[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657641":3},{"organization":4,"outcomesModule":7,"designInfo":39,"detailedDescription":47,"studyPopulation":38,"armGroups":48,"interventions":59,"overallOfficials":38,"centralContacts":38,"locations":63,"responsibleParty":96,"collaborators":99,"id":125,"slug":126,"hasResults":127,"nctId":128,"briefTitle":129,"officialTitle":130,"acronym":131,"eligibilityCriteria":132,"healthyVolunteers":127,"sex":133,"minAge":134,"maxAge":38,"enrollmentInfo":135,"targetDuration":38,"studyType":138,"phases":139,"briefSummary":141,"conditions":142,"keywords":149,"overallStatus":156,"whyStopped":38,"lastUpdateSubmitDate":157,"lastUpdatePostDateStruct":158,"startDateStruct":161,"completionDateStruct":163,"leadSponsor":165,"locationsCount":166},{"fullName":5,"class":6},"Fondazione IRCCS Policlinico San Matteo di Pavia","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":38},[9],{"measure":10,"description":11,"timeFrame":12},"Complete Suppression of treated VAs (ATP\u002FDC shock) within 3 hours","Proportion of patients with complete suppression of treated VA (with ATP, internal DC shock or external DC shock) during the first three hours after treatment.","within 3 hours from treatment",[14,17,20,24,28,32,35],{"measure":15,"description":16,"timeFrame":12},"Time to first recurrence","The time to first recurrence within 3 hours from index treatment administration",{"measure":18,"description":19,"timeFrame":12},"Treated ventricular arrhythmias in the first 3 hours","The per patient rate of treated VAs in the first three hours within 3 hours from treatment administration (number of treated VAs per patient).",{"measure":21,"description":22,"timeFrame":23},"Number of ventricular arrhythmias 3 hours before and after treatment","The per patient rate of treated VAs in the first three hours after treatment administration and in the previous three hours (number of treated VAs per patient).","±3 hours from treatment administration",{"measure":25,"description":26,"timeFrame":27},"Number of crossover","The proportion of patients in the \"PSGB-first\" group who need AAD infusion and the proportion of patients in the \"Amiodarone-first\" group who need PSGB (cross-over rate)","In the first 12 hours after treatment administration",{"measure":29,"description":30,"timeFrame":31},"Number of treated ventricular arrthythmias in the first 12 hours after treatment","The per patient rate of treated VAs in the first twelve hours after treatment administration (number of treated VA per patient).","at 12 hours post-treatment",{"measure":33,"description":33,"timeFrame":34},"Time to in-hospital death","from index treatment to hospital discharge (maximum 30 days)",{"measure":36,"description":36,"timeFrame":37},"Time to death within one month","from index treatment to 1 month follow-up",null,{"allocation":40,"interventionModel":41,"interventionModelDescription":42,"primaryPurpose":43,"observationalModel":38,"timePerspective":38,"maskingInfo":44},"RANDOMIZED","PARALLEL","Randomised, double-arm (parallel groups), open label, multicentre, adaptive superiority, controlled Clinical Trial.","TREATMENT",{"masking":45,"maskingDescription":46,"whoMasked":38},"NONE","The event adjudication committee will blindly adjudicate the arrhythmics events","Electrical storm (ES) is a critical manifestation of electrical instability of the heart, characterized by clustered episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) that trigger repeated interventions by implantable cardioverter-defibrillators or require external defibrillation. Beyond the immediate risk of hemodynamic collapse and cardiac arrest, ES is associated with repeated myocardial injury from shocks, psychological distress, prolonged intensive care stays, and increased short- and medium-term mortality. Contemporary cohorts indicate that ES occurs in approximately 5% of patients with an ICD implanted for primary prevention and in up to 25% of those implanted for secondary prevention, underscoring its clinical relevance.\n\nThe pathophysiology of ES involves a dynamic interaction between an arrhythmogenic substrate, often related to structural heart disease or channelopathies, and transient triggers that promote initiation and maintenance of ventricular arrhythmias. Among these triggers, heightened sympathetic activity plays a central role. Experimental work beginning in the late 1960s demonstrated that acute myocardial ischemia activates sympathetic afferents before electrocardiographic changes become evident, and that direct stimulation of the left stellate ganglion can induce delayed afterdepolarizations and lower the threshold for VF. Conversely, left cardiac sympathetic denervation raises the fibrillation threshold and reduces arrhythmic vulnerability. These observations established the conceptual foundation for targeting the sympathetic nervous system in the management of malignant ventricular arrhythmias.\n\nDespite this well-characterized pathophysiology, current guideline-directed management of ES remains anchored in pharmacological antiarrhythmic therapy, with intravenous amiodarone as the most widely adopted first-line agent. Amiodarone is recommended by European and American guidelines for recurrent VT\u002FVF and advanced life support scenarios. However, its onset of action is not immediate, efficacy in refractory ES is variable, and its administration is not devoid of acute adverse effects, including hypotension, bradycardia, and potential proarrhythmia. In patients with recurrent shocks despite pharmacological therapy, additional options such as deep sedation, general anaesthesia, catheter ablation, or surgical sympathetic denervation may be considered, but these approaches are not universally available, may require significant resources, and are not always feasible in unstable patients.\n\nIn this context, percutaneous stellate ganglion block (PSGB) has emerged as a rapid, minimally invasive neuromodulatory intervention that can be performed at the bedside with equipment commonly available in cardiology and critical care settings. PSGB involves percutaneous injection of local anaesthetics near the left stellate ganglion, resulting in temporary blockade of sympathetic efferent fibres innervating the heart. Two main techniques have been described: an anterior anatomical approach based on palpation of the Chassaignac tubercle at the C6 level, and a lateral ultrasound-guided approach targeting the prevertebral space over the longus colli muscle. Both techniques have been employed in observational studies with comparable efficacy and safety profiles.\n\nClinical evidence supporting PSGB in ES has accumulated over the past two decades. Early case reports described successful termination of drug-resistant VT and VF following left PSGB in patients with prolonged QT interval and structural heart disease. Subsequent monocentric retrospective series consistently reported marked reductions in arrhythmic burden and ICD shocks after PSGB, often with complete suppression of treated arrhythmias in a substantial proportion of patients. More recently, two multicentre observational studies have provided more robust evidence. The STAR study, promoted by our group and involving 19 Italian centres, enrolled 131 patients who underwent 184 PSGB procedures. In that study, 92% of patients achieved a reduction of at least 50% in treated ventricular arrhythmias in the 12 hours following the last procedure, with a median reduction of 100%. A significant decrease in arrhythmic episodes was observed both in per-procedure analysis comparing the hour before and after each block, and in per-patient analysis comparing the 12 hours before and after the intervention. Importantly, only one major complication occurred, supporting an excellent safety profile even in a population frequently receiving antiplatelet and anticoagulant therapy. A second multicentre study from the United States and Czech Republic confirmed these findings, demonstrating significant reductions in VT\u002FVF episodes and defibrillation events in the 24 hours following PSGB.\n\nDespite this accumulating evidence, several critical gaps remain. First, all published studies to date have been observational, limiting the strength of causal inference and leaving open the possibility of selection bias and confounding. Second, PSGB has been evaluated almost exclusively as an add-on therapy in patients already receiving continuous intravenous antiarrhythmic drugs, leaving unanswered the question of whether PSGB could replace or precede pharmacological therapy as the initial intervention. Third, no randomized controlled trial has directly compared PSGB with standard antiarrhythmic therapy in the acute management of ES. Two randomized trials are currently registered, but in neither is PSGB administered as first-line treatment; one evaluates PSGB versus sham in patients already deemed candidates for the procedure on top of standard care, and the other compares repeated PSGB every three days with standard treatment in medically refractory VT.\n\nPreliminary data from an updated analysis of the STAR dataset provide indirect support for the potential role of PSGB as first-line therapy. In a subgroup of 26 patients who received PSGB early, before initiation of intravenous antiarrhythmic infusion, the reduction in treated ventricular arrhythmias was comparable to that observed in patients who received PSGB after or during antiarrhythmic therapy. Approximately 80% of patients in both groups (early and delayed PSGB) remained free from arrhythmias in the three hours following the procedure. These observations, together with the rapid onset of action of PSGB and its favourable safety profile, suggest that earlier implementation of sympathetic block could potentially reduce the number of shocks delivered, preserve left ventricular function, and improve short-term outcomes.\n\nThe adaptive design of the study incorporates two pre-specified interim analyses to allow for early termination based on futility or efficacy. At 30% of the planned enrollment, a futility analysis will assess whether the observed treatment effect is sufficiently promising to justify continuation. At 70% of enrollment, an efficacy analysis will evaluate whether the experimental intervention has already demonstrated superiority within corrected statistical boundaries. This approach, based on Pocock error-spending boundaries for futility and O'Brien-Fleming boundaries for efficacy, maintains the overall type I error rate at 5% while optimizing resource utilization and ethical conduct. Randomization will be stratified by prior administration of metoprolol, reflecting the class I recommendation for beta-blocker therapy in this setting and ensuring balanced distribution of this potentially prognostic factor across treatment arms.\n\nFrom a methodological perspective, the choice of a three-hour primary endpoint window reflects a balance between several considerations. A shorter window might overestimate the effect of PSGB relative to amiodarone, given that the amiodarone loading dose requires approximately 30 minutes to infuse and additional time to exert its full antiarrhythmic effect. A longer window, conversely, could increase the likelihood of crossover between treatment arms in case of life-threatening recurrences, introduce bias from spontaneous resolution of ES, and dilute the comparison of the initial treatment strategy. The three-hour period captures the phase of highest arrhythmic risk and aligns with the expected duration of action of the local anaesthetics used for PSGB.\n\nBeyond its immediate clinical implications, the STAR 2 study has potential regulatory and translational relevance. The local anaesthetics employed for PSGB, lidocaine and bupivacaine, are approved for peripheral nerve blocks but are used off-label for antiarrhythmic purposes via stellate ganglion block in many jurisdictions. Demonstration of superiority of PSGB as first-line therapy in a randomized controlled trial could support future efforts to expand the indication for use of these agents to include cardiac neuromodulation for the treatment of ventricular arrhythmias, potentially facilitating broader adoption of this technique and standardization of training and procedural standards.\n\nThe multicentre nature of the trial, with participation of both high-volume and lower-volume centres, and the implementation of a standardized training program for operators, aim to ensure that the findings are generalizable across diverse clinical settings. The training program, developed by the coordinating centre, includes theoretical instruction on anatomical landmarks, ultrasound guidance, and management of potential complications, as well as hands-on practice using anatomical models and simulated procedures. This approach seeks to harmonize procedural quality across sites while allowing operators to select the technique (anatomical or ultrasound-guided) most consistent with their expertise and local resources.\n\nBy addressing a critical gap in the evidence and evaluating a rapid, minimally invasive intervention in a high-risk population with limited therapeutic options, the STAR 2 study has the potential to influence future guideline recommendations and reshape the acute management algorithm for patients presenting with electrical storm.",[49,53],{"label":50,"type":51,"description":52,"interventionNames":38},"Amiodarone first (SoC)","NO_INTERVENTION","Control group receiving intravenous amiodarone infusion as first-line treatment. According to guidelines Amiodarone is the most commonly used intravenous antiarrhythmic drug and represents the current standard of care.",{"label":54,"type":55,"description":56,"interventionNames":57},"L-PSGB first","EXPERIMENTAL","Intervention group receiving left percutaneous stellate ganglion block (L-PSGB) as first-line treatment. The procedure consists of a single injection (bolus), at the level of the left-sided Chassaignac's tubercle (C6), of a combination of 200 mg lidocaine and 50 mg bupivacaine. Repetition of PSGB can be considered in case of arrhythmic recurrence within the first three hours.",[58],"Drug: L-PSGB first",[60],{"type":61,"name":54,"description":56,"armGroupLabels":62,"otherNames":38},"DRUG",[54],[64],{"facility":65,"status":38,"city":66,"state":67,"zip":68,"country":69,"countryCode":70,"cosmosGeoPoint":71,"geoPoint":76,"contacts":77},"Cardiology Division, Fondazione IRCCS Policlinico San Matteo of Pavia","Pavia","PV","27100","Italy","IT",{"type":72,"coordinates":73},"Point",[74,75],9.15917,45.19205,{"lat":75,"lon":74},[78,84,88,91,94],{"name":79,"role":80,"phone":81,"phoneExt":82,"email":83},"Simone Savastano, MD (study PI)","CONTACT","+39 0382501590","+39","s.savastano@smatteo.pv.it",{"name":85,"role":80,"phone":86,"phoneExt":82,"email":87},"Alessia Currao, Clin. PharmD. (CRC)","+39 038250 -1590\u002F-3739","a.currao@smatteo.pv.it",{"name":89,"role":90,"phone":38,"phoneExt":38,"email":38},"Simone Savastano, MD","PRINCIPAL_INVESTIGATOR",{"name":92,"role":93,"phone":38,"phoneExt":38,"email":38},"Enrico Baldi, MD","SUB_INVESTIGATOR",{"name":95,"role":93,"phone":38,"phoneExt":38,"email":38},"Roberto Rordorf, MD",{"type":90,"investigatorFullName":97,"investigatorTitle":98,"investigatorAffiliation":5,"oldNameTitle":38,"oldOrganization":38},"Simone Savastano","Principal Investigator",[100,102,104,107,109,111,113,115,117,119,121,123],{"name":101,"class":6},"A.O.U. Città della Salute e della Scienza - Molinette Hospital",{"name":103,"class":6},"University Hospital Padova",{"name":105,"class":106},"Azienda Usl di Bologna","OTHER_GOV",{"name":108,"class":6},"Azienda USL Toscana Centro",{"name":110,"class":6},"Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria",{"name":112,"class":6},"Azienda Sanitaria Locale N.1 dell'Umbria",{"name":114,"class":6},"Azienda Ospedaliera Brotzu",{"name":116,"class":6},"Azienda Ospedaliera di Perugia",{"name":118,"class":6},"Azienda Ospedaliera Niguarda Cà Granda",{"name":120,"class":6},"San Raffaele University Hospital, Italy",{"name":122,"class":6},"Centro Cardiologico Monzino",{"name":124,"class":6},"Ospedale San Donato","100657641","phase-3-percutaneous-stellate-ganglion-block-as-first-line-treatment-in-patients-with-electrical-storm-the-star-2-study-100657641",false,"NCT07841080","Percutaneous Stellate Ganglion Block as First Line Treatment in Patients With Electrical Storm: the STAR 2 Study","A Multicentre Randomised Study on Percutaneous Stellate Ganglion Block as First Line Treatment in Patients With Electrical Storm: the STAR 2 Study.","STAR 2","Inclusion Criteria:\n\n* Age ≥ 18 years\n* More than 3 episodes of fast-VT\u002FVF treated by the internal or external defibrillator in the 12 hours before randomization and at least one in the three hours before.\n* Fast-VT or FV requiring internal or external treatment\n* Any structural heart disease\n* Acute or choric coronary disease\n* CPVT\n\nExclusion Criteria:\n\n* Brugada syndrome or early repolarization syndrome\n* Neck judged unfeasible for the procedure by the clinicians\n* Previous heart transplantation\n* Previous surgical sympathetic denervation\n* Previous ablation of the stellate ganglion block\n* Ongoing treatment with intravenous AAD drugs. Enrolment may be possible under certain circumstances (see Table 3 page 62-63) in case of recurrences after discontinuation\n* Refractory cardiac arrest\n* Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within the 5 half-lives of the study drugs whichever is longer\n* Pregnancy or breastfeeding\n* Known allergy or hypersensitivity or previous idiosyncrasy to amiodarone, lidocaine, bupivacaine or to any of the excipients\n* Contraindications to amiodarone or other study drugs (e.g. QT interval prolongation or known Long-QT syndrome, sick sinus syndrome, without a pacemaker; second- or third-degree AV block, without a pacemaker, active hyperthyroidism, severe hypotension, porphyria, untreated pheochromocytoma)","ALL","18 Years",{"count":136,"type":137},180,"ESTIMATED","INTERVENTIONAL",[140],"PHASE3","Electrical storm (ES) is a life-threatening condition characterized by recurrent episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) requiring anti-tachycardia pacing or defibrillator shocks. Despite advances in management, ES remains associated with high morbidity and mortality, and current pharmacological options are often insufficient or slow-acting.\n\nThe STAR 2 study is a multicentre, randomized, open-label, adaptive superiority trial designed to evaluate whether percutaneous stellate ganglion block (PSGB) as first-line therapy is superior to intravenous amiodarone in patients with ES. The primary hypothesis is that PSGB administered as initial treatment will result in a higher proportion of patients achieving complete suppression of treated ventricular arrhythmias during the first three hours after treatment compared with intravenous amiodarone.\n\nAdult patients presenting with electrical storm, defined as three or more episodes of fast VT\u002FVF (cycle length \\\u003C400 ms) treated by internal or external defibrillator within the preceding 12 hours, including at least one episode in the three hours before randomization, will be eligible for participation. Patients will be randomly assigned in a 1:1 ratio to receive either PSGB or intravenous amiodarone as first-line treatment.\n\nIn the intervention arm, patients will undergo left PSGB using a combination of 200 mg lidocaine and 50 mg bupivacaine injected percutaneously at the level of the left stellate ganglion. The procedure may be repeated once within the first three hours in case of arrhythmic recurrence, without exceeding maximum recommended doses. In the control arm, patients will receive intravenous amiodarone according to a standardized protocol consisting of a 300-mg loading dose over 30 minutes followed by 900 mg infused over 18-24 hours.\n\nThe primary outcome is the proportion of patients with complete suppression of treated ventricular arrhythmias (defined as VT\u002FVF episodes requiring anti-tachycardia pacing, internal cardioverter-defibrillator shock, or external defibrillator shock) during the first three hours after treatment administration. Secondary outcomes include time to first recurrence of ventricular arrhythmia within three hours, per-patient rate of treated ventricular arrhythmias in the first three and twelve hours after treatment, crossover rate between treatment arms, survival to hospital discharge, and survival at one month. Safety outcomes will include procedure- and drug-related complications and adverse events.\n\nThe study plans to enroll up to 180 patients across multiple centres. An adaptive design with pre-specified interim analyses for futility and efficacy will be employed, allowing for early termination if predefined statistical boundaries are crossed. Participants will be followed throughout hospitalization and for 30 days after discharge.\n\nThis trial aims to provide robust evidence on the comparative effectiveness and safety of PSGB versus standard antiarrhythmic therapy when used as first-line treatment in patients with electrical storm, potentially supporting a shift in current management strategies.",[143,144,145,146,147,148],"Electrical Storm","VT","VF","Ventricular Arrhythmia","Ventricular Tachycardia (VT)","Ventricular Fibrillation",[150,151,152,153,154,155],"PSGB","stellate ganglion","percutaneous stellate ganglion block","electrical storm","ventricular arrhythmias","VA","NOT_YET_RECRUITING","2026-09-24",{"date":159,"type":160},"2026-09-29","ACTUAL",{"date":162,"type":137},"2026-10-01",{"date":164,"type":137},"2029-12-31",{"name":5,"class":6},1]