<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/NCT04456036</url>
  </required_header>
  <id_info>
    <org_study_id>NeuroRehabAN_Covid_2020</org_study_id>
    <nct_id>NCT04456036</nct_id>
  </id_info>
  <brief_title>Rehabilitation Needs and Functional Recovery in Covid-19 Acute and Post-acute Care</brief_title>
  <acronym>RECOVER-19</acronym>
  <official_title>Rehabilitation Needs and Functional Recovery in Covid-19 Acute and Post-acute Care: Study of Functional Evolution, Predictors of Activities and Participation Recovery After Severe Covid-19 and Rehabilitation Role</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Università Politecnica delle Marche</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Maria Gabriella Ceravolo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Michela Coccia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lauredana Ercolani</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Elisa Andrenelli</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lucia Pepa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rossella Cima</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Michela Aringolo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Università Politecnica delle Marche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to apply a prospective observational design to describe the&#xD;
      emerging functional impairments of subjects affected by COVID-19 in the acute phase and&#xD;
      monitor their course and impact on activities and participation up to 12 months of onset. The&#xD;
      ultimate goal is to provide a reliable framework to plan rehabilitation delivery to COVID-19&#xD;
      survivors in each phase and foresee health needs in the medium and long term. The secondary&#xD;
      objective of the study is to find predictors of functional recovery, among pre-existing and&#xD;
      emerging individual and contextual factors, with a special focus on the latency of&#xD;
      rehabilitation start after hospital admission.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The disease caused by SARS-CoV-2 infection, COronaVIrus Disease-19 (COVID-19), was first&#xD;
      reported on December 31, 2019. About 20% patients, mostly elderly people, suffered from a&#xD;
      severe form of acute respiratory failure. COVID-19 is a new clinical entity, therefore its&#xD;
      understanding is largely incomplete, in particular as regards medium and long term&#xD;
      consequences both in the clinical and functional domain. An early integration of&#xD;
      rehabilitation care since the acute phase is often required to cope with the functional&#xD;
      sequelae of the severe respiratory syndromes, as well of cardiac and neurological&#xD;
      complications. However, indications, approaches, timing, amount and settings are mainly&#xD;
      unknown due to the lack of epidemiological data regarding the impact of COVID-19 in terms of&#xD;
      body function impairment and activity limitations in the short term and participation&#xD;
      restrictions in the medium and long-term.&#xD;
&#xD;
      The purpose of the study is to apply a prospective observational design to describe the&#xD;
      emerging functional impairments of subjects affected by COVID-19 in the acute phase and&#xD;
      monitor their course and impact on activities and participation up to 12 months of onset. The&#xD;
      ultimate goal is to provide a reliable framework to plan rehabilitation delivery to COVID-19&#xD;
      survivors in each phase and foresee health needs in the medium and long term. The secondary&#xD;
      objective of the study is to find predictors of functional recovery, among pre-existing and&#xD;
      emerging individual and contextual factors, with a special focus on the latency of&#xD;
      rehabilitation start after hospital admission.&#xD;
&#xD;
      The study protocol complements measures of functioning with the indicators used in the&#xD;
      registration form for clinical characterization cases disseminated by the World Health&#xD;
      Organization: in doing so, the authors aim to support the global project of providing Member&#xD;
      States with a standardized approach to collect clinical data.&#xD;
&#xD;
      Study objectives Primary Objective: To describe the emerging functional impairments in&#xD;
      patients hospitalized for SARS-COV-2 infection (COVID-19), and monitor their course and&#xD;
      impact on activities and participation up to 12 months of onset Secondary Objective: To&#xD;
      search for predictive factors of recovery, among the pre-existing and emerging individual and&#xD;
      context-related ones. Particular attention will be paid to the presence and latency of&#xD;
      rehabilitation delivery after hospital admission, describing the functional evolution of&#xD;
      subjects who received rehabilitation since the acute phase, compared to those who did not.&#xD;
&#xD;
      MATERIALS AND METHODS. Study Design. Prospective observational study with 12-month follow-up.&#xD;
      Total study duration: 18 months Population. Adults, male and female, admitted to the&#xD;
      University Hospital &quot;Ospedali Riuniti of Ancona&quot; (UH-ORA) from March 1st, 2020 for the&#xD;
      management of acute COVID-19 infection, able to provide written or oral informed consent. The&#xD;
      only exclusion criterion will be the lack of information concerning clinical data regarding&#xD;
      the management in the acute ward.&#xD;
&#xD;
      Data collection: A paper CRF and an eCRF will be implemented to record patients' data&#xD;
&#xD;
        -  Clinical, laboratory and instrumental data collected in the acute phase will be&#xD;
           retrieved, retrospectively, from patients' clinical records.&#xD;
&#xD;
        -  Data concerning function impairments, activity limitations and participation&#xD;
           restrictions will be collected through direct assessment carried out by the&#xD;
           rehabilitation team at the enrollment, on the first referral of the patient for&#xD;
           counseling (T0) and at hospital discharge (Td) (for those who will receive&#xD;
           rehabilitation in the acute ward), as well as at 3 , 6 and 12 months of COVID-19&#xD;
           diagnosis (T3, T6, T12). Patient reported outcomes will be assessed through&#xD;
           questionnaires and interviews, also delivered by telephone or video-consultation.&#xD;
&#xD;
      The primary endpoint is the change in the overall health status observed at enrolment (T0),&#xD;
      compared to the pre-COVID-19 condition, and its evolution at 3, 6 and 12 months. To this aim,&#xD;
      we will assess:&#xD;
&#xD;
        -  independence in activities of daily living (ADLs), by the modified Rankin scale. The&#xD;
           modified Rankin scale is a rapid and validated measure of global independence in ADL&#xD;
           with a score ranging from 0 (no disability) to 5 (bedridden). To assess changes, the&#xD;
           pre-COVID mod. Rankin scale score, retrospectively ascertained, will be compared to the&#xD;
           scores prospectively collected at enrolment and at 3, 6 and 12 months&#xD;
&#xD;
        -  walking performance, by the Walking Handicap scale (WHS). The Walking Handicap scale is&#xD;
           a quick and validated measure of walking performance, with a score ranging from 1&#xD;
           (Physiological walker: Walks for exercise only either at home or in parallel bars during&#xD;
           physical therapy) to 6 (Community walker: Independent in all home and community&#xD;
           activities. Can accept crowds and uneven terrain. Demonstrates complete independence in&#xD;
           shopping centers). To assess changes, the pre-COVID WHS score, retrospectively&#xD;
           ascertained, will be compared to the scores prospectively collected at 3, 6 and 12&#xD;
           months&#xD;
&#xD;
        -  health-related quality of life perception, by the 36-Item Short Form Survey (SF-36).&#xD;
           SF-36 is a widespread validated scale assessing patient-reported changes in&#xD;
           health-related well-being perception over the last 4 weeks. SF-36 scores will be&#xD;
           collected at 3, 6 and 12 months.&#xD;
&#xD;
      The secondary endpoint is the identification of the predictors of functional recovery at 3, 6&#xD;
      and 12 months, among the pre-existing and emerging individual and context-related factors.&#xD;
&#xD;
      The following explanatory variables will be considered:&#xD;
&#xD;
        -  Pre-existing individual factors: age, gender, blood type, nutritional status,&#xD;
           comorbidity (Modified Cumulative Illness Rating Scale - CIRS), life habits and&#xD;
           pre-existing disability (modified Rankin Scale and Walking Handicap scale in pre-COVID&#xD;
           phase)&#xD;
&#xD;
        -  Emerging individual factors: severity of COVID-19 on admission to the acute ward,&#xD;
           severity of pneumonia during hospitalization (according to Li et al 2020), blood&#xD;
           chemistry (e.g. levels of interleukine, albumin, creatinine, CRP), pulmonary&#xD;
           thromboembolism, neurologic complications, swallow disorders in the acute phase;&#xD;
           severity of body function impairment and activity limitation on enrolment (as measured&#xD;
           by the Trunk control test-TCT, Standing Balance-SB, Functional Ambulation Category-FAC,&#xD;
           modified Barthel index- mBI, Montreal Cognitive Assessment-MoCA)&#xD;
&#xD;
        -  Emerging context-related factors: drug treatment in the acute phase (e.g. ACE&#xD;
           inhibitors, Angiotensin II receptor blockers, Nonsteroidal anti-inflammatories,&#xD;
           Antivirals, heparin), procedures adopted in the ICU (prone positioning, tracheostomy,&#xD;
           support for ventilation, ECMO, Renal replacement therapy or dialysis,&#xD;
           Inotropes/vasopressors), rehabilitation delivery in the acute ward and latency from&#xD;
           hospital admission to rehabilitation start.&#xD;
&#xD;
      Clinical-functional evaluations will be carried out at the following time-points:&#xD;
&#xD;
      T0 = on enrolment Td = discharge from the acute ward (only for subjects who are enrolled&#xD;
      during their stay in the acute ward) T3, T6, T12 = three, six and 12 months after hospital&#xD;
      admission due to COVID-19 infection.&#xD;
&#xD;
      After discharge from hospital, the assessments will be carried out in the outpatient&#xD;
      laboratory; in case of mobility restrictions, questionnaires will be delivered and interviews&#xD;
      will be conducted by telephone or by video consulting.&#xD;
&#xD;
      Sample size and data analysis. Given the nature of the study, a formal calculation of the&#xD;
      sample size was not made. The enrolment of at least 100 subjects is estimated based on&#xD;
      COVID-19 incidence in the catchment population of the UH-ORA.&#xD;
&#xD;
      A descriptive analysis will be conducted on the collected variables using point estimates and&#xD;
      variability measures for quantitative variables or absolute and relative frequencies for&#xD;
      category variables.&#xD;
&#xD;
      A multivariate model will be constructed to extrapolate predictors of poor recovery at 12&#xD;
      months (i.e. Delta T12-T0 on modified Rankin score : &gt;1), by adjusting for potential&#xD;
      confounders. After checking for the normal distribution of quantitative measures, the&#xD;
      analysis of variance (ANOVA) for repeated measures will be applied to analyze the&#xD;
      distribution of functional outcome measures, at 3, 6 and 12 months, among those who received&#xD;
      rehabilitation in the acute phase, respect to those who did not.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>12 Months</target_duration>
  <primary_outcome>
    <measure>Change from pre-COVID-19 condition in ADL independence on the mod. Rankin scale score at the enrolment (T0) assessment, at 3, 6 and 12 months</measure>
    <time_frame>Pre-COVID status, at enrolment and at 3, 6 12-month follow-up</time_frame>
    <description>mod. Rankin scale is a rapid and validated measure of global independence in ADL with a score ranging from 0 (no disability) to 5 (bedridden).&#xD;
Change= pre-COVID mod. Rankin scale score (retrospective data) - mod. Rankin scale score prospectively collected at the enrolment (T0) and at 3, 6 and 12 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from pre-COVID-19 condition in walking performance on the Walking Handicap scale (WHS) at 3, 6 and 12 months</measure>
    <time_frame>Pre-COVID status , and 3, 6 12-month follow-up</time_frame>
    <description>The Walking Handicap scale is a quick and validated measure of walking performance, with a score ranging from 1 (Physiological walker: Walks for exercise only either at home or in parallel bars during physical therapy) to 6 (Community walker: Independent in all home and community activities. Can accept crowds and uneven terrain. Demonstrates complete independence in shopping centers).&#xD;
Change= pre-COVID WHS (retrospective data) - WHS score prospectively collected at 3, 6 and 12 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient-reported health-related well-being perception on the 36-Item Short Form Survey - SF-36 at 3, 6 12 months follow-up</measure>
    <time_frame>3, 6 and 12-month follow-up</time_frame>
    <description>SF-36 is a widespread validated scale assessing patient-reported changes in health-related well-being perception over the last 4 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in global ADL disability on modified Barthel Index (mBI), from the enrolment (T0), at 3, 6 12 months follow-up</measure>
    <time_frame>the enrolment (T0) assesssment and 3, 6 and 12-month follow-up</time_frame>
    <description>The mBI is a validated measure of physical disability widely used to assess individual behavior in activities of daily living for patients with disabling conditions. It measures what patients do in practice. Score assignment can be made without any previous formal training.&#xD;
Change = mBI score at the enrolment (T0) assessment - mBI score at 3, 6 and 12-month follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in walking capacity on Functional Ambulation Category (FAC), from the enrolment (T0) assessment, at 3, 6 12 months follow-up</measure>
    <time_frame>Pre-COVID status, the enrollment (T0) assessment and 3, 6 12-month follow-up</time_frame>
    <description>FAC is a validated measures of gait capacity with a score ranging from 0 (unable to walk) to 5 (able to walk independently in any environment)&#xD;
Change= pre-COVID FAC score (retrospective data) - FAC score prospectively collected at the enrolment (T0) assessment and at 3, 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cognitive abilities on the Montreal Cognitive Assessment (MoCA) from the enrollment (T0) assessment, at 3, 6 12 months follow-up</measure>
    <time_frame>the enrollment (T0) assessment and 3, 6 and 12-month assessment follow-up</time_frame>
    <description>The MoCA is a cognitive screening test designed to assist health professionals in the detection of mild cognitive impairment. It is especially sensitive at detecting dysfunctions in executive strategies.&#xD;
Change = MoCA score at the enrollment (T0) - MoCA score at 3, 6 and 12-month follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in patient-reported pain on Numerical Rating Scale from the enrollment (T0) assessment, at 3, 6 12 months follow-up</measure>
    <time_frame>the enrollment (T0) and 3, 6 and 12-month assessment follow-up</time_frame>
    <description>Pain NRS is a widespread validate assessment tool measuring pain perception with a score ranging from 0 (no pain), to 10 (worst ever pain).&#xD;
Change= NRS score at the enrollment (T0) assessment - NRS score at 3, 6 and 12-month follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in swallow abilities on Dysphagia Outcome Severity Scale (DOSS) from the first functional assessment in acute care, at 3, 6 12 months follow-up</measure>
    <time_frame>the enrollment (T0) assessment and 3, 6 and 12-month assessment follow-up</time_frame>
    <description>DOSS is a simple, easy-to-use, 7-point scale developed to systematically rate the functional severity of dysphagia based on objective assessment, with a score ranging from 1 (severe dysphagia: Non Per oral nutrition) to 7 ( Full per oral nutrition).&#xD;
Change= DOSS score at enrolment (T0) - DOSS score at 3, 6 and 12-month follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in endurance on 6-Minutes Walking Test (6MWT) from the enrolment (T0) assessment, at 3, 6 12 months follow-up</measure>
    <time_frame>the enrolment (T0) and 3, 6 and 12-month assessment follow-up</time_frame>
    <description>6MWT is a validated and synthetic measure of endurance influenced by cardio-respiratory and motor function impairment.&#xD;
Change = 6MWT on enrolment (T0) - 6MWT score at 3, 6 and 12-month follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mood status on Beck Depression Inventory (BDI) from the enrolment (T0) assessment, at 3, 6 and 12 month follow-up</measure>
    <time_frame>enrolment (T0) assessment and 3, 6 and 12-month assessment follow-up</time_frame>
    <description>The BDI is a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression.&#xD;
Change = BDI on enrolment (T0) assessment - BDI score at 3, 6 and 12-month follow-up</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>COVID-19</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Adults, male and female, admitted to the University Hospital &quot;Ospedali Riuniti of Ancona&quot;&#xD;
        (UH-ORA) from March 1st, 2020 for the management of acute COVID-19 infection, able to&#xD;
        provide written or oral informed consent. The only exclusion criterion will be the lack of&#xD;
        information concerning clinical data regarding the management in the acute ward.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt;= 18 years,&#xD;
&#xD;
          -  any gender,&#xD;
&#xD;
          -  COVID-19 diagnosis: positive oro-pharyngeal swab for SARS-COV-2&#xD;
&#xD;
          -  admitted to the University Hospital &quot;Ospedali Riuniti of Ancona&quot; (UH-ORA) from March&#xD;
             1st, 2020 for the management of acute COVID-19,&#xD;
&#xD;
          -  able to provide written or oral informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  the lack of information concerning clinical data regarding the management in the acute&#xD;
             ward.&#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>Maria Gabriella Ceravolo, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Dep. of Experimental and Clinical Medicine - University Politecnica delle Marche</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marianna Capecci, MD PhD</last_name>
    <phone>+390715964043</phone>
    <email>m.capecci@univpm.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Neurorehabilitation Clinic, University Hospital Ospedali Riuniti di Ancona</name>
      <address>
        <city>Ancona</city>
        <zip>60122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marianna Capecci, Prof</last_name>
      <phone>0715964043</phone>
      <email>m.capecci@univpm.it</email>
    </contact>
    <investigator>
      <last_name>Marianna Capecci, Prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michela Coccia, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lauredana Ercolani, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michela Aringolo, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elisa Andrenelli, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lucia Pepa, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rossella Cima, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria Gabriella Ceravolo, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Ceravolo MG, de Sire A, Andrenelli E, Negrini F, Negrini S. Systematic rapid &quot;living&quot; review on rehabilitation needs due to COVID-19: update to March 31st, 2020. Eur J Phys Rehabil Med. 2020 Jun;56(3):347-353. doi: 10.23736/S1973-9087.20.06329-7. Epub 2020 Apr 22.</citation>
    <PMID>32316718</PMID>
  </reference>
  <reference>
    <citation>Andrenelli E, Negrini F, de Sire A, Arienti C, Patrini M, Negrini S, Ceravolo MG; International Multiprofessional Steering Committee of Cochrane Rehabilitation REH-COVER action. Systematic rapid living review on rehabilitation needs due to COVID-19: update to May 31st, 2020. Eur J Phys Rehabil Med. 2020 Aug;56(4):508-514. doi: 10.23736/S1973-9087.20.06435-7. Epub 2020 Jun 16.</citation>
    <PMID>32539312</PMID>
  </reference>
  <reference>
    <citation>de Sire A, Andrenelli E, Negrini F, Negrini S, Ceravolo MG. Systematic rapid living review on rehabilitation needs due to COVID-19: update as of April 30th, 2020. Eur J Phys Rehabil Med. 2020 Jun;56(3):354-360. doi: 10.23736/S1973-9087.20.06378-9. Epub 2020 May 15.</citation>
    <PMID>32408729</PMID>
  </reference>
  <reference>
    <citation>Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. J Clin Neurosci. 2020 Jul;77:8-12. doi: 10.1016/j.jocn.2020.05.017. Epub 2020 May 6.</citation>
    <PMID>32409215</PMID>
  </reference>
  <reference>
    <citation>Yang LL, Yang T. Pulmonary rehabilitation for patients with coronavirus disease 2019 (COVID-19). Chronic Dis Transl Med. 2020 May 14;6(2):79-86. doi: 10.1016/j.cdtm.2020.05.002. eCollection 2020 Jun.</citation>
    <PMID>32411496</PMID>
  </reference>
  <reference>
    <citation>Brugliera L, Spina A, Castellazzi P, Cimino P, Arcuri P, Negro A, Houdayer E, Alemanno F, Giordani A, Mortini P, Iannaccone S. Nutritional management of COVID-19 patients in a rehabilitation unit. Eur J Clin Nutr. 2020 Jun;74(6):860-863. doi: 10.1038/s41430-020-0664-x. Epub 2020 May 20. No abstract available.</citation>
    <PMID>32433599</PMID>
  </reference>
  <reference>
    <citation>Negrini S, Grabljevec K, Boldrini P, Kiekens C, Moslavac S, Zampolini M, Christodoulou N. Up to 2.2 million people experiencing disability suffer collateral damage each day of COVID-19 lockdown in Europe. Eur J Phys Rehabil Med. 2020 Jun;56(3):361-365. doi: 10.23736/S1973-9087.20.06361-3. Epub 2020 May 8.</citation>
    <PMID>32383576</PMID>
  </reference>
  <reference>
    <citation>Bartolo M, Intiso D, Lentino C, Sandrini G, Paolucci S, Zampolini M; Board of the Italian Society of Neurological Rehabilitation (SIRN). Urgent Measures for the Containment of the Coronavirus (Covid-19) Epidemic in the Neurorehabilitation/Rehabilitation Departments in the Phase of Maximum Expansion of the Epidemic. Front Neurol. 2020 Apr 30;11:423. doi: 10.3389/fneur.2020.00423. eCollection 2020.</citation>
    <PMID>32425880</PMID>
  </reference>
  <reference>
    <citation>Lew HL, Oh-Park M, Cifu DX. The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals. Am J Phys Med Rehabil. 2020 Jul;99(7):571-572. doi: 10.1097/PHM.0000000000001460.</citation>
    <PMID>32371624</PMID>
  </reference>
  <reference>
    <citation>Li H, Xue Q, Xu X. Involvement of the Nervous System in SARS-CoV-2 Infection. Neurotox Res. 2020 Jun;38(1):1-7. doi: 10.1007/s12640-020-00219-8. Epub 2020 May 13.</citation>
    <PMID>32399719</PMID>
  </reference>
  <reference>
    <citation>Valenzuela PL, Joyner M, Lucia A. Early mobilization in hospitalized patients with COVID-19. Ann Phys Rehabil Med. 2020 Jul;63(4):384-385. doi: 10.1016/j.rehab.2020.04.005. Epub 2020 May 18. No abstract available.</citation>
    <PMID>32418848</PMID>
  </reference>
  <reference>
    <citation>Stein J, Visco CJ, Barbuto S. Rehabilitation Medicine Response to the COVID-19 Pandemic. Am J Phys Med Rehabil. 2020 Jul;99(7):573-579. doi: 10.1097/PHM.0000000000001470.</citation>
    <PMID>32433243</PMID>
  </reference>
  <reference>
    <citation>Wang X, Xu H, Jiang H, Wang L, Lu C, Wei X, Liu J, Xu S. Clinical features and outcomes of discharged coronavirus disease 2019 patients: a prospective cohort study. QJM. 2020 Sep 1;113(9):657-665. doi: 10.1093/qjmed/hcaa178.</citation>
    <PMID>32442308</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>April 26, 2021</last_update_submitted>
  <last_update_submitted_qc>April 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Università Politecnica delle Marche</investigator_affiliation>
    <investigator_full_name>Marianna Capecci, PhD</investigator_full_name>
    <investigator_title>Prof</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Rehabilitation</keyword>
  <keyword>Recovery of Function</keyword>
  <keyword>Activities of Daily Living</keyword>
  <keyword>Prognosis</keyword>
  <keyword>Quality of Life</keyword>
  <keyword>Continuity of Patient Care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The research results will be made available through indexed Journals as scientific publication.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04456036
org study id: NeuroRehabAN_Covid_2020
nct id: NCT04456036
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to apply a prospective observational design to describe the
      emerging functional impairments of subjects affected by COVID-19 in the acute phase and
      monitor their course and impact on activities and participation up to 12 months of onset. The
      ultimate goal is to provide a reliable framework to plan rehabilitation delivery to COVID-19
      survivors in each phase and foresee health needs in the medium and long term. The secondary
      objective of the study is to find predictors of functional recovery, among pre-existing and
      emerging individual and contextual factors, with a special focus on the latency of
      rehabilitation start after hospital admission.
The disease caused by SARS-CoV-2 infection, COronaVIrus Disease-19 (COVID-19), was first
      reported on December 31, 2019. About 20% patients, mostly elderly people, suffered from a
      severe form of acute respiratory failure. COVID-19 is a new clinical entity, therefore its
      understanding is largely incomplete, in particular as regards medium and long term
      consequences both in the clinical and functional domain. An early integration of
      rehabilitation care since the acute phase is often required to cope with the functional
      sequelae of the severe respiratory syndromes, as well of cardiac and neurological
      complications. However, indications, approaches, timing, amount and settings are mainly
      unknown due to the lack of epidemiological data regarding the impact of COVID-19 in terms of
      body function impairment and activity limitations in the short term and participation
      restrictions in the medium and long-term.

      The purpose of the study is to apply a prospective observational design to describe the
      emerging functional impairments of subjects affected by COVID-19 in the acute phase and
      monitor their course and impact on activities and participation up to 12 months of onset. The
      ultimate goal is to provide a reliable framework to plan rehabilitation delivery to COVID-19
      survivors in each phase and foresee health needs in the medium and long term. The secondary
      objective of the study is to find predictors of functional recovery, among pre-existing and
      emerging individual and contextual factors, with a special focus on the latency of
      rehabilitation start after hospital admission.

      The study protocol complements measures of functioning with the indicators used in the
      registration form for clinical characterization cases disseminated by the World Health
      Organization: in doing so, the authors aim to support the global project of providing Member
      States with a standardized approach to collect clinical data.

      Study objectives Primary Objective: To describe the emerging functional impairments in
      patients hospitalized for SARS-COV-2 infection (COVID-19), and monitor their course and
      impact on activities and participation up to 12 months of onset Secondary Objective: To
      search for predictive factors of recovery, among the pre-existing and emerging individual and
      context-related ones. Particular attention will be paid to the presence and latency of
      rehabilitation delivery after hospital admission, describing the functional evolution of
      subjects who received rehabilitation since the acute phase, compared to those who did not.

      MATERIALS AND METHODS. Study Design. Prospective observational study with 12-month follow-up.
      Total study duration: 18 months Population. Adults, male and female, admitted to the
      University Hospital "Ospedali Riuniti of Ancona" (UH-ORA) from March 1st, 2020 for the
      management of acute COVID-19 infection, able to provide written or oral informed consent. The
      only exclusion criterion will be the lack of information concerning clinical data regarding
      the management in the acute ward.

      Data collection: A paper CRF and an eCRF will be implemented to record patients' data

        -  Clinical, laboratory and instrumental data collected in the acute phase will be
           retrieved, retrospectively, from patients' clinical records.

        -  Data concerning function impairments, activity limitations and participation
           restrictions will be collected through direct assessment carried out by the
           rehabilitation team at the enrollment, on the first referral of the patient for
           counseling (T0) and at hospital discharge (Td) (for those who will receive
           rehabilitation in the acute ward), as well as at 3 , 6 and 12 months of COVID-19
           diagnosis (T3, T6, T12). Patient reported outcomes will be assessed through
           questionnaires and interviews, also delivered by telephone or video-consultation.

      The primary endpoint is the change in the overall health status observed at enrolment (T0),
      compared to the pre-COVID-19 condition, and its evolution at 3, 6 and 12 months. To this aim,
      we will assess:

        -  independence in activities of daily living (ADLs), by the modified Rankin scale. The
           modified Rankin scale is a rapid and validated measure of global independence in ADL
           with a score ranging from 0 (no disability) to 5 (bedridden). To assess changes, the
           pre-COVID mod. Rankin scale score, retrospectively ascertained, will be compared to the
           scores prospectively collected at enrolment and at 3, 6 and 12 months

        -  walking performance, by the Walking Handicap scale (WHS). The Walking Handicap scale is
           a quick and validated measure of walking performance, with a score ranging from 1
           (Physiological walker: Walks for exercise only either at home or in parallel bars during
           physical therapy) to 6 (Community walker: Independent in all home and community
           activities. Can accept crowds and uneven terrain. Demonstrates complete independence in
           shopping centers). To assess changes, the pre-COVID WHS score, retrospectively
           ascertained, will be compared to the scores prospectively collected at 3, 6 and 12
           months

        -  health-related quality of life perception, by the 36-Item Short Form Survey (SF-36).
           SF-36 is a widespread validated scale assessing patient-reported changes in
           health-related well-being perception over the last 4 weeks. SF-36 scores will be
           collected at 3, 6 and 12 months.

      The secondary endpoint is the identification of the predictors of functional recovery at 3, 6
      and 12 months, among the pre-existing and emerging individual and context-related factors.

      The following explanatory variables will be considered:

        -  Pre-existing individual factors: age, gender, blood type, nutritional status,
           comorbidity (Modified Cumulative Illness Rating Scale - CIRS), life habits and
           pre-existing disability (modified Rankin Scale and Walking Handicap scale in pre-COVID
           phase)

        -  Emerging individual factors: severity of COVID-19 on admission to the acute ward,
           severity of pneumonia during hospitalization (according to Li et al 2020), blood
           chemistry (e.g. levels of interleukine, albumin, creatinine, CRP), pulmonary
           thromboembolism, neurologic complications, swallow disorders in the acute phase;
           severity of body function impairment and activity limitation on enrolment (as measured
           by the Trunk control test-TCT, Standing Balance-SB, Functional Ambulation Category-FAC,
           modified Barthel index- mBI, Montreal Cognitive Assessment-MoCA)

        -  Emerging context-related factors: drug treatment in the acute phase (e.g. ACE
           inhibitors, Angiotensin II receptor blockers, Nonsteroidal anti-inflammatories,
           Antivirals, heparin), procedures adopted in the ICU (prone positioning, tracheostomy,
           support for ventilation, ECMO, Renal replacement therapy or dialysis,
           Inotropes/vasopressors), rehabilitation delivery in the acute ward and latency from
           hospital admission to rehabilitation start.

      Clinical-functional evaluations will be carried out at the following time-points:

      T0 = on enrolment Td = discharge from the acute ward (only for subjects who are enrolled
      during their stay in the acute ward) T3, T6, T12 = three, six and 12 months after hospital
      admission due to COVID-19 infection.

      After discharge from hospital, the assessments will be carried out in the outpatient
      laboratory; in case of mobility restrictions, questionnaires will be delivered and interviews
      will be conducted by telephone or by video consulting.

      Sample size and data analysis. Given the nature of the study, a formal calculation of the
      sample size was not made. The enrolment of at least 100 subjects is estimated based on
      COVID-19 incidence in the catchment population of the UH-ORA.

      A descriptive analysis will be conducted on the collected variables using point estimates and
      variability measures for quantitative variables or absolute and relative frequencies for
      category variables.

      A multivariate model will be constructed to extrapolate predictors of poor recovery at 12
      months (i.e. Delta T12-T0 on modified Rankin score : >1), by adjusting for potential
      confounders. After checking for the normal distribution of quantitative measures, the
      analysis of variance (ANOVA) for repeated measures will be applied to analyze the
      distribution of functional outcome measures, at 3, 6 and 12 months, among those who received
      rehabilitation in the acute phase, respect to those who did not.
observational model: Cohort
time perspective: Prospective
measure: Change from pre-COVID-19 condition in ADL independence on the mod. Rankin scale score at the enrolment (T0) assessment, at 3, 6 and 12 months
time frame: Pre-COVID status, at enrolment and at 3, 6 12-month follow-up
description: mod. Rankin scale is a rapid and validated measure of global independence in ADL with a score ranging from 0 (no disability) to 5 (bedridden).
Change= pre-COVID mod. Rankin scale score (retrospective data) - mod. Rankin scale score prospectively collected at the enrolment (T0) and at 3, 6 and 12 months
measure: Change from pre-COVID-19 condition in walking performance on the Walking Handicap scale (WHS) at 3, 6 and 12 months
time frame: Pre-COVID status , and 3, 6 12-month follow-up
description: The Walking Handicap scale is a quick and validated measure of walking performance, with a score ranging from 1 (Physiological walker: Walks for exercise only either at home or in parallel bars during physical therapy) to 6 (Community walker: Independent in all home and community activities. Can accept crowds and uneven terrain. Demonstrates complete independence in shopping centers).
Change= pre-COVID WHS (retrospective data) - WHS score prospectively collected at 3, 6 and 12 months
measure: Patient-reported health-related well-being perception on the 36-Item Short Form Survey - SF-36 at 3, 6 12 months follow-up
time frame: 3, 6 and 12-month follow-up
description: SF-36 is a widespread validated scale assessing patient-reported changes in health-related well-being perception over the last 4 weeks
measure: Change in global ADL disability on modified Barthel Index (mBI), from the enrolment (T0), at 3, 6 12 months follow-up
time frame: the enrolment (T0) assesssment and 3, 6 and 12-month follow-up
description: The mBI is a validated measure of physical disability widely used to assess individual behavior in activities of daily living for patients with disabling conditions. It measures what patients do in practice. Score assignment can be made without any previous formal training.
Change = mBI score at the enrolment (T0) assessment - mBI score at 3, 6 and 12-month follow-up
measure: Change in walking capacity on Functional Ambulation Category (FAC), from the enrolment (T0) assessment, at 3, 6 12 months follow-up
time frame: Pre-COVID status, the enrollment (T0) assessment and 3, 6 12-month follow-up
description: FAC is a validated measures of gait capacity with a score ranging from 0 (unable to walk) to 5 (able to walk independently in any environment)
Change= pre-COVID FAC score (retrospective data) - FAC score prospectively collected at the enrolment (T0) assessment and at 3, 6 and 12 months
measure: Change in cognitive abilities on the Montreal Cognitive Assessment (MoCA) from the enrollment (T0) assessment, at 3, 6 12 months follow-up
time frame: the enrollment (T0) assessment and 3, 6 and 12-month assessment follow-up
description: The MoCA is a cognitive screening test designed to assist health professionals in the detection of mild cognitive impairment. It is especially sensitive at detecting dysfunctions in executive strategies.
Change = MoCA score at the enrollment (T0) - MoCA score at 3, 6 and 12-month follow-up
measure: Change in patient-reported pain on Numerical Rating Scale from the enrollment (T0) assessment, at 3, 6 12 months follow-up
time frame: the enrollment (T0) and 3, 6 and 12-month assessment follow-up
description: Pain NRS is a widespread validate assessment tool measuring pain perception with a score ranging from 0 (no pain), to 10 (worst ever pain).
Change= NRS score at the enrollment (T0) assessment - NRS score at 3, 6 and 12-month follow-up
measure: Change in swallow abilities on Dysphagia Outcome Severity Scale (DOSS) from the first functional assessment in acute care, at 3, 6 12 months follow-up
time frame: the enrollment (T0) assessment and 3, 6 and 12-month assessment follow-up
description: DOSS is a simple, easy-to-use, 7-point scale developed to systematically rate the functional severity of dysphagia based on objective assessment, with a score ranging from 1 (severe dysphagia: Non Per oral nutrition) to 7 ( Full per oral nutrition).
Change= DOSS score at enrolment (T0) - DOSS score at 3, 6 and 12-month follow-up
measure: Change in endurance on 6-Minutes Walking Test (6MWT) from the enrolment (T0) assessment, at 3, 6 12 months follow-up
time frame: the enrolment (T0) and 3, 6 and 12-month assessment follow-up
description: 6MWT is a validated and synthetic measure of endurance influenced by cardio-respiratory and motor function impairment.
Change = 6MWT on enrolment (T0) - 6MWT score at 3, 6 and 12-month follow-up
measure: Change in mood status on Beck Depression Inventory (BDI) from the enrolment (T0) assessment, at 3, 6 and 12 month follow-up
time frame: enrolment (T0) assessment and 3, 6 and 12-month assessment follow-up
description: The BDI is a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression.
Change = BDI on enrolment (T0) assessment - BDI score at 3, 6 and 12-month follow-up
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria Gabriella Ceravolo, MD PhD
role: Study Director
affiliation: Dep. of Experimental and Clinical Medicine - University Politecnica delle Marche
last name: Marianna Capecci, MD PhD
phone: +390715964043
email: m.capecci@univpm.it
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Italy
citation: Ceravolo MG, de Sire A, Andrenelli E, Negrini F, Negrini S. Systematic rapid "living" review on rehabilitation needs due to COVID-19: update to March 31st, 2020. Eur J Phys Rehabil Med. 2020 Jun;56(3):347-353. doi: 10.23736/S1973-9087.20.06329-7. Epub 2020 Apr 22.
PMID: 32316718
citation: Andrenelli E, Negrini F, de Sire A, Arienti C, Patrini M, Negrini S, Ceravolo MG; International Multiprofessional Steering Committee of Cochrane Rehabilitation REH-COVER action. Systematic rapid living review on rehabilitation needs due to COVID-19: update to May 31st, 2020. Eur J Phys Rehabil Med. 2020 Aug;56(4):508-514. doi: 10.23736/S1973-9087.20.06435-7. Epub 2020 Jun 16.
PMID: 32539312
citation: de Sire A, Andrenelli E, Negrini F, Negrini S, Ceravolo MG. Systematic rapid living review on rehabilitation needs due to COVID-19: update as of April 30th, 2020. Eur J Phys Rehabil Med. 2020 Jun;56(3):354-360. doi: 10.23736/S1973-9087.20.06378-9. Epub 2020 May 15.
PMID: 32408729
citation: Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. J Clin Neurosci. 2020 Jul;77:8-12. doi: 10.1016/j.jocn.2020.05.017. Epub 2020 May 6.
PMID: 32409215
citation: Yang LL, Yang T. Pulmonary rehabilitation for patients with coronavirus disease 2019 (COVID-19). Chronic Dis Transl Med. 2020 May 14;6(2):79-86. doi: 10.1016/j.cdtm.2020.05.002. eCollection 2020 Jun.
PMID: 32411496
citation: Brugliera L, Spina A, Castellazzi P, Cimino P, Arcuri P, Negro A, Houdayer E, Alemanno F, Giordani A, Mortini P, Iannaccone S. Nutritional management of COVID-19 patients in a rehabilitation unit. Eur J Clin Nutr. 2020 Jun;74(6):860-863. doi: 10.1038/s41430-020-0664-x. Epub 2020 May 20. No abstract available.
PMID: 32433599
citation: Negrini S, Grabljevec K, Boldrini P, Kiekens C, Moslavac S, Zampolini M, Christodoulou N. Up to 2.2 million people experiencing disability suffer collateral damage each day of COVID-19 lockdown in Europe. Eur J Phys Rehabil Med. 2020 Jun;56(3):361-365. doi: 10.23736/S1973-9087.20.06361-3. Epub 2020 May 8.
PMID: 32383576
citation: Bartolo M, Intiso D, Lentino C, Sandrini G, Paolucci S, Zampolini M; Board of the Italian Society of Neurological Rehabilitation (SIRN). Urgent Measures for the Containment of the Coronavirus (Covid-19) Epidemic in the Neurorehabilitation/Rehabilitation Departments in the Phase of Maximum Expansion of the Epidemic. Front Neurol. 2020 Apr 30;11:423. doi: 10.3389/fneur.2020.00423. eCollection 2020.
PMID: 32425880
citation: Lew HL, Oh-Park M, Cifu DX. The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals. Am J Phys Med Rehabil. 2020 Jul;99(7):571-572. doi: 10.1097/PHM.0000000000001460.
PMID: 32371624
citation: Li H, Xue Q, Xu X. Involvement of the Nervous System in SARS-CoV-2 Infection. Neurotox Res. 2020 Jun;38(1):1-7. doi: 10.1007/s12640-020-00219-8. Epub 2020 May 13.
PMID: 32399719
citation: Valenzuela PL, Joyner M, Lucia A. Early mobilization in hospitalized patients with COVID-19. Ann Phys Rehabil Med. 2020 Jul;63(4):384-385. doi: 10.1016/j.rehab.2020.04.005. Epub 2020 May 18. No abstract available.
PMID: 32418848
citation: Stein J, Visco CJ, Barbuto S. Rehabilitation Medicine Response to the COVID-19 Pandemic. Am J Phys Med Rehabil. 2020 Jul;99(7):573-579. doi: 10.1097/PHM.0000000000001470.
PMID: 32433243
citation: Wang X, Xu H, Jiang H, Wang L, Lu C, Wei X, Liu J, Xu S. Clinical features and outcomes of discharged coronavirus disease 2019 patients: a prospective cohort study. QJM. 2020 Sep 1;113(9):657-665. doi: 10.1093/qjmed/hcaa178.
PMID: 32442308
responsible party type: Principal Investigator
investigator affiliation: Università Politecnica delle Marche
investigator full name: Marianna Capecci, PhD
investigator title: Prof
mesh term: COVID-19
sharing ipd: No
ipd description: The research results will be made available through indexed Journals as scientific publication.