Venous ThromboembolismPhase 3CARAVAGGIONCT03045406
Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer
A Phase 3 study testing Apixaban and Dalteparin in people with Venous Thromboembolism, run by Fadoi Foundation, Italy at 127 sites in 11 countries.
Trial summary
Apixaban for the treatment of venous thromboembolism in patients with cancer: a prospective randomized open blinded end-point (PROBE) study Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Apixaban and Dalteparin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,170 participants
- Where
- 127 sitesin 11 countries
- Study dates
- 13 Apr 2017to 1 Dec 2019
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
127 sites in 11 countries.
127 sites in 11 countries
Italy33 sites
AOU Ospedali Riuniti di Ancona
Ancona
AOSG Moscati
Avellino
Ospedale Sacro Cuore di Gesù Fatebenefratelli
Benevento
ASST Papa Giovanni XXIII
Bergamo
Ospedale Maggiore
Bologna
Ospedale San Giacomo Apostolo
Castelfranco Veneto
Ospedale di Cosenza
Cosenza
Ospedale SS Annunziata
Cuneo
AOU Careggi
Florence
AOU San Martino
Genova
AOU di Modena
Modena
AO di Rilievo Nazione Antonio Cardarelli
Naples
Istituto Nazionale Tumori - IRCCS Fondazione Pascale
Naples
Ospedale Buon Consiglio Fatebenefratelli
Naples
Ospedale San Martino
Oristano
Azienda Ospedaliera di Padova
Padova
AO Ospedali Riuniti Villa Sofia
Palermo
Department of Internal Medicine - University of Perugia
Perugia, 06129
Ospedale SS Cosma e Damiano
Pescia
Ospedale di Piacenza
Piacenza
AOU Pisana
Pisa
Ospedale di Pitigliano
Pitigliano
Ospedale di Ravenna
Ravenna
Arcispedale S. Maria Nuova
Reggio Emilia
Ospedale San Giovanni Calibita Fatebenefratelli
Roma
Policlinico Agostino Gemelli
Roma
Ospedale S. Paolo
Savona
AO Santa Maria
Terni
Ospedale Cà Foncello
Treviso
Ospedale di Udine
Udine
AO Ospedale di Circolo e Fondazione Macchi
Varese
Ospedale Sacro Cuore-Don Calabria di Negrar-Verona.
Verona
Ospedale San Bortolo
Vicenza
Spain21 sites
Hospital Torrecardenas
Almería
Hospital Sant Pau
Barcelona
Hospital Val d'Hebron
Barcelona
Sabadell Hospital
Barcelona
Fundación Jiménez Díaz
Madrid
Hospital 12 de Octubre
Madrid
Hospital Clara Campal
Madrid
Hospital Clínico San Carlos
Madrid
Hospital Fuenlabrada
Madrid
Hospital General Universitario Gregorio Marañón
Madrid
Hospital Infanta Leonor
Madrid
Hospital La Paz
Madrid
Hospital Puerta de Hierro
Madrid
Hospital Ramón y Cajal
Madrid
Hospital de Málaga
Málaga
Hospital Morales Meseguer
Murcia
Hospital Central de Asturias
Oviedo
Clínica Universitaria de Navarra
Pamplona
Hospital Marqués Valdecilla
Santander
Hospital Virgen del Rocio
Seville
Hospital Clínico Lozano Blesa
Zaragoza
United States18 sites
Emory University
Atlanta, Georgia, 30322
Brigham and Women's Hospital/DFCI
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Ohio State University
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32207
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Southern California
Los Angeles, California, 90089
New York-Presbyterian Hospital
New York, New York, 10021
Mayo Clinic
Rochester, Minnesota, 55905
Staten Island University Hospital/Northwell Health
Staten Island, New York, 10305
Albert Einstein College of Medicine
The Bronx, New York, 10467
Georgetown University
Washington D.C., District of Columbia, 20007
France16 sites
Hôpital Privé Arras Les Bonnettes
Arras
CHU Bordeaux Hôpital Saint André
Bordeaux
Hopital Cavale Blanche
Brest
Hôpital des armées HIA Clermont Tonnerre
Brest
Centre Hospitalier Universitaire de Clermont-Ferrand
Clermont-Ferrand
Hôpital Louis Mourier
Colombes
Centre Hospitalier Universitaire Dijon Bourgogne
Dijon
Centre Hospitalier Universitaire Grenoble Alpes
Grenoble
CH de Vendée Centre Hospitalier Départemental
La Roche-sur-Yon
Centre Hospitalier Emile Roux Le Puy-en-Velay
Le Puy-en-Velay
Université de Limoges
Limoges
Centre Hospitalier Universitaire Lyon-Sud
Lyon
Hopital Pasteur - Chu de Nice
Nice
Hôpital Europeen Georges Pompidou
Paris
Université Jean Monnet
Saint-Etienne
Hôpital Sainte Musse
Toulon
Netherlands12 sites
Ziekenhuisgroep Twente ZGT
Almelo
Academic Medical Centre
Amsterdam
Rijnstate Arnhem
Arnhem
Rode Kruis Ziekenhuis Beverwijk
Beverwijk
Amphia Hospital Breda
Breda
Slingeland Doetinchem
Doetinchem
Albert Schweitzer ziekenhuis
Dordrecht
Medisch Spectrum Twente
Enschede
Leiden University Medical Center
Leiden
Erasmus MC
Rotterdam
Haaglanden Hospital Den Haag
The Hague
HagaZiekenhuis
The Hague
Israel6 sites
Haemek Medical Center
Afula
Soroka University Medical Center
Beersheba
Rambam Health Care Campus
Haifa
Meir Medical Center
Kfar Saba
Galilee Medical Center
Nahariya
Rabin Medical Center
Petah Tikva
Poland6 sites
Szpital Brzozów
Brzozów
Świetokrzyskie Centrum Onkologii
Kielce
Opolskie Centrum Onkologii
Opole
Medical Centre for Postgraduate Education - ECZ-Otwock
Otwock, 05-400
CMKP
Otwock
Wielkoposkie Centrum Onkologii
Poznan
Germany5 sites
Klinikum Darmstadt
Darmstadt
Städtisches Klinikum Dresden-Friedrichstadt
Dresden
Universitäts GefäßCentrum (UGC)
Dresden
Universitätskrankenhaus Hamburg-Eppendorf
Hamburg
Forschungszentrum Ruhr
Witten
United Kingdom5 sites
University Hospitals Bristol
Bristol
University Hospital of Wales
Cardiff
King's College Hospital
London
Royal Gwent Hospital
Newport
Oxford University Hospital
Oxford
Portugal3 sites
IPO Lisboa
Lisbon
IPO Porto
Porto
Tràs-Os Montes e Alto Douro
Vila Real
About this study
Official title: Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer: A Prospective Randomized Open Blinded End-Point (Probe) Study
Apixaban for the treatment of venous thromboembolism in patients with cancer: a prospective randomized open blinded end-point (PROBE) study
- Conditions
- Venous Thromboembolism
- Being tested
- Apixaban, Dalteparin
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Tablets
DalteparinDrug
Injections
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Drug: Dalteparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2017 (estimated)
- Study start13 Apr 2017
- Primary completion1 Jun 2019
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fadoi Foundation, Italy
- Sponsor type
- University, hospital or other
- Collaborators
- University Of Perugia
- Responsible party
- Sponsor
- Investigators
- Gualberto Gussoni, MD, Study director, FADOI Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03045406
- Sponsor's protocol ID
- FADOI.03.2016
- Acronym
- CARAVAGGIO
- Status last verified
- Jun 2025
- First submitted
- 17 Jan 2017
- Last updated
- 24 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34382385Giustozzi 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.
PubMed 34260816Agnelli 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.
PubMed 32223112