External Validation of the CLOVER Score for Detecting Occult Cancer in Venous Thromboembolism Patients
NCT ID: NCT07310693
Last Updated: 2025-12-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
500 participants
OBSERVATIONAL
2025-12-01
2028-12-31
Brief Summary
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Detailed Description
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Retrospective cohort:
Patients aged ≥18 years with objectively confirmed symptomatic deep vein thrombosis (DVT) and/or pulmonary embolism (PE) diagnosed between January 1, 2000, and August 31, 2022, in participating hospitals across Spain will be included. Patients from centers involved in the model derivation (Hospital Universitario Infanta Leonor and Hospital Universitario de Fuenlabrada) will be excluded. Cases are defined as patients with a histologically confirmed cancer diagnosis occurring between 1 and 24 months after the index VTE event. Controls are defined as patients without a cancer diagnosis during the same period. All variables required for the CLOVER model (age, D-dimer, systolic blood pressure, ALT, hemoglobin, creatinine, total cholesterol, platelet count, triglycerides, leukocyte count, weight, chronic lung disease, heart rate, sex, and previous VTE recurrence) will be extracted from electronic health records using a standardized data collection form. The CLOVER model will be applied to each patient to assess its discrimination for cancer prediction in the retrospective cohort.
Prospective cohort:
From December 1, 2025, to December 31, 2027, consecutive adult patients with objectively confirmed symptomatic VTE will be recruited in participating hospitals. All patients will undergo a standard clinical evaluation including medical history, physical examination, basic laboratory testing (complete blood count and biochemistry), chest X-ray, and age- and sex-appropriate cancer screening tests according to clinical practice guidelines. The CLOVER score will be calculated at the time of VTE diagnosis using a dedicated web-based tool (CLOVER-Web). Patients will be classified as "low risk" or "high risk" based on the optimal F1-score threshold (0.487), corresponding to a sensitivity of 51%, specificity of 95%, PPV of 46%, and NPV of 96%. All participants will be followed for at least two years to determine whether an occult cancer is diagnosed. Further diagnostic testing for suspected cancer will be performed at the discretion of the treating physician, regardless of CLOVER result.
Model performance and bias assessment:
The external validation will evaluate model discrimination using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the ROC curve (AUC). Additional analyses will assess potential prediction bias across demographic and clinical subgroups (e.g., age, sex, comorbidities). Model calibration and temporal performance will also be reviewed, with predefined procedures for identifying deviations from expected behavior. Weekly reports during the prospective phase will alert investigators to performance drift or potential implementation issues in the web-based tool.
Clinician satisfaction:
A secondary objective is to evaluate clinician satisfaction with the CLOVER-Web tool. An online questionnaire specifically designed for this study will be administered to participating clinicians to assess usability, clarity, and clinical utility.
Ethical considerations:
The study follows the Declaration of Helsinki and Spanish regulations on biomedical research and data protection. Retrospective data collection will request exemption from informed consent due to the use of anonymized clinical information. Prospective participants will provide written or electronic informed consent. All data will be pseudonymized and stored securely.
Conditions
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Keywords
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Prospective VTE Cohort
Adults with objectively confirmed symptomatic venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) consecutively enrolled from December 2025 to December 2027 in participating hospitals. All participants will undergo routine clinical evaluation, laboratory testing, and cancer screening according to standard practice. The CLOVER score will be calculated at baseline using the web-based tool (CLOVER-Web).
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* Objectively confirmed acute symptomatic venous thromboembolism (deep vein thrombosis and/or pulmonary embolism).
* Ability to provide written or electronic informed consent.
Exclusion Criteria
* Participation in another interventional study that may interfere with outcomes.
* Inability or refusal to provide informed consent.
18 Years
ALL
No
Sponsors
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Fundación para la Investigación e Innovación Biomédica del Hospital Universitario Infanta Leonor
UNKNOWN
Infanta Leonor University Hospital
OTHER
Responsible Party
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Anabel Franco Moreno
Specialist in Internal Medicine
Principal Investigators
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Anabel Franco-Moreno, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital Universitario Infanta Leonor
Franco-Moreno, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Hospital Universitario Infanta Leonor
Locations
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Hospital Clínic
Barcelona, Barcelona, Spain
Hospital Universitario Infanta Leonor
Madrid, Madrid, Spain
Hospital Universitario La Paz
Madrid, Madrid, Spain
Hospital Universitario Príncipe de Asturias
Madrid, Madrid, Spain
Hospital Universitatio del Sureste
Madrid, Madrid, Spain
Hospital Universitario de Móstoles
Madrid, Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, Murcia, Spain
Hospital Universitario Morales Meseguer
Murcia, Murcia, Spain
Hospital San Agustín
Avilés, Principality of Asturias, Spain
Hospital Universitario Son Llatzer
Balea, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario de Fuenlabrada
Madrid, , Spain
Countries
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Central Contacts
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Facility Contacts
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JESUS AIBAR, MD, PhD
Role: primary
Anabel Franco Moreno, MD, PhD
Role: primary
Teresa Sancho, MD
Role: primary
f garcia sanchez, MD
Role: primary
Ana Mancebo Plaza, MD
Role: primary
Andrea Pérez, MD
Role: primary
Leticia Guirado Torrecillas, MD
Role: primary
Javier Pagán, MD, PhD
Role: primary
José Ferreiro Celeiro, MD
Role: primary
Elena Cisneros de la Fuente, MD
Role: primary
Jose Bascuñana Morejon de Giron, MD, PhD
Role: primary
Cristina De Ancos Aracil, MD
Role: primary
References
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Franco-Moreno A, Madronal-Cerezo E, de Ancos-Aracil CL, Farfan-Sedano AI, Munoz-Rivas N, Bascunana Morejon-Giron J, Ruiz-Giardin JM, Alvarez-Rodriguez F, Prada-Alonso J, Gala-Garcia Y, Casado-Suela MA, Bustamante-Fermosel A, Alfaro-Fernandez N, Torres-Macho J; CLOVER Research Group. Development of a Predictive Model of Occult Cancer After a Venous Thromboembolism Event Using Machine Learning: The CLOVER Study. Medicina (Kaunas). 2024 Dec 27;61(1):18. doi: 10.3390/medicina61010018.
Other Identifiers
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CLOVER_validation
Identifier Type: -
Identifier Source: org_study_id