Dueville, Italy
Diagnosis and Outcomes of Placental Accretism
Currently, the management of cases of placental accretism/percretism is not standardized. This study could help in assessing maternal and fetal outcomes related to the different therapeutic strategies applied in the clinical cases under study so that their management can be standardized in the near future. This is a retrospective and prospective, national multicenter study. Patients will be treated according to clinical practice. The main instrumental findings of cases of suspected accretism will be collected and analyzed, and the progression of pregnancy and postpartum (by means of laboratory and instrumental tests) will be evaluated in order to define the outcomes of conservative management (cesarean section with placenta in situ) versus more radical management (cesarean section and concomitant hysterectomy). In particular, clinical trends (by means of assessment of vital parameters, laboratory tests, ultrasound images or instrumental examinations) in pregnancy, in the immediate postoperative period and during subsequent outpatient follow-up visits will be analyzed. In general, in the absence of complications, visits will be performed twice a week during pre-partum. Postpartum follow-up is not standardized, as it will depend strictly on the procedure performed and the occurrence or absence of complications. There are no questionnaires and/or rating scales.
Phase
N/ASpan
181 weeksSponsor
IRCCS Azienda Ospedaliero-Universitaria di BolognaReggio Emilia
Recruiting
Multicenter Retrospective Observational Study of Relapsed Diffuse Large B-Cell Lymphoma Presenting As Indolent Lymphoma
Phase
N/ASpan
106 weeksSponsor
Azienda Unita Sanitaria Locale Reggio EmiliaReggio Emilia
Recruiting
Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants
Phase
N/ASpan
313 weeksSponsor
University of L'AquilaReggio Emilia
Recruiting
Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants
Phase
N/ASpan
157 weeksSponsor
Insel Gruppe AG, University Hospital BernReggio Emilia
Recruiting
Retrospective Analysis of Patients With Metastatic Renal Cell Carcinoma Treated With CABOzantinib
The aim of this study is to describe the genomic profiling of patients with metastatic renal cell carcinoma (mRCC) who are long-lasting responders to treatment with cabozantinib and patients who are not long-lasting responders to the cabozantinib treatment. The study plan to enroll about 80 patients in 10 Italian centers: Group A: 40 patients defined as long-lasting responders (PFS ≥ 9 months) Group B: 40 patients defined as primary refractories to cabozantinib (PFS ≤ 3 months) Tissue samples from nephrectomy or from a metastatic site will be used to perform genomic profiling not older than 5 years.Tissue should be formalin-fixed, paraffin-embedded (FFPE). Genomic profiling will be performed with a hybrid capture-based next-generation sequencing assay (FoundationONE). The sample will be assayed for all coding exons of 324 cancer-related genes plus select introns from 34 genes that are frequently rearranged in cancer. Sequencing will be performed to a mean exon coverage depth of >500X. The resulting sequences will be analyzed for all classes of genomic alteration, including short variant alterations, copy number alterations, and selected gene fusions or rearrangements.
Phase
N/ASpan
57 weeksSponsor
Gruppo Oncologico Italiano di Ricerca ClinicaReggio Emilia
Recruiting
Reggio Emilia
Recruiting
Thromboembolic and Hemorrhagic Complications of Anticoagulant Treatment in Patients With CAT
The study is classified as an observational study involving the use of medication, spontaneous, multicentric, retrospective, and prospective for adult patients with a diagnosis of venous thromboembolism in the context of neoplasia, followed at the SSD Angiology and Coagulation Disorders of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and The Cardiovascular Medicine Department, specifically the Angiology Unit, of the IRCCS Arcispedale S. Maria Nuova in Reggio Emilia. The study, including data analysis, is expected to conclude by 31/12/2027. Patients have been and will be treated according to clinical practice, in accordance with the physician's judgment and the information provided in the technical datasheet of each product used for any concomitant therapies administered as per clinical practice. The diagnostic-therapeutic pathway for patients will not be influenced in any way by the results of the tissue tests performed for the purposes of the study. Additionally, patients have been and will be followed according to the usual schedule defined by current clinical practice and will undergo all standard diagnostic investigations, both invasive and non-invasive, as prescribed by current clinical practice. All adult patients with a diagnosis of venous thromboembolism in the context of neoplasia, followed at the SSD Angiology and Coagulation Disorders of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and The Cardiovascular Medicine Department, specifically the Angiology Unit, of the IRCCS Arcispedale S. Maria Nuova in Reggio Emilia, will be enrolled from 01/01/2016 to 30/06/2027. Each patient will be followed according to standard clinical-care practice, with a follow-up of at least 6 months considered for the purposes of the study. Considering that the monthly attendance of patients at the Consultation Clinic of the SSD Angiology and Coagulation Disorders of the IRCCS AOUBO and The Cardiovascular Medicine Department, specifically the Angiology Unit, of the IRCCS Arcispedale S. Maria Nuova in Reggio Emilia is approximately 50 patients, based on the inclusion/exclusion criteria, it is estimated that about 1,000 patients with a diagnosis of VTE in the context of neoplasia can be enrolled. This sample size is considered sufficient to achieve the primary objective of the study. The primary objective is to evaluate the frequency of thrombotic and hemorrhagic complications during treatment with low molecular weight heparin or direct oral anticoagulants in patients with venous thromboembolism and solid and hematological neoplasms, followed in outpatient care at the SSD Angiology and Coagulation Disorders of the IRCCS AOUBO and The Cardiovascular Medicine Department, specifically the Angiology Unit, of the IRCCS Arcispedale S. Maria Nuova in Reggio Emilia, following the initiation of anticoagulant therapy (LMWH or DOACs). The secondary objectives are: - To identify risk factors for hemorrhagic complications and bleeding risk during anticoagulant treatment for CAT, - To assess the applicability and reliability of a score, which is not currently used in clinical practice, without affecting the care process and clinical decisions, in a prospective cohort of patients with CAT. The data available in the literature concern the use of anticoagulants (LMWH or DOACs) in patients with a confirmed diagnosis of venous thromboembolism in the context of neoplasia. However, it is necessary to stratify these patients in order to identify those who are more or less at risk of complications, in order to provide a more targeted therapeutic approach.
Phase
N/ASpan
626 weeksSponsor
IRCCS Azienda Ospedaliero-Universitaria di BolognaReggio Emilia
Recruiting
Integrative "Omics" Approaches for Leukemia Target Identification and Matched Therapeutic Intervention
Phase
N/ASpan
157 weeksSponsor
Azienda Ospedaliero-Universitaria di ParmaReggio Emilia
Recruiting
Atezolizumab and Rechallenge Chemotherapy in Relapsed Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC).
The CARRY-ON study is a multicenter, prospective, open-label single-arm phase II trial, designed to seek for a signal of efficacy of continuing PD-L1 inhibition in patients with sensitive relapse ES-SCLC by adding atezolizumab to rechallenge carboplatin-etoposide chemotherapy. The trial is planned to enroll 142 patients with sensitive relapse ES-SCLC from 25 Italian centers. Sensitive relapse is defined as SCLC relapsed or progressed to first-line chemo-immunotherapy with PD-L1 inhibition (with either atezolizumab or durvalumab) at least 60 days after the last chemotherapy administration. Eligible patients will receive re-challenge chemotherapy (either carboplatin AUC 4 on day 1 plus etoposide 80 mg/m2 days 1-3 or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 days 1-3, at investigator's choice) plus atezolizumab 1200 mg flat dosing on day 1 every 3 weeks until PD, unacceptable toxicity or to a maximum of 4 cycles (induction phase) followed by atezolizumab 1200 mg flat dosing every 3 weeks (maintenance phase) until completion of 1 year of maintenance (up to 18 cycles), progressive disease, unacceptable toxicity, patient refusal or loss of clinical benefit (investigator's choice), whichever occur first. Subjects will attend clinical visits at regular intervals to receive trial treatment and for efficacy and safety assessments. All subjects will be monitored continuously for any AE while on study treatment. Radiological assessment will be performed by computed tomography (CT) scan at week 6 (± 7 days), at week 12 (± 7 days) and every 12 weeks (± 7 days) thereafter. The duration of the study is expected to be a maximum of 45 months. The study recruitment period is expected to be approximately 24 months, maximum treatment duration will be 15 months (3 months of induction and 12 months of maintenance), and subsequent survival follow-up will be a maximum of 6 months.
Phase
2Span
227 weeksSponsor
Gruppo Oncologico Italiano di Ricerca ClinicaReggio Emilia
Recruiting
Italian Anderson Fabry Disease Cardiovascular Registry
1. Introduction Anderson-Fabry Disease (AFD) is a multisystemic lysosomal storage disorder with X-linked inheritance (Online Mendelian Inheritance in Man [OMIM] number 301500) caused by a total or partial deficiency of the enzyme α-galactosidase A (α-Gal A), encoded by the GLA gene (Xq22.1). The deficiency of α-Gal A leads to the accumulation of neutral glycosphingolipids, particularly globotriaosylceramide (Gb3) and galactosylceramide, in various cell types and tissues. The continuous accumulation of these molecules results in progressive cellular dysfunction, triggering inflammatory and pro-fibrotic phenomena that cause organ dysfunction. The clinical manifestations and age of onset of the disease are highly variable, and symptoms/signs often appear only after a degree of irreversible damage has already occurred. The classic form of AFD is the most severe clinical phenotype and predominantly affects males with null or minimal residual enzymatic activity (<1% of normal values). Symptoms begin early during childhood or adolescence and include acroparesthesias, angiokeratomas, telangiectasias, gastrointestinal disturbances, corneal alterations (cornea verticillata), proteinuria, renal insufficiency, hypo/hyperhidrosis, and hearing loss. Later in adulthood, progressive cardiac and cerebrovascular involvement may occur. Patients with atypical or late-onset variants generally develop the disease later (from the third to the seventh decade of life) compared to those with the classic form. The clinical picture is generally dominated by the involvement of a single organ, most frequently the heart. The measurement of residual enzymatic activity of α-Gal A is sufficient to establish a diagnosis in males. However, it is important to identify the specific genetic mutation to determine the disease phenotype and exclude benign polymorphisms that may cause reduced enzymatic activity levels. In females, genetic diagnosis is indispensable, as residual enzymatic activity often falls within the normal range. The treatment of AFD is based on compensating for the deficient enzymatic activity through enzyme replacement therapy (ERT) and managing the disease's symptoms and complications. More recently, an oral chaperone therapy capable of increasing residual enzymatic activity has been approved, though it is only effective for certain mutation types. Given the multisystemic involvement in AFD patients, longitudinal multispecialty evaluation is necessary, including cardiology, nephrology, neurology, dermatology, ophthalmology, and otorhinolaryngology assessments. Cardiac involvement is the main prognostic factor, with cardiovascular death being the leading cause of mortality. Manifestations include unexplained ventricular hypertrophy (which must be differentiated from the more common sarcomeric hypertrophic cardiomyopathy), valvular diseases, angina pectoris due to coronary microcirculation dysfunction, conduction abnormalities (which may require permanent pacemaker implantation), and supraventricular and ventricular tachyarrhythmias. Cardiological evaluation is recommended annually or earlier if clinically indicated, including systemic blood pressure assessment, ECG, echocardiography, and arrhythmia detection via 24-hour Holter ECG monitoring (or extended monitoring [e.g., loop recorder] when deemed appropriate). In recent years, cardiac magnetic resonance imaging (CMR) has become a key investigation not only for diagnosing the disease but also for its follow-up and for evaluating the response to therapy. CMR allows for accurate assessment of cardiac chamber volumes and function and enables tissue characterization using gadolinium-based contrast agents and advanced T1 and T2 mapping techniques. Endomyocardial biopsy is now reserved for patients with genetic variants of uncertain significance (VUS), high residual enzymatic activity (>10%), and/or low lyso-Gb3 levels to confirm or exclude AFD as the cause of left ventricular hypertrophy. 2. Study Background AFD is a rare disease, and the estimated prevalence of the classic forms was previously reported to range between 1:40,000 and 1:117,000. However, these data likely represent an underestimation, as the manifestations are nonspecific, and AFD is often not considered among diagnostic hypotheses, leading to misdiagnosis or delayed diagnosis. Supporting this, recent genetic newborn screening programs not based on symptom development suggest that AFD may be far more common than previously suspected. Although the last decade has seen increasing understanding of the disease's pathophysiological mechanisms, natural history, and the efficacy and limitations of current therapeutic options, many unanswered questions remain. This highlights the need to create an Italian cardiological registry for Anderson-Fabry Disease to bring together various centers located in different regions nationwide to collect the largest possible number of patients. 3. Study Objectives - Evaluate the clinical profile, prevalence, and incidence of the disease (relative to the general population), as well as the family and natural history of AFD patients, particularly the incidence of morbidity/mortality during follow-up. - Identify clinical and instrumental predictors of cardiovascular morbidity and mortality to improve risk stratification and personalize the most appropriate management program for each patient. - Assess the correlation between genetic findings, phenotype, and prognosis, with particular emphasis on differences in cardiac involvement between classic and late-onset variants with cardiac involvement. - Investigate serological/tissue markers and instrumental indicators of early organ damage. 4. Study Plan 4.1 Study Population All patients affected by Anderson-Fabry Disease (AFD), diagnosed according to current international guidelines, will be included in the study upon obtaining informed consent. Based on the estimated prevalence of the disease, the study plans to enroll approximately 800 patients over 10 years. Inclusion Criteria: - Patients diagnosed with Anderson-Fabry Disease. - Age ≥ 2 years at the time of diagnosis. - Informed consent obtained from the patient or their parent/legal guardian. Exclusion Criteria: - None. 4.2 Study Design The study is an Italian multicenter, observational, retrospective, and prospective, non-pharmacological study. Participation will be proposed consecutively to all patients with AFD attending the participating centers, both as outpatients and inpatients. Structured data collection for objective evaluation will occur through a dedicated electronic archive, gathering data from the observation period between January 1, 1981, and December 31, 2031. This electronic archive may be used to obtain or confirm new scientific evidence regarding AFD, particularly focusing on diagnosis, prognosis, and therapy. Data entry into the electronic archive will be based on the review of medical records (outpatient or inpatient), collecting information about demographics, past and recent medical history, family history, genetic investigations, instrumental assessments, signs and symptoms of the disease, and therapy. Data Collection Modes: - Prospective Phase: Patients will be enrolled during hospitalization or at the first outpatient visit after obtaining free and informed consent. Patients will subsequently undergo clinical evaluations, instrumental investigations, and therapeutic interventions as per clinical necessity and standard care practices. A minimum follow-up duration is not required; even a single evaluation suffices for inclusion in the archive. - Retrospective Phase: Data from patients will be retrospectively collected starting from January 1, 1981. In this phase, no predefined observation period is required. If the patient is no longer being followed, a substitute declaration of consent for retrospective observational studies will be used to utilize clinical/instrumental data excluding genetic data. In all cases where it is possible to provide adequate information, particularly when patients return to care centers for health services or follow-up visits, their consent for data processing must be obtained. 4.3 Discontinuation of Participation Patients may choose to discontinue their participation in the study at any time. 4.4 Visits and Assessments Specialist visits, laboratory tests, genetic analyses, and instrumental evaluations to which patients are or will be subjected fall within the normal care pathway, in line with the standard of care. The data collected will derive from initial and follow-up visits or hospitalizations that are part of standard clinical practice. 5. Data Management and Statistical Analysis 5.1 Data Collection Methods Systematic data collection will occur through the creation of a dedicated electronic archive, collecting data for the observation period between January 1, 1981, and December 31, 2031. Clinical data required by the protocol will be pseudonymized and entered by designated staff into an electronic Case Report Form (eCRF) managed via the REDCap platform. The eCRF in REDCap will be developed and managed following the procedure outlined in the "Operational Instruction for the Management and Use of the REDCap Platform" (IOA119). The Principal Investigator must specify the personnel delegated for data management and their respective roles in the study in the Delegation Log. Collected data will be derived from standard care medical records, with no study-specific assessments performed. 5.2 Statistical Methods The collected data will include demographics (age, gender), medical history, instrumental data (ECG, echocardiography, cardiac MRI, stress tests, 24-hour Holter ECG, biopsies), laboratory data (CBC, platelets, renal and liver function, BNP, troponin, serum electrolytes, urinalysis, etc.), genetic investigation findings, and follow-up data. The results of the analysis will be processed statistically in anonymous form to derive the study objectives. Data will be presented using descriptive statistics: - Qualitative parameters will be expressed as numbers or percentages and analyzed using Chi-square or Fisher's exact test. - Quantitative parameters will be expressed as mean and standard deviation or as median and interquartile range, with comparisons between patients performed using parametric tests (ANOVA, Student's t-test) or non-parametric tests (Kruskal-Wallis and Mann-Whitney U tests). A p-value ≤ 0.05 will be considered statistically significant. Statistical analyses will be conducted using Stata/SE v.14.2 for Windows. 6. Administrative Procedures Good Clinical Practice Guidelines This study will be conducted in compliance with Good Clinical Practice (GCP) guidelines [ICH Harmonized Tripartite Guidelines for GCP 1996 Directive 91/507/EEC; D.M. 15.7.1997], the Declaration of Helsinki, and national regulations governing clinical research. By signing the protocol, the investigator agrees to adhere to the procedures and instructions contained therein and to conduct the study according to GCP, the Declaration of Helsinki, and national regulations on clinical trials. Protocol Amendments or Study Modifications Any protocol modifications will be implemented as formal amendments. No protocol modifications are allowed during the study period. Any unforeseen changes in study conduct will be documented in the "Clinical Study Report." Ethical Committee Approval The study protocol, any amendments, informed consent forms, and patient information must be approved by the Ethics Committee. For amendments, the Investigator may immediately implement changes to ensure patient safety and must notify the Ethics Committee within 10 working days. Consent Management Patients will be enrolled during hospitalization or outpatient visits, and each participant must sign an informed consent form. - For the prospective phase, consent will be obtained during the standard diagnostic process. - For the retrospective phase, concerning previously collected data, informed consent will be sought during follow-up visits. For deceased or unreachable patients, data will be processed without consent based on General Authorization No. 146/2019 from the Privacy Authority, excluding genetic data. Documentation Archive. The Investigator is responsible for archiving and storing essential study documents before, during, and after the study in compliance with applicable regulations and GCP. Data in the CRF will be strictly anonymous, and subjects will be identified only by a number and initials. Publication of Results Data publication will occur after processing during the data collection period or after the final update of the archive. Costs No additional costs are foreseen for conducting this study. Clinical evaluations and instrumental examinations are routinely performed in these patients as part of standard clinical practice.
Phase
N/ASpan
518 weeksSponsor
IRCCS Azienda Ospedaliero-Universitaria di BolognaReggio Emilia
Recruiting