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/NCT05968456</url>
    </required_header>
    <id_info>
      <org_study_id>CAfCA-3366</org_study_id>
      <nct_id>NCT05968456</nct_id>
    </id_info>
    <brief_title>Complexity and Frailty in Cardiothoracic and Vascular Anesthesia (CAfCA). Prospective Multicentric Observational Study</brief_title>
    <acronym>CAfCA</acronym>
    <official_title>Complexity and Frailty in Cardiothoracic and Vascular Anesthesia (CAfCA). Prospective Multicentric Observational Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Istituto Clinico Humanitas</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Istituto Clinico Humanitas</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>
        Frailty is a multidimensional syndrome characterized by a decline in physiological&#xD;
        homeostatic reserve, which translates into an increased susceptibility to adverse events and&#xD;
        unfavorable outcomes following even small exposures to physical, physiological or&#xD;
        psychosocial stress.&#xD;
  &#xD;
        In the European population up to 69 years, the prevalence is generally 6,5%, beyond 85 years&#xD;
        of age it exceeds 50% and reaches 65% in the over-ninety population. The prevalence of&#xD;
        frailty in the surgical population varies, depending on the studies, from 10 to 40%. Frailty&#xD;
        and its severity grade represent themselves noticeably as strong predictors of adverse&#xD;
        postoperative outcomes. The strongest evidence of association is recorded between frailty and&#xD;
        mortality at 30 days.&#xD;
  &#xD;
        The purpose of this study is to describe the characteristics of patients undergoing&#xD;
        anesthesia for cardiothoracic and vascular surgery, with a specific focus on frailty elements&#xD;
        and associated comorbidities that necessitate surgery.&#xD;
  &#xD;
        This data analysis will provide valuable insights into the interaction between frailty,&#xD;
        multimorbidity, and the perioperative pathway of patients undergoing cardiothoracic and&#xD;
        vascular anesthesia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The Western population is going through a rapid process of aging, which is of major relevance&#xD;
        for perioperative medicine because it is associated with an increase of approximately 2,5&#xD;
        times in postoperative morbidity and mortality. Despite the clear association between&#xD;
        advanced age and adverse outcomes, there is a significant variability of outcomes in older&#xD;
        patients which is not explainable solely based on the differences in age and comorbidities.&#xD;
        In this regard, frailty seems to play a key role to explain such variability. Frailty is a&#xD;
        multidimensional syndrome characterized by a decline in physiological homeostatic reserve,&#xD;
        which translates into an increased susceptibility to adverse events and unfavorable outcomes&#xD;
        following even small exposures to physical, physiological or psychosocial stress. However,&#xD;
        frailty has not to be considered exclusively in a geriatric context. Several studies&#xD;
        conducted in intensive care and perioperative settings have observed a not negligible&#xD;
        prevalence of frailty also in age groups below 65 years.&#xD;
  &#xD;
        In the European population up to 69 years, the prevalence is generally 6,5%, beyond 85 years&#xD;
        of age it exceeds 50% and reaches 65% in the over-ninety population. The prevalence of&#xD;
        frailty in the surgical population varies, depending on the studies, from 10 to 40%. Such&#xD;
        variability is determined by several factors: the tools and thresholds used to define&#xD;
        frailty, the type of surgery, the type of procedure within the same surgical specialty and&#xD;
        the setting of surgery. In cardiac surgery, prevalences oscillating between 10 and 50% have&#xD;
        been reported. In vascular surgery, the prevalence of frailty is on average high oscillating&#xD;
        between 20 and 60%, while in the field of thoracic surgery data of prevalence stands around&#xD;
        12 and 50%.&#xD;
  &#xD;
        Frailty and its severity grade represent themselves noticeably as strong predictors of&#xD;
        adverse postoperative outcomes. The strongest evidence of association is recorded between&#xD;
        frailty and mortality at 30 days (Odds Ration variable between 1.4 and 8.33).&#xD;
  &#xD;
        In the physio-pathological processes that link frailty to adverse postoperative outcomes,&#xD;
        there are certainly modifiable factors. Several data in the literature demonstrate this&#xD;
        correlation, including the evidence that patients diagnosed with frailty, if subjected to&#xD;
        major elective surgery in centers with low volumes of fragile patients, have lower rates of&#xD;
        survival at 30 days and a higher incidence of mortality correlated to postoperative&#xD;
        complications, other conditions being equal.&#xD;
  &#xD;
        From what has been outlined, it is easy to understand how a better knowledge of frailty and&#xD;
        its prevalence can be useful for health systems that have to be more and more structured with&#xD;
        the availability of clinical and organizational resources appropriate for the increasing&#xD;
        complexity and frailty of patients.&#xD;
  &#xD;
        The purpose of this study is to describe the characteristics of patients undergoing&#xD;
        anesthesia for cardiothoracic and vascular surgery, with a specific focus on frailty elements&#xD;
        and associated comorbidities that necessitate surgery.&#xD;
  &#xD;
        This data analysis will provide valuable insights into the interaction between frailty,&#xD;
        multimorbidity, and the perioperative pathway of patients. Additionally, it will facilitate&#xD;
        the development of a comprehensive description of clinical and organizational resources and&#xD;
        their utilization in managing this specific category of patients.&#xD;
  &#xD;
        This study will lay the foundations for further, more specific studies in this field and will&#xD;
        provide useful information to build more suitable anesthesiologic clinical care pathways for&#xD;
        the increasing demands of fragile and complex patients.&#xD;
  &#xD;
        STUDY DESIGN&#xD;
  &#xD;
        The study will be prospective, multicentric observational at the national level.&#xD;
  &#xD;
        Data collection will not modify anesthetic treatments for patients included in the study or&#xD;
        their treatment pathways. Therefore, according to current legislation, a conclusion of ad hoc&#xD;
        insurance policies is not necessary.&#xD;
  &#xD;
        Anthropometric, functional and procedural data will be collected during the pre-, intra- and&#xD;
        post-operative period.&#xD;
  &#xD;
        The period of observation for each enrolled subject starts with the first pre-operative&#xD;
        anesthesiology assessment and ends 30 days after surgical intervention. Data relative to&#xD;
        preoperative condition, surgical preparation and intra- and post-operative information of the&#xD;
        subject will be collected.&#xD;
  &#xD;
        Data collection will be constituted by a common part including all patients (CAfCA core) and&#xD;
        specific parts related to the fields of cardiac, thoracic and vascular surgery aimed to&#xD;
        specifically characterize these subgroups of patients.&#xD;
  &#xD;
        SAMPLE SIZE&#xD;
  &#xD;
        This research is a prospective pilot study aiming at studying patients subjected to&#xD;
        cardiac-thoracic-vascular surgery. In this field, very heterogeneous data has been reported&#xD;
        in terms of frailty prevalence, as mentioned in the introduction, which varies between 20%&#xD;
        and 60% according to which study is considered.&#xD;
  &#xD;
        Considering a conservative estimation of the frailty prevalence of 50%, a margin of error and&#xD;
        a population of 380 patients is sufficient to estimate the prevalence of frailty in the&#xD;
        cardiac-thoracic-vascular population with a 95% confidence interval. This number is increased&#xD;
        by 5% for a total of 400 patients to take account of missing data and drop-out. To reliably&#xD;
        estimate the prevalence of frailty not only in the general cardiac-thoracic-vascular&#xD;
        population, but also - as the secondary outcome - in each of the 3 subpopulations, meaning&#xD;
        the prevalence of frailty in cardiac, thoracic and vascular surgery, a sample of 500 patients&#xD;
        will allow answering both to the primary outcome of frailty prevalence in the general&#xD;
        population and to the secondary outcome of prevalence in the 3 subpopulations. For this&#xD;
        purpose, it is supposed that every subgroup will contribute with 1/3 of the total enrolled&#xD;
        patients (i.e. 166 patients) and, keeping a conservative estimate of the prevalence of 50%,&#xD;
        in this case, the sample is sufficient to estimate frailty prevalence with a 7.5% margin of&#xD;
        error in each of the 3 subpopulations, with a confidence interval of 95%.&#xD;
  &#xD;
        Considering the observational nature of the study, the protocol allows for the possibility of&#xD;
        recruiting a larger number of patients if the participating centers are willing to do so. By&#xD;
        increasing the sample size, the study can achieve a higher level of precision in estimating&#xD;
        the prevalence of frailty within the investigated subpopulations.&#xD;
  &#xD;
        CLINICAL MANAGEMENT&#xD;
  &#xD;
        During the preoperative anesthesiologic assessment, every eligible patient will be provided&#xD;
        with a detailed explanation of the study protocol. They will be given the opportunity to&#xD;
        review the study information and, if willing to participate, a signed informed consent will&#xD;
        be obtained. Enrollment can take place during the pre-operative assessment or after the&#xD;
        patient's admission to the hospital.&#xD;
  &#xD;
        It is important to note that participating patients have the right to withdraw from the study&#xD;
        at any time.&#xD;
  &#xD;
        During enrolment, patients will be subjected to tests evaluating pharmacologic therapy&#xD;
        adherence (Morinsky scale - MMAS-8), frailty evaluation test (Clinical Frailty Scale - CFS,&#xD;
        Tilburg Frailty Indicator - TFI, Modified Frailty Index both the 5 and 11 items versions -&#xD;
        mFI-5 and mFI-11) and engagement evaluation tests (Patient Health Engagement - PHE score).&#xD;
  &#xD;
        Furthermore, for each patient, the ASA score, Charlson comorbidity score, MUST score, ACS&#xD;
        NSQIP, physiologic P-POSSUM, Revised Cardiac Risk Index (RCRI), AKI risk index and ARISCAT&#xD;
        score will be registered.&#xD;
  &#xD;
        Other evaluation scores will be employed specifically for the different patient types:&#xD;
  &#xD;
          -  Cardiac surgery patients: EUROSCORE II and FORECST (evaluation of frailty in cardiac&#xD;
             surgery)&#xD;
  &#xD;
          -  Thoracic surgery patients: ThRCRI, Thoracoscore, Eurolung 1 and 2, ECOG performance&#xD;
             status scale&#xD;
  &#xD;
          -  Vascular surgery patients: V-Possum&#xD;
  &#xD;
        The data retrieved through the aforementioned scores will not be utilized to modify the&#xD;
        patients' perioperative pathway unless they are already part of specific protocols&#xD;
        implemented by the participating center. The surgical and anesthesiologic procedures will be&#xD;
        conducted according to the local management protocols, and participation in the study will&#xD;
        not result in any modifications to these procedures.&#xD;
  &#xD;
        The experimenters at each center will be limited to reporting the patients' preoperative&#xD;
        clinical conditions, laboratory and instrumental exams, information regarding the performed&#xD;
        surgery, and any complications that occur during the hospital stay.&#xD;
  &#xD;
        The experimenter will conduct re-evaluations of each patient from the first to the fifth&#xD;
        postoperative day, as well as at the time of hospital discharge, in order to record any&#xD;
        potential medical or surgical complications that may arise. Additionally, a follow-up will be&#xD;
        conducted 30 days after discharge via phone to assess the patient's health status and record&#xD;
        any incidences of complications, re-hospitalization, or mortality.&#xD;
  &#xD;
        Complications will be recorded in a specific manner, utilizing the Clavien-Dindo&#xD;
        classification system. This classification system provides standardized criteria for defining&#xD;
        and grading complications. The definitions of complications will be based on established&#xD;
        guidelines and international consensus documents published in the literature, ensuring&#xD;
        consistency and accuracy in the recording and reporting of complications throughout the&#xD;
        study.&#xD;
  &#xD;
        DATA GATHERING AND ANALYSIS PLAN&#xD;
  &#xD;
        Data will be retrieved in pseudo-anonym form. Data gathering will be made through a&#xD;
        specifically created database, on RedCap platform, which has been made available by the&#xD;
        Italian Society of Anesthesiology and Intensive Care Medicine (Società Italiana di Anestesia&#xD;
        Analgesia Rianimazione e Terapia Intensiva - SIAARTI).&#xD;
  &#xD;
        Analysis Plan No interim analyses are expected. Most of the statistical analysis will be&#xD;
        descriptive. Categorical variables considered will be described in terms of frequency and&#xD;
        percentages, and continuous variables in terms of mean (sd) and median (IQR) as appropriate.&#xD;
        The primary objective will be described in terms of prevalence with 95% of the expected&#xD;
        confidence interval.&#xD;
  &#xD;
        Univariate comparative analyses will be conducted through Chi-Square test and Mann-Whitney&#xD;
        U-test as appropriate, considering a significance level of 0.05 in the general population and&#xD;
        stratifying the 3 populations. Missing data will be analyzed and handled if necessary, with&#xD;
        multiple-imputation or analog techniques.&#xD;
  &#xD;
        The correlation between frailty scores will be investigated through Bland-Altman analysis and&#xD;
        correlation coefficient.&#xD;
  &#xD;
        A multivariate correlation analysis will be conducted to explore associations between&#xD;
        preoperative factors, pre-operative risk scores, frailty and outcomes.&#xD;
  &#xD;
        The possibility to perform further analyses non specified in the protocol but suggested by&#xD;
        the above-mentioned planned analyses is admitted (particularly in the&#xD;
        cardiac-thoracic-vascular filed of the three subgroups of patients).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">April 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Frailty Prevalence</measure>
      <time_frame>at preoperative evaluation visit</time_frame>
      <description>Determine the prevalence of frailty in the sample using the Clinical Frailty Score, in the three clinical areas: cardiac, thoracic, and vascular surgery</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Frailty Prevalence comparison</measure>
      <time_frame>at preoperative evaluation visit</time_frame>
      <description>Frailty prevalence comparison among the three clinical areas: cardiac, thoracic, and vascular surgery</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Frailty assessment instruments comparison</measure>
      <time_frame>at preoperative evaluation visit</time_frame>
      <description>Agreement between different frailty instruments</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Multimorbidity description</measure>
      <time_frame>at preoperative evaluation visit</time_frame>
      <description>Describe the multimorbidity profile of the included patients.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>In-hospital complications</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Incidence of in-hospital complications</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Unplanned ICU admission</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Unplanned ICU admissions rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of hospital stay</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Length of hospital stay (days)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>In-hospital mortality</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>In-hospital mortality rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>30-day mortality</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Mortality rate at 30 days after intervention</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between different frailty risk scores and clinical outcomes</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Association between different frailty risk scores and clinical outcomes (complications, length of stay, mortality)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between perioperative risk scores and frailty scores</measure>
      <time_frame>at preoperative evaluation visit</time_frame>
      <description>Correlation between perioperative risk scores and frailty scores</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of the perioperative clinical pathway</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Describe the perioperative clinical care pathway followed by the enrolled subjects</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Description of the anesthesiologic techniques adopted</measure>
      <time_frame>up to 30 days after operation</time_frame>
      <description>Provide details on the anesthesiologic techniques utilized and the level of invasiveness of hemodynamic monitoring employed.</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">500</enrollment>
    <condition>Frailty</condition>
    <condition>Anesthesia</condition>
    <condition>Thoracic Surgery</condition>
    <condition>Cardiothoracic Surgery</condition>
    <condition>Vascular Surgery</condition>
    <condition>Comorbidities and Coexisting Conditions</condition>
    <arm_group>
      <arm_group_label>Thoracic surgery</arm_group_label>
      <description>Patient undergoing thoracic surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cardiac surgery</arm_group_label>
      <description>Patient undergoing cardiac surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Vascular surgery</arm_group_label>
      <description>Patient undergoing vascular surgery</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Data collection</intervention_name>
      <description>Observational study in patients undergoing thoracic, cardiac and vascular surgery.</description>
      <arm_group_label>Cardiac surgery</arm_group_label>
      <arm_group_label>Thoracic surgery</arm_group_label>
      <arm_group_label>Vascular surgery</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients subjected to anesthesia for elective cardiac-thoracic-vascular surgery&#xD;
          consecutively recruited during a period of 1 month designated by each partecipating center&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients scheduled for elective cardiac, thoracic or vascular surgery&#xD;
  &#xD;
            -  Patients aged 18 or older&#xD;
  &#xD;
            -  Patients who have provided informed consent to participate in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients subjected to surgery in urgency and emergency settings&#xD;
  &#xD;
            -  Procedures in one-day surgery settings&#xD;
  &#xD;
            -  Procedures without the involvement of anesthesiologists&#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_official>
      <last_name>Federico Piccioni, Dr</last_name>
      <role>Principal Investigator</role>
      <affiliation>IRCCS Humanitas Research Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Federico Piccioni, Dr</last_name>
      <phone>0282244151</phone>
      <email>federico.piccioni@humanitas.it</email>
    </overall_contact>
    <reference>
      <citation>Fowler AJ, Abbott TEF, Prowle J, Pearse RM. Age of patients undergoing surgery. Br J Surg. 2019 Jul;106(8):1012-1018. doi: 10.1002/bjs.11148. Epub 2019 May 22.</citation>
      <PMID>31115918</PMID>
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    <reference>
      <citation>Hamel MB, Henderson WG, Khuri SF, Daley J. Surgical outcomes for patients aged 80 and older: morbidity and mortality from major noncardiac surgery. J Am Geriatr Soc. 2005 Mar;53(3):424-9. doi: 10.1111/j.1532-5415.2005.53159.x.</citation>
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      <citation>Turrentine FE, Wang H, Simpson VB, Jones RS. Surgical risk factors, morbidity, and mortality in elderly patients. J Am Coll Surg. 2006 Dec;203(6):865-77. doi: 10.1016/j.jamcollsurg.2006.08.026.</citation>
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      <citation>Oresanya LB, Lyons WL, Finlayson E. Preoperative assessment of the older patient: a narrative review. JAMA. 2014 May;311(20):2110-20. doi: 10.1001/jama.2014.4573.</citation>
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    <reference>
      <citation>McIsaac DI, MacDonald DB, Aucoin SD. Frailty for Perioperative Clinicians: A Narrative Review. Anesth Analg. 2020 Jun;130(6):1450-1460. doi: 10.1213/ANE.0000000000004602.</citation>
      <PMID>32384334</PMID>
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    <reference>
      <citation>Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004 Mar;59(3):255-63. doi: 10.1093/gerona/59.3.m255.</citation>
      <PMID>15031310</PMID>
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      <citation>Koh LY, Hwang NC. Frailty in Cardiac Surgery. J Cardiothorac Vasc Anesth. 2019 Feb;33(2):521-531. doi: 10.1053/j.jvca.2018.02.032. Epub 2018 Feb 22. No abstract available.</citation>
      <PMID>29580797</PMID>
    </reference>
    <reference>
      <citation>Gale CR, Cooper C, Sayer AA. Prevalence of frailty and disability: findings from the English Longitudinal Study of Ageing. Age Ageing. 2015 Jan;44(1):162-5. doi: 10.1093/ageing/afu148. Epub 2014 Oct 12.</citation>
      <PMID>25313241</PMID>
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    <reference>
      <citation>McIsaac DI, Wijeysundera DN, Huang A, Bryson GL, van Walraven C. Association of the Hospital Volume of Frail Surgical Patients Cared for with Outcomes after Elective, Major Noncardiac Surgery: A Retrospective Population-based Cohort Study. Anesthesiology. 2017 Apr;126(4):602-613. doi: 10.1097/ALN.0000000000001536.</citation>
      <PMID>28157134</PMID>
    </reference>
    <reference>
      <citation>Lee JA, Yanagawa B, An KR, Arora RC, Verma S, Friedrich JO; Canadian Cardiovascular Surgery Meta-Analysis Working Group. Frailty and pre-frailty in cardiac surgery: a systematic review and meta-analysis of 66,448 patients. J Cardiothorac Surg. 2021 Jun 25;16(1):184. doi: 10.1186/s13019-021-01541-8.</citation>
      <PMID>34172059</PMID>
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      <citation>Sivaharan A, Boylan L, Witham MD, Nandhra S; Northern Vascular Centre. Sarcopenia in Patients Undergoing Lower Limb Bypass Surgery is Associated with Higher Mortality and Major Amputation Rates. Ann Vasc Surg. 2021 Aug;75:227-236. doi: 10.1016/j.avsg.2021.02.022. Epub 2021 Apr 2.</citation>
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      <citation>Tsiouris A, Hammoud ZT, Velanovich V, Hodari A, Borgi J, Rubinfeld I. A modified frailty index to assess morbidity and mortality after lobectomy. J Surg Res. 2013 Jul;183(1):40-6. doi: 10.1016/j.jss.2012.11.059. Epub 2012 Dec 21.</citation>
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    <reference>
      <citation>Beckert AK, Huisingh-Scheetz M, Thompson K, Celauro AD, Williams J, Pachwicewicz P, Ferguson MK. Screening for Frailty in Thoracic Surgical Patients. Ann Thorac Surg. 2017 Mar;103(3):956-961. doi: 10.1016/j.athoracsur.2016.08.078. Epub 2016 Oct 6.</citation>
      <PMID>27720368</PMID>
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    <reference>
      <citation>Handforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, Young J. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol. 2015 Jun;26(6):1091-1101. doi: 10.1093/annonc/mdu540. Epub 2014 Nov 17.</citation>
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    <reference>
      <citation>Lin HS, Watts JN, Peel NM, Hubbard RE. Frailty and post-operative outcomes in older surgical patients: a systematic review. BMC Geriatr. 2016 Aug 31;16(1):157. doi: 10.1186/s12877-016-0329-8.</citation>
      <PMID>27580947</PMID>
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    <reference>
      <citation>Stortecky S, Schoenenberger AW, Moser A, Kalesan B, Juni P, Carrel T, Bischoff S, Schoenenberger CM, Stuck AE, Windecker S, Wenaweser P. Evaluation of multidimensional geriatric assessment as a predictor of mortality and cardiovascular events after transcatheter aortic valve implantation. JACC Cardiovasc Interv. 2012 May;5(5):489-496. doi: 10.1016/j.jcin.2012.02.012.</citation>
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    <reference>
      <citation>Velanovich V, Antoine H, Swartz A, Peters D, Rubinfeld I. Accumulating deficits model of frailty and postoperative mortality and morbidity: its application to a national database. J Surg Res. 2013 Jul;183(1):104-10. doi: 10.1016/j.jss.2013.01.021. Epub 2013 Feb 1.</citation>
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    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Istituto Clinico Humanitas</investigator_affiliation>
      <investigator_full_name>Federico Piccioni</investigator_full_name>
      <investigator_title>Head of Anesthesia Section 1</investigator_title>
    </responsible_party>
    <keyword>Frailty</keyword>
    <keyword>Thoracic surgery</keyword>
    <keyword>Cardiac Surgery</keyword>
    <keyword>Vascular Surgery</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Frailty</mesh_term>
    </condition_browse>
    <!-- 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/NCT05968456
  org study id: CAfCA-3366
  nct id: NCT05968456
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  Frailty is a multidimensional syndrome characterized by a decline in physiological
        homeostatic reserve, which translates into an increased susceptibility to adverse events and
        unfavorable outcomes following even small exposures to physical, physiological or
        psychosocial stress.
  
        In the European population up to 69 years, the prevalence is generally 6,5%, beyond 85 years
        of age it exceeds 50% and reaches 65% in the over-ninety population. The prevalence of
        frailty in the surgical population varies, depending on the studies, from 10 to 40%. Frailty
        and its severity grade represent themselves noticeably as strong predictors of adverse
        postoperative outcomes. The strongest evidence of association is recorded between frailty and
        mortality at 30 days.
  
        The purpose of this study is to describe the characteristics of patients undergoing
        anesthesia for cardiothoracic and vascular surgery, with a specific focus on frailty elements
        and associated comorbidities that necessitate surgery.
  
        This data analysis will provide valuable insights into the interaction between frailty,
        multimorbidity, and the perioperative pathway of patients undergoing cardiothoracic and
        vascular anesthesia.
  The Western population is going through a rapid process of aging, which is of major relevance
        for perioperative medicine because it is associated with an increase of approximately 2,5
        times in postoperative morbidity and mortality. Despite the clear association between
        advanced age and adverse outcomes, there is a significant variability of outcomes in older
        patients which is not explainable solely based on the differences in age and comorbidities.
        In this regard, frailty seems to play a key role to explain such variability. Frailty is a
        multidimensional syndrome characterized by a decline in physiological homeostatic reserve,
        which translates into an increased susceptibility to adverse events and unfavorable outcomes
        following even small exposures to physical, physiological or psychosocial stress. However,
        frailty has not to be considered exclusively in a geriatric context. Several studies
        conducted in intensive care and perioperative settings have observed a not negligible
        prevalence of frailty also in age groups below 65 years.
  
        In the European population up to 69 years, the prevalence is generally 6,5%, beyond 85 years
        of age it exceeds 50% and reaches 65% in the over-ninety population. The prevalence of
        frailty in the surgical population varies, depending on the studies, from 10 to 40%. Such
        variability is determined by several factors: the tools and thresholds used to define
        frailty, the type of surgery, the type of procedure within the same surgical specialty and
        the setting of surgery. In cardiac surgery, prevalences oscillating between 10 and 50% have
        been reported. In vascular surgery, the prevalence of frailty is on average high oscillating
        between 20 and 60%, while in the field of thoracic surgery data of prevalence stands around
        12 and 50%.
  
        Frailty and its severity grade represent themselves noticeably as strong predictors of
        adverse postoperative outcomes. The strongest evidence of association is recorded between
        frailty and mortality at 30 days (Odds Ration variable between 1.4 and 8.33).
  
        In the physio-pathological processes that link frailty to adverse postoperative outcomes,
        there are certainly modifiable factors. Several data in the literature demonstrate this
        correlation, including the evidence that patients diagnosed with frailty, if subjected to
        major elective surgery in centers with low volumes of fragile patients, have lower rates of
        survival at 30 days and a higher incidence of mortality correlated to postoperative
        complications, other conditions being equal.
  
        From what has been outlined, it is easy to understand how a better knowledge of frailty and
        its prevalence can be useful for health systems that have to be more and more structured with
        the availability of clinical and organizational resources appropriate for the increasing
        complexity and frailty of patients.
  
        The purpose of this study is to describe the characteristics of patients undergoing
        anesthesia for cardiothoracic and vascular surgery, with a specific focus on frailty elements
        and associated comorbidities that necessitate surgery.
  
        This data analysis will provide valuable insights into the interaction between frailty,
        multimorbidity, and the perioperative pathway of patients. Additionally, it will facilitate
        the development of a comprehensive description of clinical and organizational resources and
        their utilization in managing this specific category of patients.
  
        This study will lay the foundations for further, more specific studies in this field and will
        provide useful information to build more suitable anesthesiologic clinical care pathways for
        the increasing demands of fragile and complex patients.
  
        STUDY DESIGN
  
        The study will be prospective, multicentric observational at the national level.
  
        Data collection will not modify anesthetic treatments for patients included in the study or
        their treatment pathways. Therefore, according to current legislation, a conclusion of ad hoc
        insurance policies is not necessary.
  
        Anthropometric, functional and procedural data will be collected during the pre-, intra- and
        post-operative period.
  
        The period of observation for each enrolled subject starts with the first pre-operative
        anesthesiology assessment and ends 30 days after surgical intervention. Data relative to
        preoperative condition, surgical preparation and intra- and post-operative information of the
        subject will be collected.
  
        Data collection will be constituted by a common part including all patients (CAfCA core) and
        specific parts related to the fields of cardiac, thoracic and vascular surgery aimed to
        specifically characterize these subgroups of patients.
  
        SAMPLE SIZE
  
        This research is a prospective pilot study aiming at studying patients subjected to
        cardiac-thoracic-vascular surgery. In this field, very heterogeneous data has been reported
        in terms of frailty prevalence, as mentioned in the introduction, which varies between 20%
        and 60% according to which study is considered.
  
        Considering a conservative estimation of the frailty prevalence of 50%, a margin of error and
        a population of 380 patients is sufficient to estimate the prevalence of frailty in the
        cardiac-thoracic-vascular population with a 95% confidence interval. This number is increased
        by 5% for a total of 400 patients to take account of missing data and drop-out. To reliably
        estimate the prevalence of frailty not only in the general cardiac-thoracic-vascular
        population, but also - as the secondary outcome - in each of the 3 subpopulations, meaning
        the prevalence of frailty in cardiac, thoracic and vascular surgery, a sample of 500 patients
        will allow answering both to the primary outcome of frailty prevalence in the general
        population and to the secondary outcome of prevalence in the 3 subpopulations. For this
        purpose, it is supposed that every subgroup will contribute with 1/3 of the total enrolled
        patients (i.e. 166 patients) and, keeping a conservative estimate of the prevalence of 50%,
        in this case, the sample is sufficient to estimate frailty prevalence with a 7.5% margin of
        error in each of the 3 subpopulations, with a confidence interval of 95%.
  
        Considering the observational nature of the study, the protocol allows for the possibility of
        recruiting a larger number of patients if the participating centers are willing to do so. By
        increasing the sample size, the study can achieve a higher level of precision in estimating
        the prevalence of frailty within the investigated subpopulations.
  
        CLINICAL MANAGEMENT
  
        During the preoperative anesthesiologic assessment, every eligible patient will be provided
        with a detailed explanation of the study protocol. They will be given the opportunity to
        review the study information and, if willing to participate, a signed informed consent will
        be obtained. Enrollment can take place during the pre-operative assessment or after the
        patient's admission to the hospital.
  
        It is important to note that participating patients have the right to withdraw from the study
        at any time.
  
        During enrolment, patients will be subjected to tests evaluating pharmacologic therapy
        adherence (Morinsky scale - MMAS-8), frailty evaluation test (Clinical Frailty Scale - CFS,
        Tilburg Frailty Indicator - TFI, Modified Frailty Index both the 5 and 11 items versions -
        mFI-5 and mFI-11) and engagement evaluation tests (Patient Health Engagement - PHE score).
  
        Furthermore, for each patient, the ASA score, Charlson comorbidity score, MUST score, ACS
        NSQIP, physiologic P-POSSUM, Revised Cardiac Risk Index (RCRI), AKI risk index and ARISCAT
        score will be registered.
  
        Other evaluation scores will be employed specifically for the different patient types:
  
          -  Cardiac surgery patients: EUROSCORE II and FORECST (evaluation of frailty in cardiac
             surgery)
  
          -  Thoracic surgery patients: ThRCRI, Thoracoscore, Eurolung 1 and 2, ECOG performance
             status scale
  
          -  Vascular surgery patients: V-Possum
  
        The data retrieved through the aforementioned scores will not be utilized to modify the
        patients' perioperative pathway unless they are already part of specific protocols
        implemented by the participating center. The surgical and anesthesiologic procedures will be
        conducted according to the local management protocols, and participation in the study will
        not result in any modifications to these procedures.
  
        The experimenters at each center will be limited to reporting the patients' preoperative
        clinical conditions, laboratory and instrumental exams, information regarding the performed
        surgery, and any complications that occur during the hospital stay.
  
        The experimenter will conduct re-evaluations of each patient from the first to the fifth
        postoperative day, as well as at the time of hospital discharge, in order to record any
        potential medical or surgical complications that may arise. Additionally, a follow-up will be
        conducted 30 days after discharge via phone to assess the patient's health status and record
        any incidences of complications, re-hospitalization, or mortality.
  
        Complications will be recorded in a specific manner, utilizing the Clavien-Dindo
        classification system. This classification system provides standardized criteria for defining
        and grading complications. The definitions of complications will be based on established
        guidelines and international consensus documents published in the literature, ensuring
        consistency and accuracy in the recording and reporting of complications throughout the
        study.
  
        DATA GATHERING AND ANALYSIS PLAN
  
        Data will be retrieved in pseudo-anonym form. Data gathering will be made through a
        specifically created database, on RedCap platform, which has been made available by the
        Italian Society of Anesthesiology and Intensive Care Medicine (Società Italiana di Anestesia
        Analgesia Rianimazione e Terapia Intensiva - SIAARTI).
  
        Analysis Plan No interim analyses are expected. Most of the statistical analysis will be
        descriptive. Categorical variables considered will be described in terms of frequency and
        percentages, and continuous variables in terms of mean (sd) and median (IQR) as appropriate.
        The primary objective will be described in terms of prevalence with 95% of the expected
        confidence interval.
  
        Univariate comparative analyses will be conducted through Chi-Square test and Mann-Whitney
        U-test as appropriate, considering a significance level of 0.05 in the general population and
        stratifying the 3 populations. Missing data will be analyzed and handled if necessary, with
        multiple-imputation or analog techniques.
  
        The correlation between frailty scores will be investigated through Bland-Altman analysis and
        correlation coefficient.
  
        A multivariate correlation analysis will be conducted to explore associations between
        preoperative factors, pre-operative risk scores, frailty and outcomes.
  
        The possibility to perform further analyses non specified in the protocol but suggested by
        the above-mentioned planned analyses is admitted (particularly in the
        cardiac-thoracic-vascular filed of the three subgroups of patients).
  observational model: Cohort
  time perspective: Prospective
  measure: Frailty Prevalence
  time frame: at preoperative evaluation visit
  description: Determine the prevalence of frailty in the sample using the Clinical Frailty Score, in the three clinical areas: cardiac, thoracic, and vascular surgery
  measure: Frailty Prevalence comparison
  time frame: at preoperative evaluation visit
  description: Frailty prevalence comparison among the three clinical areas: cardiac, thoracic, and vascular surgery
  measure: Frailty assessment instruments comparison
  time frame: at preoperative evaluation visit
  description: Agreement between different frailty instruments
  measure: Multimorbidity description
  time frame: at preoperative evaluation visit
  description: Describe the multimorbidity profile of the included patients.
  measure: In-hospital complications
  time frame: up to 30 days after operation
  description: Incidence of in-hospital complications
  measure: Unplanned ICU admission
  time frame: up to 30 days after operation
  description: Unplanned ICU admissions rate
  measure: Length of hospital stay
  time frame: up to 30 days after operation
  description: Length of hospital stay (days)
  measure: In-hospital mortality
  time frame: up to 30 days after operation
  description: In-hospital mortality rate
  measure: 30-day mortality
  time frame: up to 30 days after operation
  description: Mortality rate at 30 days after intervention
  measure: Association between different frailty risk scores and clinical outcomes
  time frame: up to 30 days after operation
  description: Association between different frailty risk scores and clinical outcomes (complications, length of stay, mortality)
  measure: Correlation between perioperative risk scores and frailty scores
  time frame: at preoperative evaluation visit
  description: Correlation between perioperative risk scores and frailty scores
  measure: Description of the perioperative clinical pathway
  time frame: up to 30 days after operation
  description: Describe the perioperative clinical care pathway followed by the enrolled subjects
  measure: Description of the anesthesiologic techniques adopted
  time frame: up to 30 days after operation
  description: Provide details on the anesthesiologic techniques utilized and the level of invasiveness of hemodynamic monitoring employed.
  arm group label: Thoracic surgery
  description: Patient undergoing thoracic surgery
  arm group label: Cardiac surgery
  description: Patient undergoing cardiac surgery
  arm group label: Vascular surgery
  description: Patient undergoing vascular surgery
  intervention type: Other
  intervention name: Data collection
  description: Observational study in patients undergoing thoracic, cardiac and vascular surgery.
  arm group label: Cardiac surgery
  arm group label: Thoracic surgery
  arm group label: Vascular surgery
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Federico Piccioni, Dr
  role: Principal Investigator
  affiliation: IRCCS Humanitas Research Hospital
  last name: Federico Piccioni, Dr
  phone: 0282244151
  email: federico.piccioni@humanitas.it
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  PMID: 31115918
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  PMID: 15743284
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  PMID: 17116555
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  PMID: 24867014
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  PMID: 32384334
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  PMID: 15031310
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  PMID: 29580797
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  PMID: 25313241
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  PMID: 28157134
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  PMID: 34172059
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  PMID: 23415494
  responsible party type: Principal Investigator
  investigator affiliation: Istituto Clinico Humanitas
  investigator full name: Federico Piccioni
  investigator title: Head of Anesthesia Section 1
  mesh term: Frailty