Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer

NCT ID: NCT03045406

Last Updated: 2025-06-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-13

Study Completion Date

2019-12-01

Brief Summary

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Apixaban for the treatment of venous thromboembolism in patients with cancer: a prospective randomized open blinded end-point (PROBE) study

Detailed Description

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Conditions

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Venous Thromboembolism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Apixaban

orally administered, at the dose of 10 mg bid for 7 days, followed by 5 mg bid (total period of treatment: six months)

Group Type EXPERIMENTAL

Apixaban

Intervention Type DRUG

Tablets

Dalteparin

subcutaneously administered, at a dose of 200 IU/kg SC o.i.d for 1 month. Thereafter, dalteparin will be administered at a dose of 150 IU/kg o.i.d. for 5 months

Group Type ACTIVE_COMPARATOR

Dalteparin

Intervention Type DRUG

Injections

Interventions

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Apixaban

Tablets

Intervention Type DRUG

Dalteparin

Injections

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Consecutive patients with a newly diagnosed, objectively confirmed: symptomatic or unsuspected, proximal lower-limb DVT or symptomatic PE or unsuspected PE in a segmental or more proximal pulmonary artery;
* Any type of cancer (other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumor or intracerebral metastasis and acute leukemia);
* Signed and dated informed consent of the patient, available before the start of any specific trial procedure.

Exclusion Criteria

* age \<18 years;
* ECOG Performance Status III or IV;
* life expectancy of less than 6 months;

Related to anticoagulant treatment:

* administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization;
* 3 or more doses of a vitamin K antagonist before randomization;
* thrombectomy, vena cava filter insertion, or thrombolysis used to manage the index episode;
* indication for anticoagulant treatment for a disease other than the index VTE episode;

Related to bleeding risk:

* thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin over 165 mg daily or dual antiplatelet therapy;
* active bleeding or a high risk of bleeding contraindicating anticoagulant treatment;
* recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery
* hemoglobin level lower than 8 g/dL (5.0 mmol/L) or platelet count \<75x10\^9/L or history of heparin induced thrombocytopenia;
* creatinine clearance \< 30 ml /min based on the Cockcroft Gault equation;
* acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and/or bilirubin level 2 times or more higher the upper limit of the normal range;
* uncontrolled hypertension (systolic BP\> 180 mmHg or diastolic BP \> 100 mmHg despite antihypertensive treatment);
* concomitant use of strong inhibitors or inducers of both cytochrome P-450 3A4 and P-Glycoprotein;

Standard criteria:

* bacterial endocarditis;
* hypersensitivity to the active substance or to any of the excipients of study drug;
* patients participation in other pharmaco therapeutic program with an experimental therapy that is known to effect the coagulation system;
* childbearing potential without proper contraceptive measures, pregnancy, or breast feeding;
* any condition that as judged by the Investigator would place the subject at increased risk of harm if he/she participated in the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Of Perugia

OTHER

Sponsor Role collaborator

Fadoi Foundation, Italy

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gualberto Gussoni, MD

Role: STUDY_DIRECTOR

FADOI Foundation

Locations

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University of Southern California

Los Angeles, California, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Brigham and Women's Hospital/DFCI

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

New York-Presbyterian Hospital

New York, New York, United States

Site Status

Staten Island University Hospital/Northwell Health

Staten Island, New York, United States

Site Status

Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Site Status

KU Leuven

Leuven, , Belgium

Site Status

Hôpital Privé Arras Les Bonnettes

Arras, , France

Site Status

CHU Bordeaux Hôpital Saint André

Bordeaux, , France

Site Status

Hopital Cavale Blanche

Brest, , France

Site Status

Hôpital des armées HIA Clermont Tonnerre

Brest, , France

Site Status

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

Hôpital Louis Mourier

Colombes, , France

Site Status

Centre Hospitalier Universitaire Dijon Bourgogne

Dijon, , France

Site Status

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, , France

Site Status

CH de Vendée Centre Hospitalier Départemental

La Roche-sur-Yon, , France

Site Status

Centre Hospitalier Emile Roux Le Puy-en-Velay

Le Puy-en-Velay, , France

Site Status

Université de Limoges

Limoges, , France

Site Status

Centre Hospitalier Universitaire Lyon-Sud

Lyon, , France

Site Status

Hopital Pasteur - Chu de Nice

Nice, , France

Site Status

Hôpital Europeen Georges Pompidou

Paris, , France

Site Status

Université Jean Monnet

Saint-Etienne, , France

Site Status

Hôpital Sainte Musse

Toulon, , France

Site Status

Klinikum Darmstadt

Darmstadt, , Germany

Site Status

Städtisches Klinikum Dresden-Friedrichstadt

Dresden, , Germany

Site Status

Universitäts GefäßCentrum (UGC)

Dresden, , Germany

Site Status

Universitätskrankenhaus Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Forschungszentrum Ruhr

Witten, , Germany

Site Status

Haemek Medical Center

Afula, , Israel

Site Status

Soroka University Medical Center

Beersheba, , Israel

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Meir Medical Center

Kfar Saba, , Israel

Site Status

Galilee Medical Center

Nahariya, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

AOU Ospedali Riuniti di Ancona

Ancona, , Italy

Site Status

AOSG Moscati

Avellino, , Italy

Site Status

Ospedale Sacro Cuore di Gesù Fatebenefratelli

Benevento, , Italy

Site Status

ASST Papa Giovanni XXIII

Bergamo, , Italy

Site Status

Ospedale Maggiore

Bologna, , Italy

Site Status

Ospedale San Giacomo Apostolo

Castelfranco Veneto, , Italy

Site Status

Ospedale di Cosenza

Cosenza, , Italy

Site Status

Ospedale SS Annunziata

Cuneo, , Italy

Site Status

AOU Careggi

Florence, , Italy

Site Status

AOU San Martino

Genova, , Italy

Site Status

AOU di Modena

Modena, , Italy

Site Status

AO di Rilievo Nazione Antonio Cardarelli

Napoli, , Italy

Site Status

Istituto Nazionale Tumori - IRCCS Fondazione Pascale

Napoli, , Italy

Site Status

Ospedale Buon Consiglio Fatebenefratelli

Napoli, , Italy

Site Status

Ospedale San Martino

Oristano, , Italy

Site Status

Azienda Ospedaliera di Padova

Padua, , Italy

Site Status

AO Ospedali Riuniti Villa Sofia

Palermo, , Italy

Site Status

Department of Internal Medicine - University of Perugia

Perugia, , Italy

Site Status

Ospedale SS Cosma e Damiano

Pescia, , Italy

Site Status

Ospedale di Piacenza

Piacenza, , Italy

Site Status

AOU Pisana

Pisa, , Italy

Site Status

Ospedale di Pitigliano

Pitigliano, , Italy

Site Status

Ospedale di Ravenna

Ravenna, , Italy

Site Status

Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Site Status

Ospedale San Giovanni Calibita Fatebenefratelli

Roma, , Italy

Site Status

Policlinico Agostino Gemelli

Roma, , Italy

Site Status

Ospedale S. Paolo

Savona, , Italy

Site Status

AO Santa Maria

Terni, , Italy

Site Status

Ospedale Cà Foncello

Treviso, , Italy

Site Status

Ospedale di Udine

Udine, , Italy

Site Status

AO Ospedale di Circolo e Fondazione Macchi

Varese, , Italy

Site Status

Ospedale Sacro Cuore-Don Calabria di Negrar-Verona.

Verona, , Italy

Site Status

Ospedale San Bortolo

Vicenza, , Italy

Site Status

Ziekenhuisgroep Twente ZGT

Almelo, , Netherlands

Site Status

Academic Medical Centre

Amsterdam, , Netherlands

Site Status

Rijnstate Arnhem

Arnhem, , Netherlands

Site Status

Rode Kruis Ziekenhuis Beverwijk

Beverwijk, , Netherlands

Site Status

Amphia Hospital Breda

Breda, , Netherlands

Site Status

Slingeland Doetinchem

Doetinchem, , Netherlands

Site Status

Albert Schweitzer ziekenhuis

Dordrecht, , Netherlands

Site Status

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

Haaglanden Hospital Den Haag

The Hague, , Netherlands

Site Status

HagaZiekenhuis

The Hague, , Netherlands

Site Status

Szpital Brzozów

Brzozów, , Poland

Site Status

Świetokrzyskie Centrum Onkologii

Kielce, , Poland

Site Status

Opolskie Centrum Onkologii

Opole, , Poland

Site Status

Medical Centre for Postgraduate Education - ECZ-Otwock

Otwock, , Poland

Site Status

CMKP

Otwock, , Poland

Site Status

Wielkoposkie Centrum Onkologii

Poznan, , Poland

Site Status

IPO Lisboa

Lisbon, , Portugal

Site Status

IPO Porto

Porto, , Portugal

Site Status

Tràs-Os Montes e Alto Douro

Vila Real, , Portugal

Site Status

Hospital Torrecardenas

Almería, , Spain

Site Status

Hospital Sant Pau

Barcelona, , Spain

Site Status

Hospital Val d'Hebron

Barcelona, , Spain

Site Status

Sabadell Hospital

Barcelona, , Spain

Site Status

Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Hospital 12 de Octubre

Madrid, , Spain

Site Status

Hospital Clara Campal

Madrid, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Fuenlabrada

Madrid, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Infanta Leonor

Madrid, , Spain

Site Status

Hospital La Paz

Madrid, , Spain

Site Status

Hospital Puerta de Hierro

Madrid, , Spain

Site Status

Hospital Ramón y Cajal

Madrid, , Spain

Site Status

Hospital de Málaga

Málaga, , Spain

Site Status

Hospital Morales Meseguer

Murcia, , Spain

Site Status

Hospital Central de Asturias

Oviedo, , Spain

Site Status

Clínica Universitaria de Navarra

Pamplona, , Spain

Site Status

Hospital Marqués Valdecilla

Santander, , Spain

Site Status

Hospital Virgen del Rocio

Seville, , Spain

Site Status

Hospital Clínico Lozano Blesa

Zaragoza, , Spain

Site Status

University Hospitals Bristol

Bristol, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Royal Gwent Hospital

Newport, , United Kingdom

Site Status

Oxford University Hospital

Oxford, , United Kingdom

Site Status

Countries

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United States Belgium France Germany Israel Italy Netherlands Poland Portugal Spain United Kingdom

References

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Becattini C, Bauersachs R, Maraziti G, Bertoletti L, Cohen A, Connors JM, Manfellotto D, Sanchez A, Brenner B, Agnelli G. Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial. Haematologica. 2022 Jul 1;107(7):1567-1576. doi: 10.3324/haematol.2021.279072.

Reference Type DERIVED
PMID: 34382385 (View on PubMed)

Giustozzi M, Connors JM, Ruperez Blanco AB, Szmit S, Falvo N, Cohen AT, Huisman M, Bauersachs R, Dentali F, Becattini C, Agnelli G. Clinical characteristics and outcomes of incidental venous thromboembolism in cancer patients: Insights from the Caravaggio study. J Thromb Haemost. 2021 Nov;19(11):2751-2759. doi: 10.1111/jth.15461. Epub 2021 Jul 29.

Reference Type DERIVED
PMID: 34260816 (View on PubMed)

Agnelli G, Becattini C, Meyer G, Munoz A, Huisman MV, Connors JM, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro MR, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M; Caravaggio Investigators. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. doi: 10.1056/NEJMoa1915103. Epub 2020 Mar 29.

Reference Type DERIVED
PMID: 32223112 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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FADOI.03.2016

Identifier Type: -

Identifier Source: org_study_id

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