Clinical trial NCT03045406: Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer
Official title: Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer: A Prospective Randomized Open Blinded End-Point (Probe) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Lead sponsor: Fadoi Foundation, Italy
Sponsor class: OTHER
Collaborators: name: University Of Perugia
First posted: 2017-02-07
Enrollment: 1170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Recurrent Venous Thromboembolism
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital/DFCI
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: New York-Presbyterian Hospital
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital/Northwell Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Leuven
country: Belgium
facility: KU Leuven
city: Arras
country: France
facility: Hôpital Privé Arras Les Bonnettes
city: Bordeaux
country: France
facility: CHU Bordeaux Hôpital Saint André
city: Brest
country: France
facility: Hopital Cavale Blanche
city: Brest
country: France
facility: Hôpital des armées HIA Clermont Tonnerre
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes
city: La Roche-sur-Yon
country: France
facility: CH de Vendée Centre Hospitalier Départemental
city: Le Puy-en-Velay
country: France
facility: Centre Hospitalier Emile Roux Le Puy-en-Velay
city: Limoges
country: France
facility: Université de Limoges
city: Lyon
country: France
facility: Centre Hospitalier Universitaire Lyon-Sud
city: Nice
country: France
facility: Hopital Pasteur - Chu de Nice
city: Paris
country: France
facility: Hôpital Europeen Georges Pompidou
city: Saint-Étienne
country: France
facility: Université Jean Monnet
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dresden
country: Germany
facility: Städtisches Klinikum Dresden-Friedrichstadt
city: Dresden
country: Germany
facility: Universitäts GefäßCentrum (UGC)
city: Hamburg
country: Germany
facility: Universitätskrankenhaus Hamburg-Eppendorf
city: Witten
country: Germany
facility: Forschungszentrum Ruhr
city: Afula
country: Israel
facility: Haemek Medical Center
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti di Ancona
city: Avellino
country: Italy
facility: AOSG Moscati
city: Benevento
country: Italy
facility: Ospedale Sacro Cuore di Gesù Fatebenefratelli
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Ospedale Maggiore
city: Castelfranco Veneto
country: Italy
facility: Ospedale San Giacomo Apostolo
city: Cosenza
country: Italy
facility: Ospedale di Cosenza
city: Cuneo
country: Italy
facility: Ospedale SS Annunziata
city: Firenze
country: Italy
facility: AOU Careggi
city: Genova
country: Italy
facility: AOU San Martino
city: Modena
country: Italy
facility: AOU di Modena
city: Napoli
country: Italy
facility: AO di Rilievo Nazione Antonio Cardarelli
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - IRCCS Fondazione Pascale
city: Napoli
country: Italy
facility: Ospedale Buon Consiglio Fatebenefratelli
city: Oristano
country: Italy
facility: Ospedale San Martino
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: AO Ospedali Riuniti Villa Sofia
city: Perugia
country: Italy
facility: Department of Internal Medicine - University of Perugia
city: Pescia
country: Italy
facility: Ospedale SS Cosma e Damiano
city: Piacenza
country: Italy
facility: Ospedale di Piacenza
city: Pisa
country: Italy
facility: AOU Pisana
city: Pitigliano
country: Italy
facility: Ospedale di Pitigliano
city: Ravenna
country: Italy
facility: Ospedale di Ravenna
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Roma
country: Italy
facility: Ospedale San Giovanni Calibita Fatebenefratelli
city: Roma
country: Italy
facility: Policlinico Agostino Gemelli
city: Savona
country: Italy
facility: Ospedale S. Paolo
city: Terni
country: Italy
facility: AO Santa Maria
city: Treviso
country: Italy
facility: Ospedale Cà Foncello
city: Udine
country: Italy
facility: Ospedale di Udine
city: Varese
country: Italy
facility: AO Ospedale di Circolo e Fondazione Macchi
city: Verona
country: Italy
facility: Ospedale Sacro Cuore-Don Calabria di Negrar-Verona.
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente ZGT
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre
city: Arnhem
country: Netherlands
facility: Rijnstate Arnhem
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis Beverwijk
city: Breda
country: Netherlands
facility: Amphia Hospital Breda
city: Den Haag
country: Netherlands
facility: Haaglanden Hospital Den Haag
city: Doetinchem
country: Netherlands
facility: Slingeland Doetinchem
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: the Hague
country: Netherlands
facility: HagaZiekenhuis
city: Brzozów
country: Poland
facility: Szpital Brzozów
city: Kielce
country: Poland
facility: Świetokrzyskie Centrum Onkologii
city: Opole
country: Poland
facility: Opolskie Centrum Onkologii
city: Otwock
country: Poland
facility: Medical Centre for Postgraduate Education - ECZ-Otwock
city: Otwock
country: Poland
facility: CMKP
city: Poznań
country: Poland
facility: Wielkoposkie Centrum Onkologii
city: Lisboa
country: Portugal
facility: IPO Lisboa
city: Porto
country: Portugal
facility: IPO Porto
city: Vila Real
country: Portugal
facility: Tràs-Os Montes e Alto Douro
city: Almería
country: Spain
facility: Hospital Torrecardenas
city: Barcelona
country: Spain
facility: Hospital Sant Pau
city: Barcelona
country: Spain
facility: Hospital Val d'Hebron
city: Barcelona
country: Spain
facility: Sabadell Hospital
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Clara Campal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Fuenlabrada
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Málaga
country: Spain
facility: Hospital de Málaga
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
city: Santander
country: Spain
facility: Hospital Marqués Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Zaragoza
country: Spain
facility: Hospital Clínico Lozano Blesa
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: King's College Hospital
city: Newport
country: United Kingdom
facility: Royal Gwent Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospital
Study officials:
affiliation: FADOI Foundation
name: Gualberto Gussoni, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.