Apixaban versus Dalteparin for the Treatment of Acute Venous Thromboembolism in Patients with Cancer: The Caravaggio Study

Giancarlo Agnelli; Cecilia Becattini; Rupert Bauersachs; Benjamin Brenner; Mauro Campanini; Alexander Cohen; Jean Marie Connors; Andrea Fontanella; Gualberto Gussoni; Menno V. Huisman; Catherine Lambert; Guy Meyer; Andres Muñoz; Joaquim Abreu de Sousa; Adam Torbicki; Melina Verso; Giorgio Vescovo; for the Caravaggio Study Investigators

doi:10.1055/s-0038-1668523

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2018; 118(09): 1668-1678
DOI: 10.1055/s-0038-1668523

Trial Protocol Design Paper

Georg Thieme Verlag KG Stuttgart · New York

Apixaban versus Dalteparin for the Treatment of Acute Venous Thromboembolism in Patients with Cancer: The Caravaggio Study

Giancarlo Agnelli

¹Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy

,

Cecilia Becattini

¹Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy

,

Rupert Bauersachs

²Department of Vascular Medicine, Klinikum Darmstadt GmbH, Darmstadt, Germany

³Centre for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany

,

Benjamin Brenner

⁴Institute of Hematology and BMT, Rambam Health Care Campus, Technion – Israel Institute of Technology, Haifa, Israel

,

Mauro Campanini

⁵Department of Medicine, Azienda Ospedaliero Universitaria “Maggiore della Carità,” Novara, Italy

,

Alexander Cohen

⁶Guy's and St Thomas' NHS Foundation Trust Hospital, King's College London, London, United Kingdom

,

Jean Marie Connors

⁷Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

,

Andrea Fontanella

⁸Department of Medicine, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy

,

Gualberto Gussoni

⁹Fadoi Research Center, Milan, Italy

,

Menno V. Huisman

¹⁰Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden University, Leiden, The Netherlands

,

Catherine Lambert

¹¹Division of Hematology, Thrombosis and Hemostasis Unit, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium

,

Guy Meyer

¹²Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France

¹³Université Paris Descartes, Sorbonne Paris Cité, Paris France

,

Andres Muñoz

¹⁴Medical Oncology Department, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, Spain

,

Joaquim Abreu de Sousa

¹⁵Surgical Oncology Department, Institut Português Oncologie, Porto FG, EPE, Porto, Portugal

,

Adam Torbicki

¹⁶Departments of Pulmonary Hypertension, Thromboembolic Disease and Cardiology, Medical Center for Postgraduate Education, Otwock, Poland

,

Melina Verso

¹Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy

,

Giorgio Vescovo

¹⁷Internal Medicine, S. Antonio Hospital, Padua, Italy

,

for the Caravaggio Study Investigators

› Author Affiliations

Abstract

International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years (β = 80%; α one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.

Keywords

venous thromboembolism - cancer - apixaban

Full Text

References

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Supplementary Material

Supplementary Material