NCT03045406

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,170

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Apr 2017

Typical duration for phase_3

Geographic Reach
11 countries

127 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 17, 2017

Completed
21 days until next milestone

First Posted

Study publicly available on registry

February 7, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

April 13, 2017

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2019

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
5.6 years until next milestone

Results Posted

Study results publicly available

June 18, 2025

Completed
Last Updated

June 24, 2025

Status Verified

June 1, 2025

Enrollment Period

2.1 years

First QC Date

January 17, 2017

Results QC Date

February 6, 2025

Last Update Submit

June 20, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Recurrent Venous Thromboembolism

    Primary efficacy outcome: objectively confirmed recurrent VTE occurring during the study period, that means the composite of: · proximal DVT of the lower limbs (symptomatic or unsuspected), DVT of the upper limb (symptomatic), PE (symptomatic or unsuspected)

    6 months

Study Arms (2)

Apixaban

EXPERIMENTAL

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

Drug: Apixaban

Dalteparin

ACTIVE COMPARATOR

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

Drug: Dalteparin

Interventions

Tablets

Apixaban

Injections

Dalteparin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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;
  • 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;
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (127)

University of Southern California

Los Angeles, California, 90089, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Brigham and Women's Hospital/DFCI

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

New York-Presbyterian Hospital

New York, New York, 10021, United States

Location

Staten Island University Hospital/Northwell Health

Staten Island, New York, 10305, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cliniques universitaires Saint-Luc

Brussels, Belgium

Location

KU Leuven

Leuven, Belgium

Location

Hôpital Privé Arras Les Bonnettes

Arras, France

Location

CHU Bordeaux Hôpital Saint André

Bordeaux, France

Location

Hopital Cavale Blanche

Brest, France

Location

Hôpital des armées HIA Clermont Tonnerre

Brest, France

Location

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, France

Location

Hôpital Louis Mourier

Colombes, France

Location

Centre Hospitalier Universitaire Dijon Bourgogne

Dijon, France

Location

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, France

Location

CH de Vendée Centre Hospitalier Départemental

La Roche-sur-Yon, France

Location

Centre Hospitalier Emile Roux Le Puy-en-Velay

Le Puy-en-Velay, France

Location

Université de Limoges

Limoges, France

Location

Centre Hospitalier Universitaire Lyon-Sud

Lyon, France

Location

Hopital Pasteur - Chu de Nice

Nice, France

Location

Hôpital Europeen Georges Pompidou

Paris, France

Location

Université Jean Monnet

Saint-Etienne, France

Location

Hôpital Sainte Musse

Toulon, France

Location

Klinikum Darmstadt

Darmstadt, Germany

Location

Städtisches Klinikum Dresden-Friedrichstadt

Dresden, Germany

Location

Universitäts GefäßCentrum (UGC)

Dresden, Germany

Location

Universitätskrankenhaus Hamburg-Eppendorf

Hamburg, Germany

Location

Forschungszentrum Ruhr

Witten, Germany

Location

Haemek Medical Center

Afula, Israel

Location

Soroka University Medical Center

Beersheba, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Galilee Medical Center

Nahariya, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

AOU Ospedali Riuniti di Ancona

Ancona, Italy

Location

AOSG Moscati

Avellino, Italy

Location

Ospedale Sacro Cuore di Gesù Fatebenefratelli

Benevento, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, Italy

Location

Ospedale Maggiore

Bologna, Italy

Location

Ospedale San Giacomo Apostolo

Castelfranco Veneto, Italy

Location

Ospedale di Cosenza

Cosenza, Italy

Location

Ospedale SS Annunziata

Cuneo, Italy

Location

AOU Careggi

Florence, Italy

Location

AOU San Martino

Genova, Italy

Location

AOU di Modena

Modena, Italy

Location

AO di Rilievo Nazione Antonio Cardarelli

Napoli, Italy

Location

Istituto Nazionale Tumori - IRCCS Fondazione Pascale

Napoli, Italy

Location

Ospedale Buon Consiglio Fatebenefratelli

Napoli, Italy

Location

Ospedale San Martino

Oristano, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

AO Ospedali Riuniti Villa Sofia

Palermo, Italy

Location

Department of Internal Medicine - University of Perugia

Perugia, 06129, Italy

Location

Ospedale SS Cosma e Damiano

Pescia, Italy

Location

Ospedale di Piacenza

Piacenza, Italy

Location

AOU Pisana

Pisa, Italy

Location

Ospedale di Pitigliano

Pitigliano, Italy

Location

Ospedale di Ravenna

Ravenna, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

Ospedale San Giovanni Calibita Fatebenefratelli

Roma, Italy

Location

Policlinico Agostino Gemelli

Roma, Italy

Location

Ospedale S. Paolo

Savona, Italy

Location

AO Santa Maria

Terni, Italy

Location

Ospedale Cà Foncello

Treviso, Italy

Location

Ospedale di Udine

Udine, Italy

Location

AO Ospedale di Circolo e Fondazione Macchi

Varese, Italy

Location

Ospedale Sacro Cuore-Don Calabria di Negrar-Verona.

Verona, Italy

Location

Ospedale San Bortolo

Vicenza, Italy

Location

Ziekenhuisgroep Twente ZGT

Almelo, Netherlands

Location

Academic Medical Centre

Amsterdam, Netherlands

Location

Rijnstate Arnhem

Arnhem, Netherlands

Location

Rode Kruis Ziekenhuis Beverwijk

Beverwijk, Netherlands

Location

Amphia Hospital Breda

Breda, Netherlands

Location

Slingeland Doetinchem

Doetinchem, Netherlands

Location

Albert Schweitzer ziekenhuis

Dordrecht, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Haaglanden Hospital Den Haag

The Hague, Netherlands

Location

HagaZiekenhuis

The Hague, Netherlands

Location

Szpital Brzozów

Brzozów, Poland

Location

Świetokrzyskie Centrum Onkologii

Kielce, Poland

Location

Opolskie Centrum Onkologii

Opole, Poland

Location

Medical Centre for Postgraduate Education - ECZ-Otwock

Otwock, 05-400, Poland

Location

CMKP

Otwock, Poland

Location

Wielkoposkie Centrum Onkologii

Poznan, Poland

Location

IPO Lisboa

Lisbon, Portugal

Location

IPO Porto

Porto, Portugal

Location

Tràs-Os Montes e Alto Douro

Vila Real, Portugal

Location

Hospital Torrecardenas

Almería, Spain

Location

Hospital Sant Pau

Barcelona, Spain

Location

Hospital Val d'Hebron

Barcelona, Spain

Location

Sabadell Hospital

Barcelona, Spain

Location

Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Clara Campal

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Fuenlabrada

Madrid, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Infanta Leonor

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital de Málaga

Málaga, Spain

Location

Hospital Morales Meseguer

Murcia, Spain

Location

Hospital Central de Asturias

Oviedo, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Spain

Location

Hospital Marqués Valdecilla

Santander, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Hospital Clínico Lozano Blesa

Zaragoza, Spain

Location

University Hospitals Bristol

Bristol, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Royal Gwent Hospital

Newport, United Kingdom

Location

Oxford University Hospital

Oxford, United Kingdom

Location

Related Publications (3)

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

apixabanDalteparin

Condition Hierarchy (Ancestors)

ThromboembolismEmbolism and ThrombosisVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-WeightHeparinGlycosaminoglycansPolysaccharidesCarbohydrates

Results Point of Contact

Title
Giorgio Vescovo
Organization
FadoiFoundation

Study Officials

  • Gualberto Gussoni, MD

    FADOI Foundation

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2017

First Posted

February 7, 2017

Study Start

April 13, 2017

Primary Completion

June 1, 2019

Study Completion

December 1, 2019

Last Updated

June 24, 2025

Results First Posted

June 18, 2025

Record last verified: 2025-06

Locations