xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05977777</url>
    </required_header>
    <id_info>
      <org_study_id>5220</org_study_id>
      <nct_id>NCT05977777</nct_id>
    </id_info>
    <brief_title>Contrast-enhanced Ultrasound and Pancreatic Lesions</brief_title>
    <official_title>Characterization of Pancreatic Lesions Using Dynamic Contrast-enhanced Ultrasound</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The characterization of pancreatic lesions is one of the fundamental steps in the management&#xD;
        of pancreatic neoplastic diseases. In terms of a subjective assessment of vascular&#xD;
        enhancement in the various examination stages, the use of contrast-enhanced ultrasonography&#xD;
        (CEUS) in the study of pancreatic neoplastic disease has been thoroughly investigated.&#xD;
        Technology advancements have enabled the development of software that can perform an&#xD;
        objective study of the parameters of vascular enhancement and their variations during dynamic&#xD;
        CEUS (DCEUS). Currently, the paucity of data regarding the characterization of pancreatic&#xD;
        lesions trough DCEUS limit the definition of its role in pancreatic disease. The main purpose&#xD;
        of this study is to employ the knowledge in this field trough the characterization of focal&#xD;
        pancreatic lesions using DCEUS.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Pancreatic cancer is currently one of the most prevalent malignant neoplasms, characterized&#xD;
        by an increasing prevalence and a high mortality and lethality rate. It is the seventh most&#xD;
        common malignant tumor in the general population, the fourth most deadly in both sexes, with&#xD;
        a 5-year survival rate of approximately 9%. The lack of an early diagnostic tool and the&#xD;
        absence of effective treatments for advanced-stage disease are the major contributors to this&#xD;
        poor prognosis.&#xD;
  &#xD;
        The diagnosis of pancreatic cancer is based on the results of multiple examinations,&#xD;
        including various imaging modalities, until the histological diagnosis is obtained through&#xD;
        biopsy. Transabdominal ultrasound (US) computed tomography (CT), magnetic resonance imaging&#xD;
        (MRI), and endoscopic ultrasound (EUS) are performed to detect and stage pancreas cancer in&#xD;
        resectable, borderline, locally advanced and metastatic. Hence, the differential diagnosis&#xD;
        and characterization of solid pancreatic tumors represent a crucial step in identifying a&#xD;
        suitable therapeutic strategy.&#xD;
  &#xD;
        Transabdominal US is frequently used as a first-line diagnostic tool for patients with&#xD;
        suspected pancreatic diseases. The main limitation of transabdominal US is the low accuracy&#xD;
        in the differential diagnosis between malignant and benign solid lesions, and, considering&#xD;
        malignant lesions, between the different pancreatic tumors (adenocarcinomas, neuroendocrine&#xD;
        tumors, carcinosarcomas, lymphomas) since all these masses appear as hypoechoic formations.&#xD;
  &#xD;
        The introduction of ultrasound contrast agent (UCA) has significantly improved the diagnostic&#xD;
        abilities of conventional ultrasound and contrast enhanced ultrasound (CEUS) has been widely&#xD;
        implemented in clinical practice because of the enormous quantity of information it provides,&#xD;
        along with its low cost, reproducibility, minimal invasiveness, and safety of the UCA. In the&#xD;
        detection of pancreatic cancer, contrast enhanced ultrasound (CEUS) achieve a sensitivity and&#xD;
        specificity of 92% and 76%, respectively. The European Federation for Ultrasound in Medicine&#xD;
        and Biology (EFSUMB) has recently defined the importance of contrast-enhanced ultrasonography&#xD;
        (CEUS) in the diagnosis of pancreatic disease, supporting its use to characterize&#xD;
        B-mode-identified pancreatic solid lesions.&#xD;
  &#xD;
        Despite its numerous advantages, one of the most significant limitations of CEUS is the&#xD;
        subjective evaluation of contrast enhancement related behavior of tissues examined. In recent&#xD;
        years, one of the methods explored to overcome this limitation has been the Dynamic CEUS&#xD;
        (DCEUS) which allow the quantitative analysis of UCA-kinetics in a specific region of&#xD;
        interest (ROI). It consists of measuring the average intensity of a ROI following a bolus&#xD;
        injection of UCA and generating a time-intensity curve (TIC). Then, multiple parameters are&#xD;
        derived from the TIC to quantitatively characterize the different stages of the wash-in and&#xD;
        wash-out phases. These parameters can be divided into three categories: time parameters,&#xD;
        intensity parameters and area under the curve (AUC).&#xD;
  &#xD;
        Very few evidence has been published concerning the use of DCEUS in the characterization of&#xD;
        pancreatic lesions. Kersting et al performed DCEUS in sixty undetermined pancreatic lesions&#xD;
        then histologically characterized as pancreatic ductal adenocarcinoma (PDAC) (n = 45) or&#xD;
        inflammatory lesion in chronic pancreatitis (CP) (n = 15). The grouped analysis of TICs&#xD;
        showed a significant prolonged time to peak and arrival time for PDAC then CP compared with&#xD;
        normal pancreatic tissue. In another study, D'Onofrio et al performed a quantitative&#xD;
        perfusion analysis of ten prospectively enrolled patients with suspected pancreatic ductal&#xD;
        adenocarcinoma (PDAC). The results showed a significant difference in peak of enhancement and&#xD;
        ascending curve between PDAC and normal pancreatic parenchyma, providing an objective&#xD;
        quantification of enhancement for the assessment of pancreatic lesion. These findings suggest&#xD;
        a potential usefulness of DCEUS in characterizing and differentiating focal pancreatic&#xD;
        lesions. However, the amount of data currently available in the published studies is limited.&#xD;
  &#xD;
        The main purpose of this study is to employ the knowledge in this field trough the&#xD;
        characterization of focal pancreatic lesions using DCEUS.&#xD;
  &#xD;
        Materials and methods Fifty patients with a transabdominal US diagnosis of a pancreatic&#xD;
        lesion who receive CEUS and a subsequent biopsy for histologic characterization will be&#xD;
        enrolled in this prospective study. Inclusion criteria are at least 18 years of age, at least&#xD;
        one pancreatic lesion visible in B-mode US and investigated trough CEUS and provide written&#xD;
        consent. Exclusion criteria comprise less than 18 years of age and absence of informed&#xD;
        consent.&#xD;
  &#xD;
        All patients enrolled in this study will be fasting for at least 8 hours before CEUS&#xD;
        examinations. During the B-mode ultrasound, location, size and echogenicity of lesion&#xD;
        detected will be assess. According to CEUS guideline, after the bolus injection of 2.4 ml&#xD;
        sulfur hexafluoride microbubbles (SonoVue/Lumason, Bracco) via peripheral upper limb vein and&#xD;
        followed by a 5-10 ml saline flush, the enhancement features of the lesion during arterial,&#xD;
        portal, and late phases will be recorded and examined. Clinical and laboratoristic data will&#xD;
        be also recorded. After examination, TICs will be obtained and the following quantitative&#xD;
        parameters will be described: peak enhancement, time to peak, area under the curve, mean&#xD;
        transit time and the slope of wash-in curve.&#xD;
  &#xD;
        Statistical analysis This is monocenter, prospective, non-pharmacological trial. Nominal or&#xD;
        ordinal variables will be presented as frequencies and percentages. Mean, standard deviation,&#xD;
        median and 95% confidence intervals will be calculated for continuous variables. Comparison&#xD;
        between means/median will be investigated with Mann-Whitney test. A p value &lt; 0.05 will be&#xD;
        considered statistically significant.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">November 7, 2022</start_date>
    <completion_date type="Anticipated">June 2025</completion_date>
    <primary_completion_date type="Anticipated">November 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>diagnostic agreement between contrast-enhanced ultrasound and histology</measure>
      <time_frame>within 3 months from enrollement</time_frame>
      <description>to quantify peak enhancement intensity in Arbitray Units AU (measured by analysing D-CEUS time-intensity curves) in patients with pancreatic lesions, stratified according to the histologic exam of pancreatic lesions</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Pancreatic Cancer</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients affected by focal pancreatic lesions</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Contrast- enhanced ultrasound</intervention_name>
      <description>Contrast- enahnched ultrasound is performed on target pancreatic lesion</description>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria are:&#xD;
  &#xD;
            -  written informed consent&#xD;
  &#xD;
            -  at least 18 years of age&#xD;
  &#xD;
            -  at least one pancreatic lesion visible in B-mode US and investigated trough CEUS&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
            -  less than 18 years of age&#xD;
  &#xD;
            -  absence of informed consent&#xD;
  &#xD;
            -  knowm allergy to ultrasound contrast agent&#xD;
  &#xD;
            -  hearth failure&#xD;
  &#xD;
            -  pregnancy&#xD;
  &#xD;
            -  lactation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Maria Assunta Zocco</last_name>
      <phone>00393470597805</phone>
      <email>mariaassunta.zocco@policlinicogemelli.it</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fondazione Policlinico Gemelli IRCCS</name>
        <address>
          <city>Roma</city>
          <zip>00168</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>MARIA ASSUNTA ZOCCO, PhD</last_name>
        <phone>00393470597805</phone>
      </contact>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>March 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</investigator_affiliation>
      <investigator_full_name>Zocco Maria Assunta</investigator_full_name>
      <investigator_title>Prof</investigator_title>
    </responsible_party>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05977777
  org study id: 5220
  nct id: NCT05977777
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The characterization of pancreatic lesions is one of the fundamental steps in the management
        of pancreatic neoplastic diseases. In terms of a subjective assessment of vascular
        enhancement in the various examination stages, the use of contrast-enhanced ultrasonography
        (CEUS) in the study of pancreatic neoplastic disease has been thoroughly investigated.
        Technology advancements have enabled the development of software that can perform an
        objective study of the parameters of vascular enhancement and their variations during dynamic
        CEUS (DCEUS). Currently, the paucity of data regarding the characterization of pancreatic
        lesions trough DCEUS limit the definition of its role in pancreatic disease. The main purpose
        of this study is to employ the knowledge in this field trough the characterization of focal
        pancreatic lesions using DCEUS.
  Pancreatic cancer is currently one of the most prevalent malignant neoplasms, characterized
        by an increasing prevalence and a high mortality and lethality rate. It is the seventh most
        common malignant tumor in the general population, the fourth most deadly in both sexes, with
        a 5-year survival rate of approximately 9%. The lack of an early diagnostic tool and the
        absence of effective treatments for advanced-stage disease are the major contributors to this
        poor prognosis.
  
        The diagnosis of pancreatic cancer is based on the results of multiple examinations,
        including various imaging modalities, until the histological diagnosis is obtained through
        biopsy. Transabdominal ultrasound (US) computed tomography (CT), magnetic resonance imaging
        (MRI), and endoscopic ultrasound (EUS) are performed to detect and stage pancreas cancer in
        resectable, borderline, locally advanced and metastatic. Hence, the differential diagnosis
        and characterization of solid pancreatic tumors represent a crucial step in identifying a
        suitable therapeutic strategy.
  
        Transabdominal US is frequently used as a first-line diagnostic tool for patients with
        suspected pancreatic diseases. The main limitation of transabdominal US is the low accuracy
        in the differential diagnosis between malignant and benign solid lesions, and, considering
        malignant lesions, between the different pancreatic tumors (adenocarcinomas, neuroendocrine
        tumors, carcinosarcomas, lymphomas) since all these masses appear as hypoechoic formations.
  
        The introduction of ultrasound contrast agent (UCA) has significantly improved the diagnostic
        abilities of conventional ultrasound and contrast enhanced ultrasound (CEUS) has been widely
        implemented in clinical practice because of the enormous quantity of information it provides,
        along with its low cost, reproducibility, minimal invasiveness, and safety of the UCA. In the
        detection of pancreatic cancer, contrast enhanced ultrasound (CEUS) achieve a sensitivity and
        specificity of 92% and 76%, respectively. The European Federation for Ultrasound in Medicine
        and Biology (EFSUMB) has recently defined the importance of contrast-enhanced ultrasonography
        (CEUS) in the diagnosis of pancreatic disease, supporting its use to characterize
        B-mode-identified pancreatic solid lesions.
  
        Despite its numerous advantages, one of the most significant limitations of CEUS is the
        subjective evaluation of contrast enhancement related behavior of tissues examined. In recent
        years, one of the methods explored to overcome this limitation has been the Dynamic CEUS
        (DCEUS) which allow the quantitative analysis of UCA-kinetics in a specific region of
        interest (ROI). It consists of measuring the average intensity of a ROI following a bolus
        injection of UCA and generating a time-intensity curve (TIC). Then, multiple parameters are
        derived from the TIC to quantitatively characterize the different stages of the wash-in and
        wash-out phases. These parameters can be divided into three categories: time parameters,
        intensity parameters and area under the curve (AUC).
  
        Very few evidence has been published concerning the use of DCEUS in the characterization of
        pancreatic lesions. Kersting et al performed DCEUS in sixty undetermined pancreatic lesions
        then histologically characterized as pancreatic ductal adenocarcinoma (PDAC) (n = 45) or
        inflammatory lesion in chronic pancreatitis (CP) (n = 15). The grouped analysis of TICs
        showed a significant prolonged time to peak and arrival time for PDAC then CP compared with
        normal pancreatic tissue. In another study, D'Onofrio et al performed a quantitative
        perfusion analysis of ten prospectively enrolled patients with suspected pancreatic ductal
        adenocarcinoma (PDAC). The results showed a significant difference in peak of enhancement and
        ascending curve between PDAC and normal pancreatic parenchyma, providing an objective
        quantification of enhancement for the assessment of pancreatic lesion. These findings suggest
        a potential usefulness of DCEUS in characterizing and differentiating focal pancreatic
        lesions. However, the amount of data currently available in the published studies is limited.
  
        The main purpose of this study is to employ the knowledge in this field trough the
        characterization of focal pancreatic lesions using DCEUS.
  
        Materials and methods Fifty patients with a transabdominal US diagnosis of a pancreatic
        lesion who receive CEUS and a subsequent biopsy for histologic characterization will be
        enrolled in this prospective study. Inclusion criteria are at least 18 years of age, at least
        one pancreatic lesion visible in B-mode US and investigated trough CEUS and provide written
        consent. Exclusion criteria comprise less than 18 years of age and absence of informed
        consent.
  
        All patients enrolled in this study will be fasting for at least 8 hours before CEUS
        examinations. During the B-mode ultrasound, location, size and echogenicity of lesion
        detected will be assess. According to CEUS guideline, after the bolus injection of 2.4 ml
        sulfur hexafluoride microbubbles (SonoVue/Lumason, Bracco) via peripheral upper limb vein and
        followed by a 5-10 ml saline flush, the enhancement features of the lesion during arterial,
        portal, and late phases will be recorded and examined. Clinical and laboratoristic data will
        be also recorded. After examination, TICs will be obtained and the following quantitative
        parameters will be described: peak enhancement, time to peak, area under the curve, mean
        transit time and the slope of wash-in curve.
  
        Statistical analysis This is monocenter, prospective, non-pharmacological trial. Nominal or
        ordinal variables will be presented as frequencies and percentages. Mean, standard deviation,
        median and 95% confidence intervals will be calculated for continuous variables. Comparison
        between means/median will be investigated with Mann-Whitney test. A p value < 0.05 will be
        considered statistically significant.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: diagnostic agreement between contrast-enhanced ultrasound and histology
  time frame: within 3 months from enrollement
  description: to quantify peak enhancement intensity in Arbitray Units AU (measured by analysing D-CEUS time-intensity curves) in patients with pancreatic lesions, stratified according to the histologic exam of pancreatic lesions
  arm group label: Patients
  arm group type: Experimental
  description: Patients affected by focal pancreatic lesions
  intervention type: Diagnostic Test
  intervention name: Contrast- enhanced ultrasound
  description: Contrast- enahnched ultrasound is performed on target pancreatic lesion
  arm group label: Patients
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Maria Assunta Zocco
  phone: 00393470597805
  email: mariaassunta.zocco@policlinicogemelli.it
  facility: 
  status: Recruiting
  contact: 
  country: Italy
  responsible party type: Principal Investigator
  investigator affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  investigator full name: Zocco Maria Assunta
  investigator title: Prof