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
1  Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
Cecilia Becattini
1  Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
Rupert Bauersachs
2  Department of Vascular Medicine, Klinikum Darmstadt GmbH, Darmstadt, Germany
3  Centre for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany
Benjamin Brenner
4  Institute of Hematology and BMT, Rambam Health Care Campus, Technion – Israel Institute of Technology, Haifa, Israel
Mauro Campanini
5  Department of Medicine, Azienda Ospedaliero Universitaria “Maggiore della Carità,” Novara, Italy
Alexander Cohen
6  Guy's and St Thomas' NHS Foundation Trust Hospital, King's College London, London, United Kingdom
Jean Marie Connors
7  Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
Andrea Fontanella
8  Department of Medicine, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy
Gualberto Gussoni
9  Fadoi Research Center, Milan, Italy
Menno V. Huisman
10  Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
Catherine Lambert
11  Division of Hematology, Thrombosis and Hemostasis Unit, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium
Guy Meyer
12  Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
13  Université Paris Descartes, Sorbonne Paris Cité, Paris France
Andres Muñoz
14  Medical Oncology Department, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, Spain
Joaquim Abreu de Sousa
15  Surgical Oncology Department, Institut Português Oncologie, Porto FG, EPE, Porto, Portugal
Adam Torbicki
16  Departments of Pulmonary Hypertension, Thromboembolic Disease and Cardiology, Medical Center for Postgraduate Education, Otwock, Poland
Melina Verso
1  Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
Giorgio Vescovo
17  Internal Medicine, S. Antonio Hospital, Padua, Italy
for the Caravaggio Study Investigators› Institutsangaben
Weitere Informationen


15. Januar 2018

05. Juli 2018

13. August 2018 (online)


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.

Supplementary Material