Real-world Study on Bemiparin Effect in Patients with Cancer-Associated Thromboembolism Using Artificial Intelligence (BEMICAT Study)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  This is a retrospective, multicenter observational cohort study designed as a target trial emulation. ; It uses real-world data from electronic health records (EHRs) to assess the comparative effectiveness and safety of bemiparin versus other low molecular weight heparins in patients with cancer-associated thrombosis (CAT).; ; The study identifies a cohort of adult patients with active cancer and objectively confirmed venous thromboembolism (VTE), and follows them from the time of diagnosis (time zero) for seven months. ; Patients are classified according to the anticoagulant received, and only those treated with full-dose, long-term therapy are included in the per-protocol analysis.; The design emulates key elements of a randomized trial, including eligibility criteria, alignment of follow-up with treatment initiation, and prespecified censoring rules. ; Data are extracted using natural language processing (NLP) and machine learning (ML) technologies to convert unstructured clinical texts into structured variables for analysis.

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (B01AB12) bemiparin

  bemiparin

  (B01AB04) dalteparin

  dalteparin

  (B01AB05) enoxaparin

  enoxaparin

  (B01AB10) tinzaparin

  tinzaparin
• Additional medical condition(s):
  cancer-associated thrombosis

Population studied

• Short description of the study population:
  The study will include adult patients (aged ≥18 years) with active cancer and an objectively confirmed diagnosis of cancer-associated thrombosis (CAT), defined as deep vein thrombosis (DVT), pulmonary embolism (PE), or both. Active cancer will be defined as a cancer diagnosis, cancer treatment, or metastatic disease within the six months prior to the thrombotic event, or a hematologic malignancy not in complete remission. ; Patients will be identified from participating Spanish hospitals between January 2015 and June 2024, and will have initiated long-term anticoagulation with bemiparin, dalteparin, enoxaparin, or tinzaparin. ; Pregnant individuals, those with only non-melanoma skin cancer or basal cell carcinoma, and patients with a prior VTE episode within 12 months before the index event will be excluded.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  The study is restricted to adult cancer patients with venous thromboembolism and does not include specific analyses of special populations beyond the target population.
• Estimated number of subjects:
  5900

Study design details

• Study design:
  Multicenter, retrospective, observational cohort study emulating a target trial, using electronic health records and NLP to compare the effectiveness and safety of bemiparin versus other LMWHs in cancer-associated thrombosis.
• Main study objective:
  The main objective of the BEMICAT study is to assess the non-inferiority of long-term, full-dose treatment with bemiparin in preventing recurrent venous thromboembolism (VTE) in adult patients with cancer-associated thrombosis (CAT), compared to pooled data from patients treated with dalteparin, enoxaparin, or tinzaparin. Effectiveness will be evaluated over a six-month period following the index thrombotic event.; ; In addition, the study aims to compare the safety profile of bemiparin versus the comparator low molecular weight heparins (LMWHs), with particular attention to the incidence of major bleeding events during the same follow-up period.
• Setting:
  This study will be conducted using EHRs from multiple hospitals across Spain. ; The study period spans from January 1, 2014 to January 31, 2025, with the recruitment period from January 1, 2015 to June 30, 2024.; The population includes adult patients (≥18 years) with active cancer and objectively confirmed VTE (DVT, PE, or both). Patients will be identified using NLP applied to unstructured EHR data, complemented by structured clinical variables.; Patients will be assigned to treatment arms based on the LMWH received: bemiparin (exposed group) versus pooled comparators (dalteparin, enoxaparin, tinzaparin). ; Follow-up will begin at the time of CAT diagnosis (time zero) and will continue for 6 months or until censoring due to treatment discontinuation or switch, recurrent VTE, death, loss to follow-up, or administrative study end.
• Comparators:
  The comparators in this study are LMWHs commonly used for the treatment of CAT: dalteparin, enoxaparin, and tinzaparin. ; These will be pooled into a single comparator group and analyzed against bemiparin in a per-protocol framework. Treatment allocation is not randomized but based on real-world prescribing patterns captured in EHRs. ; Patients included in the comparator group must meet the same eligibility criteria and receive long-term, full-dose LMWH therapy, initiated within the defined time window after the index CAT event.
• Outcomes:
  The study will evaluate effectiveness, safety, and treatment-related outcomes during a six-month follow-up period after the index CAT event. The primary effectiveness outcome is symptomatic VTE recurrence. ; Secondary effectiveness outcomes include incidental VTE recurrence, stroke, acute myocardial infarction, and all-cause death. ; The primary safety outcome is major bleeding. ; Secondary safety outcomes include clinically relevant non-major bleeding and other clinically relevant bleeding events. ; Treatment-related outcomes will assess anticoagulation patterns, including persistence and treatment switches between LMWHs.
• Data analysis plan:
  Phase I will estimate the annual incidence of CAT in patients initiating long-term treatment with bemiparin using a predictive model adjusted for hospital type, population, and year. ; Phase II will assess the per-protocol effect of bemiparin versus pooled LMWHs (dalteparin, enoxaparin, tinzaparin) in preventing VTE recurrence and evaluating safety over 6 months, following a target trial emulation framework. Risk estimation for time-to-event outcomes will use weighted pooled logistic regression, with a noninferiority margin of 1.5. Cloning, censoring, and time-varying inverse probability weighting will address treatment assignment and selection bias. Effect modification (e.g., index DVT vs PE) will be included in model specification.; ; Descriptive statistics will summarize baseline characteristics, treatment patterns, and switch rates. Cumulative incidence functions will be used to estimate time-to-event outcomes accounting for competing risks. ; Validity of NLP-extracted population, intervention, and outcome definitions will be assessed against a reference standard by a blinded adjudication committee using sensitivity, specificity, PPV, NPV, and ICC. ; Missing data will not be imputed; results will reflect observed data and missingness will be reported explicitly.