the PressureWire™ X Guidewire. The thermodilution-based CFR cut-off value is 2.0. It is the ratio of the maximal or hyperemic flow down a coronary vessel to the resting flow. IMR is calculated as the product of distal coronary pressure at maximal hyperaemia multiplied by the hyperaemic mean transit time. Reduced CFR (< 2.0) and increased IMR (≥ 25) are representative of structural microvascular dysfunction (impaired endothelium-independent vasodilatation). ACH provocative test In order to unmask MB-related epicardial and/or microvascular CAS, ACH provocative test will be performed in case of absence of epicardial hemodynamic significance and structural microvascular dysfunction. Incremental doses of 20, 50, 100 and 200 μg of ACH will be infused over a period of 2 minutes into the index vessel (vessel with angiographic "milking effect") via the angiographic catheter, repeating CA after each Ach dose. The test will be performed with a continuous monitoring of symptoms, electrocardiogram (ECG), and angiographic evidence of spasm. Angiographic responses during the provocation test will be assessed in multiple orthogonal views to detect the artery spasm. If either complications and/or a positive response occurred, the test will be discontinued, and higher doses will be not administered. The test will be considered positive for epicardial CAS in the presence of focal or diffuse epicardial coronary diameter reduction ≥90% in comparison with the relaxed state following intracoronary nitroglycerine administration given to relieve the spasm, associated with the reproduction of the patient's anginal symptoms and ischemic ECG shifts. Microvascular spasm will be diagnosed when typical ischemic ST-segment changes and angina develop in the absence of epicardial coronary constriction (< 90% diameter reduction). Patients who will not experience angina, spasm, or ST-segment shifts will be considered to have a negative test response (normal coronary vasoreactivity). Similarly, patients who will experience ischemic ECG shifts without angina or patients with chest pain without ischemic ECG shifts will be considered to have a negative test response. Statistical analysis Statistical analysis will be performed using statistical software package Statistic for Data Analysis Stata 17 (64 bit; StataCorp, College Station, TX) and GraphPad Prism version 8.0.2 (GraphPad Software, San Diego, CA). Chi-square, Fisher's exact test and Kruskal Wallis test will be used to compare categorical variables. Continuous variables were listed as mean ± standard deviation (SD) and will be compared between groups using the Student's t-test, the Mann-Whitney U test, as appropriate. We will perform a 2-tailed analysis and consider a p-value ≤0.05 to be significant. With respect to the primary endpoint, all events occurring from randomization to the study end date will be counted. The number and rate of patients experiencing a primary endpoint will also be summarized. The proportion of patients remaining event-free over time will be displayed in the form of survival curves using the Kaplan-Meier method and analyzed using the log-rank test and the Gehan-Breslow-Wilcoxon test. With respect to secondary endpoints, a Cox proportional hazards model will be used, and estimates of the hazard ratios and their confidence intervals will be provided. In general, missing values will remain as missing, i.e., no attempt will be made to impute missing values and only observed values will be used in data analyses. An interim analysis will be performed on the primary endpoint when 50% of patients will have been randomized and completed the 6 months follow-up. The interim analysis will be performed by an independent statistician, blinded for the treatment allocation.
Phase
N/ASpan
107 weeksSponsor
Azienda Ospedaliero Universitaria Maggiore della CaritaGrosseto
Recruiting
RObotic Versus LAparoscopic Colectomy for DIverticulitis.
Background Over the past decade, there has been a growing interest in the use of robotic surgery for diverticular disease (DD). The evidence available in the literature is based on retrospective studies and two meta-analyses1,2. To date, the robotic approach offers significant advantages over laparoscopic surgery in terms of conversion rate and shortened hospital stay for the treatment of diverticular disease. The investigators aimed to evaluate whether elective robotic colectomy may offer some advantages over the laparoscopic approach for surgical treatment of diverticular disease performing a prospective multicenter study. Methods and Materials This is a multi-center, prospective, not-for-profit cohort study that will enroll patients undergoing elective or delayed urgent surgical treatment for left-sided colonic diverticular disease. The enrollment period will be one year, followed by one year of follow-up. The study will start in Juin 2023. Data will be collected in a prospective database using an easy to fill out Google form, also available on mobile devices. Several preoperative, intraoperative and postoperative outcomes will be analyzed. OUTCOMES Pre-Operative - Demographic Outcomes: Age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA), Charlson Comorbidity Index (CSI: https://www.mdcalc.com/calc/3917/charlson-comorbidity-index-cci) - Indications for surgery: - Complicated DD: colonic stenosis, abscess, fistula, others; - Recurrent DD: multiple episodes of diverticulitis affecting quality of life; - Planned vascular ligation (inferior mesenteric artery vs. sigmoid arteries) - Preoperative bowel preparation - Indication for minimally invasive approach pursued (Why Rob vs Lap) Intraoperative - Surgical approach (laparoscopic or robotic) - Intraoperative findings (sigmoid stenosis, stricture, adhesion, fistula) - Intraoperative complications (specify types) - Conversion to open approach - Operative times - Effective vessel ligation - Splenic flexure mobilization - Type of colon resection (sigmoidectomy, left colectomy, anterior rectal resection, Hartmann procedure) - Stoma (ileostomy vs. colostomy) - Associated procedures - Specimen extraction (midline, off midline, suprapubic or natural orifice) Postoperative - 30-day postoperative complications (Clavien-Dindo classification) - 30-day reoperation - 30-day readmission - Length of stay LOS - Time to return to work (days) - 30 days - Mortality - One-year follow-up Sample size The estimated sample sizes for the study using a proportion of 0.125 for Laparoscopic approach and a proportion of 0.074 for Robotic approach, and a risk of conversion rate OR=0.56 (IC95% 0.45-0.70), is at least 1450 patients (725 for the group - alpha = 0.0500, power = 0.9000, delta = 0.5600). MICE (Multivariate Imputation via Chained Equations) is the procedure used to impute missing data for explanatory variables. In this approach, instead of imputing all missing values with a single value (mean/median), the statistical information is derived from the median), it takes into account the statistical information derived from the distribution of the other variables. The missing values are considered as an outcome to be predicted. This allows to take into account the correct variability in the entire data set and to obtain estimates that are as unbiased as possible. Statistical Analysis The quantitative variables included in the study are expressed as mean ± standard deviation, median and range (distance between maximum and minimum values), both at the overall level and by surgical approach. The qualitative (categorical) variables are presented as percentages and absolute values, both at a general level and divided by surgical approach. It will be evaluated, if necessary, to perform a propensity score matching procedure between the two approaches (Rob and Lap), using the nearest neighbor matching technique, without replacement. Demographics, pre-operative and intra-operative characteristics are used in the propensity score logistic regression models to minimize selection bias, by assembling a matched cohort in which confounding factors are balanced between the two groups. In the matched cohort bivariate analyses are performed to .compare the primary and secondary outcomes between the two groups. The comparison between the quantitative variables of interest is performed by the two-tailed Student T-test (in case of heteroskedasticity of variances) or with nonparametric tests, such as the Mann-Whitney U test or theKruskal-Wallis test. The comparison between qualitative variables of interest is carried out to evaluate the association or not between them, through an extension of the chi-square test suitable for multicenter studies (the Cochran - Mantel - Haenszel test). For the entire cohort multivariate logistic regression models are performed to test the effect of surgical approach on primary and secondary outcomes. Ethics and dissemination The trial will be conducted in accordance with the Declaration of Helsinki and in compliance with the Good Clinical Practice, Principle E6 (R2). The study will be approved by the Ethics Committee of the coordinating center (Comitato Etico di Area Vasta Sud Est Dipartimento Politiche del Farmaco e Attività Farmaceutiche Segreteria Amministrativa) and then will be registered at ClinicalTrial.gov. Subsequently, all participating centers will receive approval to participate from the local institutional review board. Authorship for written publications will be confirmed for all participating investigators (2 investigators per center). Anonymized participant-level data sets will be made available upon reasonable upon reasonable request by contacting the principal investigator. Study results will be presented at international or national meetings and published in surgical journals.
Phase
N/ASpan
109 weeksSponsor
S.M. Misericordia HospitalGrosseto, Tuscany
Recruiting
A Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy in Local Advanced or Metastatic Non-small Cell Lung Cancer (WU-KONG28)
Phase
3Span
255 weeksSponsor
Dizal PharmaceuticalsGrosseto
Recruiting
TRanscatheter Aortic-Valve Implantation With or Without On-site Cardiac Surgery: the TRACS Trial
TRACS is an all-comer, prospective, randomized, multicenter, open-label trial with blinded adjudicated evaluation of outcomes (PROBE). The TRACS trial will involve centers without on-site cardiac surgery, but with experienced operators already performing TAVI at the referring center with on-site cardiac surgery. Thus, participating centers and their study TAVI operators must follow selective criteria for eligibility. Participants will be recruited after Heart Team indication to TAVI procedure. The eligibility of each single patient to the study MUST BE CONFIRMED and VALIDATED by unanimous decision of the Heart Team. Study patients will be randomized in a 2:1 fashion to TAVI procedure performed by the same experienced operators either in the center without on-site cardiac surgery or in the referring center with on-site cardiac surgery.
Phase
N/ASpan
261 weeksSponsor
Azienda Usl di BolognaGrosseto
Recruiting
In-hospital Stellate Ganglion Block for Arrhythmic Storm
This is a multicenter international observational retrospective and prospective short term (24 hours) longitudinal study, promoted and coordinated by the Fondazione IRCCS Policlinico San Matteo (Pavia, Italy). Materials and methods All the patients who will meet the inclusion criteria will be enrolled in the study. Conscious patients with a sufficient free interval between arrhythmic relapses will sign the informed consent for the procedure and for data collection (attached at the study protocol) before the procedure. In case of unconscious patients the medical doctor will perform the procedure being in an emergency situation and the inform consent for data collection will be signed afterward once possible. Inclusion criteria: All the patients presenting with an arrhythmic storm defined as more than three sustained ventricular arrhythmias in 24 hours refractory to the standard medical treatment. Exclusion criteria - A previous history of cardiac sympathicectomy - Having a neck judged by the doctor as non-suitable for the procedure (previous neck surgery, previous burns, presence of large scars, thyroid goiter) PSGB technique Both the two approaches present in literature and commonly used for this technique are allowed for the study: - The "anatomical" approach which consist in the identification of the Chassaignac's tubercle that represents the point of needle insertion - The "echo-guided" approach Regardless to the approach (anatomical or echo-guided) the doctor will be able to choose, according to the clinical characteristics of the patients, whether to perform a single shot injection of anesthetic or a continuous infusion of anesthetic. In the second case a catheter will be left in place and connected to an infusion pump. Study endpoints The primary endpoint is the effectiveness of the PSGB expressed by the reduction of arrhythmic relapses [number of Direct Current (DC) shocks or Anti-Tachycardia Pacing ATP] in the 12 hours immediately after the PSGB as compared to the 6 hours immediately preceding the PSGB of at least 50%. The secondary endpoints are: 1. The comparison of the number of shocks 12h before and 12h after the procedure 2. The feasibility of the procedure expressed as the number of complications within 12 hours from the procedure. The following complications will be considered: - Simple hematoma - Symptoms due to anesthetic absorbance - Hematoma requiring intervention - Intravascular injection without complication - Intravascular injection with complication - Brachial plexus damage - Simple vascular damage - Vascular damage requiring intervention 3. The comparison of the effectiveness endpoint in patients with and without the appearance of anisocoria 4. The comparison of effectiveness between patients who will receive "anatomical" PSGB and those who will receive echo-guided PSGB 5. The comparison of effectiveness between patients who will receive anaesthetic infusion in the site of PSGB as compared to those who will not. Statistics Sample size: The investigators plan to enroll patients satisfying the inclusion/exclusion criteria over a time horizon of 5 years. Based on our previous experience over the previous 18 months (enrollment of 8 patients) about 5 patients per year are though to be enrolled, thus reaching a sample size 33 patients in the Pavia Center. The success is effectiveness to be not less then 90%, based on our historical cohort. This will yield a confidence interval of 76% to 98%, corresponding to a precision of 11%. Also, with this sample size it will be able to exclude an effectiveness of 70% (considered as the lower bound of acceptability) with a power of 94% (alpha 2-sided 5%). With the inclusion of further centers, the increased sample size will allow an increased precision of the estimates; for instance for 100 patients precision would be 6.5%. Statistical analysis: Data will be described with the mean and standard deviation or the median and 25th-75th percentile if continuous and counts and percent if categorical. For the analysis of the primary endpoint the rate of effectiveness together with its 95% exact binomial confidence interval will be computed. Data management Data will be collected using the REDCap platform. A personal and password protected account will be created for each investigator who will be able to access only to the data form his/her center.
Phase
N/ASpan
470 weeksSponsor
IRCCS Policlinico S. MatteoGrosseto
Recruiting
A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE
Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. Patients with intact GI and GU cancer have increased bleeding risk with oral direct anticoagulants (DOACs), Guidelines advice caution with those DOACs or state preference for low molecular weight heparin (LMWH) in this population. The ANT-008 study will compare treatment with abelacimab monthly administration to LMWH daily subcutaneous (sc) administration over 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months
Phase
3Span
231 weeksSponsor
Anthos Therapeutics, Inc.Grosseto
Recruiting
A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE
Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. The two most common treatments today are low molecular weight heparin (LMWH) and direct anticoagulants (DOACs), in which each has limitations. DOACs are administered orally and are seen as a more convenient alternative though associated with bleeding risk; further, some cancer patients have difficulty swallowing or develop vomiting which leads to unpredictable pharmacodynamic effects with oral therapy. The ANT-007 study will compare treatment with abelacimab monthly administration to apixaban twice daily administration over a 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months
Phase
3Span
252 weeksSponsor
Anthos Therapeutics, Inc.Grosseto
Recruiting
Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment Resected Colon Cancer Patients
This is a prospective, open-label, multicentre study, including two phase II randomized trials. In Part 1 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after surgery will be randomized to receive FOLFOX for 12 cycles or CAPOX for 8 cycles (at investigator choice) versus FOLFOXIRI for 12 cycles. In Part 1 target-driven resected stage III and high-risk stage II HER2+ and RAS wild-type colon cancer patients with positive ct-DNA after surgery will receive Trastuzumab and Tucatinib plus FOLFOX for 12 cycles. In Part 2 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after the end of a fluoropyrimidine and oxaliplatin-based adjuvant therapy - either in the frame or outside of Part 1 - will be randomized to receive observation or Trifluridine/Tipiracil for 6 cycles.
Phase
2Span
242 weeksSponsor
Gruppo Oncologico del Nord-OvestGrosseto
Recruiting