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FOUND - Ancillary Study to Smile Protocol NCT03654105 (FOUND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04441814
Recruitment Status : Enrolling by invitation
First Posted : June 22, 2020
Last Update Posted : June 23, 2020
University of Parma
University of Milan
University of Milano Bicocca
Information provided by (Responsible Party):
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Brief Summary:

During the current pandemic, in Italy the majority of asymptomatic or pauci-symptomatic COVID-19 cases were not identified nor diagnosed and this fact caused a decrease in the effectiveness of the various containment measures implemented. Therefore, in a future scenario where a new viral swarm is expected, the early identification of all infected cases becomes essential to plan and activate a containment strategy for the spread of the virus, given the current absence of vaccines.

The typical radiological finding of COVID-19 is an interstitial pneumonia, which can be responsible, in a significant portion of patients, of an acute respiratory distress syndrome (ARDS).

Low-dose chest CT and simple blood tests could identify sub-solid pulmonary nodules (SSNs) indicative of COVID-19 infection in asymptomatic subjects.

Objectives of this observational study are the early detection of COVID-19 markers indicative of prior exposure or persisting viral infection in asymptomatic subjects and the assessment of the frequency and outcome of COVID-19-related SSNs in asymptomatic subjects by time, domicile, and other individual risk factors.

SMILE lung CT screening program cohort has been considered, based on 960 subjects at high lung cancer risk for tobacco smoking (≥20 pack/year) and age (50-75 years), together with inflammatory and respiratory profile. SMILE utilizes a top technology dual-source CT scanner (Somatom Force) with the lowest radiation dose ever applied to lung screening. All chest CT images from screening subjects will be re-evaluated by two additional CAD programs, specifically designed for the analysis of SSNs and quantification of the total volume of lung parenchyma showing an increased density. This re-evaluation will improve the sensitivity and specificity of radiomic assessment.

This study cohort, enriched by the already established longitudinal biobank of frozen plasma samples, represent an ideal opportunity to assess the frequency of SSNs in asymptomatic subjects, due to the effect of COVID-19, particularly among subjects living in areas at high risk of viral exposure. It will also be possible to evaluate if COVID-19-related SSNs are associated with chronic co-morbidity, other individual risk factors, inflammatory (CRP) / immunomodulatory (25(OH)D) blood profile, and/or can be traced by immune markers such as IgM/IgG and other cytokines.

Clinical data will be integrated with an analysis of the IgG-IgM profile specific for covid-19, on the plasma samples taken at the time of the CT scan, or subsequently, in collaboration with University of Milan, Luigi Devoto Work Clinic.

The lasting collaboration with the Radiological Science Department of the University of Parma in lung screening also offers the opportunity to validate the results obtained in this cohort on chest CT performed at the University Parma Hospital during the last two months in symptomatic subjects for suspected covid-19 pneumonia.

In collaboration with University of Milano Bicocca, Machine Learning (ML) tools will be applied to predict the clinical relevance, severity and ultimate outcome of SSNs, based on radiomic CT features, epidemiologic risk, co-morbidity and inflammatory/immune blood biomarkers. ML analysis will generate a predictive algorithm for clinical outcome of SSNs, and specifically the risk of COV-I9 infection and unfavorable disease prognosis.

Condition or disease
COVID 19 Inflammatory Status

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Study Type : Observational
Estimated Enrollment : 960 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Frequency and OUtcome of Sub-solid Pulmonary Nodules in Asymptomatic Subjects Tested by Chest CT Screening Versus COVID-19 Patients (FOUND) - Ancillary Study to Smile Protocol NCT03654105
Actual Study Start Date : July 23, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Lung cancer screening subjects
Subjects enrolled in SMILE lung cancer screening trial

Primary Outcome Measures :
  1. Temporal variations in the frequency and morphology of SSNs according to the COVID-19 epidemic [ Time Frame: September 2019 - February 2020 ]
    Evaluate the increase of frequency and severity of SSNs according to the COVID-19 epidemic. The results of chest CT performed in different periods will be compared (December 2019 -February 2020; September 2019 - November 2019)

  2. Geographical variations in the frequency and morphology of SSNs according to the COVID-19 epidemic [ Time Frame: September 2019 - February 2020 ]
    To this end, subjects domiciled in different geographical areas will be compared: a) high risk (≥ 200 covid cases / 100,000 inhabitants); b) medium risk (100-200 cases / 100,000); low risk (<100 cases / 100,000)

  3. Correlation between sub-solid lesions and individual risk [ Time Frame: September 2019 - February 2020 ]

    Establish whether subjects with a higher level of risk and / or individual damage have a higher frequency and / or severity of sub-solid lung injury.

    For this purpose, the following parameters will be analyzed: a) inflammatory profile (PCR), b) respiratory capacity (FEV1), c) co-morbidity (e.g. obesity, diabetes, cardio-vascular disease, COPD), d) level of CO; e) age, f) gender.

  4. Correlation between sub-solid lesions and incidence of acute events [ Time Frame: September 2019 - August 2020 ]
    Establish whether subjects with greater frequency and/or severity of sub-solid lung lesions, associated or not with other individual risk factors, have a higher incidence of acute pathological events, in particular of respiratory nature, in the three (six) months following the CT exam. For this purpose, information on the time of onset and duration of these events will be collected: fever, cough, dyspnoea, hospitalization, positivity for covid-19, treatment in the ICU, and eventual death.

Biospecimen Retention:   Samples Without DNA
Blood samples to evaluate inflammatory markers

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects who enrolled in SMILE protocol and signed the SMILE protocol NCT03654105 informed consent

Inclusion Criteria:

  • Elegibility to annual LDCT screening
  • Absence of tumors for at least 5 years
  • Signed informed consent form meet inclusion criteria outlined in SMILE Protocol NCT03654105

Exclusion Criteria:

  • Hypersensitivity to acetylsalicylic acid, salicylates or any of the excipients
  • Chronic treatment with acetylsalicylic acid, or other anti-clotting or anti-coagulant drugs
  • Treatment with methotrexate
  • Existing Mastocytosis
  • History of asthma induced by the administration of salicylates or substances to similar activity, particularly non-steroidal anti-inflammatory drugs
  • Gastroduodenal ulcer
  • Hemorrhagic diathesis
  • Severe chronic pathology
  • Serious psychiatric problems
  • Previous treatment with Cytisine
  • Abuse of alcohol or other substances

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04441814

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Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy, 20133
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
University of Parma
University of Milan
University of Milano Bicocca
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Principal Investigator: Ugo Pastorino, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Additional Information:
Publications of Results:

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Responsible Party: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano Identifier: NCT04441814    
Other Study ID Numbers: INT 49/20
First Posted: June 22, 2020    Key Record Dates
Last Update Posted: June 23, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
Lung cancer screening
Subsolid pulmonary nodules
Low dose CT screening
Blood biomarkers