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› Author Affiliations
Further Information

Publication History

15 January 2018

05 July 2018

Publication Date:
13 August 2018 (eFirst)

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.

Supplementary Material