Biomarkers of Thrombosis as Predictors of Venous Thromboembolism Risk in Cancer Patients

• Conditions: Cancer; Thrombosis; Thromboembolism; Biomarkers

• Registration Number: NCT04301362
• Lead Sponsor: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.

Brief Summary

The main venous thromboembolism (VTE) risk prediction model for ambulatory cancer patients is Khorana. Cancer thrombosis is associated with elevated thrombin generation. Its quantification is a promising method for evaluating patient's thrombotic profile.

This study aims to develop a predictive model of VTE risk in ambulatory cancer patients, combining thrombosis biomarkers (D-dimers and thrombin generation potential) with the Khorana score.

This is a prospective observational study that includes newly diagnosed cancer patients proposed for anti-tumor treatment (chemotherapy, immunotherapy or targeted therapies). Patients with disease progression are allowed if chemotherapy-free for 3 months. A 6-month mean incidence of VTE 6-10% is expected, requiring a sample size of 600 patients. Blood sample is collected at inclusion to analyze thrombosis biomarkers and blood count. The primary endpoint is the occurrence of symptomatic or incidental VTE within 6 months of inclusion. Models will follow a logistic approach with K-fold cross-validation (k=10). Model quality will be assessed with Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC). Decision for entering predictors in multivariate models will be based on p \<.10 in the univariate analysis.

Detailed Description

The main aims will be the following:

* Evaluate the utility of the combination of thrombosis biomarkers (D-dimers and thrombin generation potential) with the Khorana score in order to stratify VTE risk in ambulatory cancer patients;

* Determine the potential of this new score in the stratification of cancer patients into high- and low-risk VTE groups, in order to identify patients who would benefit from primary thromboprophylaxis;

* Determine the applicability of the thrombin generation test as an independent factor in the stratification of VTE risk in the cancer population under study;

* Determine the predictive value of D-dimers in the cancer population under study (high versus low risk discrimination).

Study Timeline

• Study Start: 2019-07-19
• Status Verified: 2020-03
• Study First Submitted: 2020-03-06
• Study First Submitted QC: 2020-03-06
• Study First Posted: 2020-03-10
• Last Update Submitted: 2020-03-10
• Last Update Posted: 2020-03-12
• Primary Completion: 2021-07-19
• Study Completion: 2021-12-19

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Patients older than 18 years.
• Newly diagnosed cancer patients, proposed for anti-tumor medical treatment (chemotherapy, immunotherapy and targeted therapies).
• Patients with a cancer diagnosis, previously under medical anti-tumor treatments, with disease progression proposed for a new line of anti-tumor treatment, who have not recently received chemotherapy (within the last three months).
• Follow-up in Medical Oncology, Clinical Hematology, and Pulmonology consultations at Centro Hospitalar Vila Nova de Gaia/Espinho.

Exclusion Criteria

• Major bleeding in the last 3 months.
• Major surgery in the last 28 days.
• Patients on anticoagulation/antithrombotic therapy
• Pregnant or breastfeeding women.
• Patients previously submitted to bone marrow transplantation.
• Inaccessibility to the results of the biomarkers or other elements provided for in the Khorana score.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Occurrence of symptomatic or incidental VTE	6 months	Confirmed by vascular ultrasound, thoracic angiography, and/or ventilation/perfusion scintigraphy. There will be no routine screening for VTE diagnosis. The symptomatic and incidental episodes documented in the clinical process and complementary diagnostic tests will be considered.

Secondary Outcome Measures

Name	Time	Method
Mortality	6 months	deaths per 100 persons
Risk factors for the development of VTE	6 months	Identify risk factors for the development of VTE in ambulatory cancer patients
Major Bleeding	6 months	major bleeding event

Trial Locations

Locations (1)

Centro Hospitalar Vila Nova de Gaia/Espinho; 🇵🇹 Vila Nova De Gaia, Portugal