Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer

Phase 3

• Conditions: Venous Thromboembolism
• Interventions: Drug: Dalteparin; Drug: Apixaban

• Registration Number: NCT03045406
• Lead Sponsor: Fadoi Foundation, Italy

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-01-17
• Study First Submitted QC: 2017-02-03
• Study First Posted: 2017-02-07
• Study Start: 2017-04-13
• Primary Completion: 2019-06-01
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-13
• Last Update Posted: 2019-11-14
• Study Completion: 2019-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1168

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Recurrent venous thromboembolism	6 months	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)

Trial Locations

Locations (127)

University of Southern California; 🇺🇸 Los Angeles, California, United States

Jacksonville Center for Clinical Research; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Dartmouth Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States

New York-Presbyterian Hospital; 🇺🇸 New York, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Staten Island University Hospital/Northwell Health; 🇺🇸 Staten Island, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University of Texas M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Hôpital Privé Arras Les Bonnettes; 🇫🇷 Arras, France

CHU Bordeaux Hôpital Saint André; 🇫🇷 Bordeaux, France

Hopital Cavale Blanche; 🇫🇷 Brest, France

Hôpital des armées HIA Clermont Tonnerre; 🇫🇷 Brest, France

Centre Hospitalier Universitaire de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

Hôpital Louis Mourier; 🇫🇷 Colombes, France

Centre Hospitalier Universitaire Dijon Bourgogne; 🇫🇷 Dijon, France

Centre Hospitalier Universitaire Grenoble Alpes; 🇫🇷 Grenoble, France

Université de Limoges; 🇫🇷 Limoges, France

CH de Vendée Centre Hospitalier Départemental; 🇫🇷 La Roche-sur-Yon, France

Centre Hospitalier Emile Roux Le Puy-en-Velay; 🇫🇷 Le Puy-en-Velay, France

Hopital Pasteur - Chu de Nice; 🇫🇷 Nice, France

Centre Hospitalier Universitaire Lyon-Sud; 🇫🇷 Lyon, France

Hôpital Europeen Georges Pompidou; 🇫🇷 Paris, France

Université Jean Monnet; 🇫🇷 Saint-Étienne, France

Städtisches Klinikum Dresden-Friedrichstadt; 🇩🇪 Dresden, Germany

Universitäts GefäßCentrum (UGC); 🇩🇪 Dresden, Germany

Universitätskrankenhaus Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Forschungszentrum Ruhr; 🇩🇪 Witten, Germany

AOU Ospedali Riuniti di Ancona; 🇮🇹 Ancona, Italy

Ospedale Sacro Cuore di Gesù Fatebenefratelli; 🇮🇹 Benevento, Italy

ASST Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Ospedale San Giacomo Apostolo; 🇮🇹 Castelfranco Veneto, Italy

Ospedale Maggiore; 🇮🇹 Bologna, Italy

Ospedale SS Annunziata; 🇮🇹 Cuneo, Italy

Istituto Nazionale Tumori - IRCCS Fondazione Pascale; 🇮🇹 Napoli, Italy

AOU Careggi; 🇮🇹 Firenze, Italy

AOU San Martino; 🇮🇹 Genova, Italy

AOU di Modena; 🇮🇹 Modena, Italy

AO di Rilievo Nazione Antonio Cardarelli; 🇮🇹 Napoli, Italy

Department of Internal Medicine - University of Perugia; 🇮🇹 Perugia, Italy

Ospedale SS Cosma e Damiano; 🇮🇹 Pescia, Italy

Ospedale di Piacenza; 🇮🇹 Piacenza, Italy

AOU Pisana; 🇮🇹 Pisa, Italy

Ospedale di Pitigliano; 🇮🇹 Pitigliano, Italy

Ospedale di Ravenna; 🇮🇹 Ravenna, Italy

Ospedale San Giovanni Calibita Fatebenefratelli; 🇮🇹 Roma, Italy

Arcispedale S. Maria Nuova; 🇮🇹 Reggio Emilia, Italy

Policlinico Agostino Gemelli; 🇮🇹 Roma, Italy

Ziekenhuisgroep Twente ZGT; 🇳🇱 Almelo, Netherlands

AO Ospedale di Circolo e Fondazione Macchi; 🇮🇹 Varese, Italy

Rijnstate Arnhem; 🇳🇱 Arnhem, Netherlands

Ospedale Sacro Cuore-Don Calabria di Negrar-Verona.; 🇮🇹 Verona, Italy

Amphia Hospital Breda; 🇳🇱 Breda, Netherlands

Tràs-Os Montes e Alto Douro; 🇵🇹 Vila Real, Portugal

Hospital Torrecardenas; 🇪🇸 Almería, Spain

Opolskie Centrum Onkologii; 🇵🇱 Opole, Poland

Wielkoposkie Centrum Onkologii; 🇵🇱 Poznań, Poland

IPO Lisboa; 🇵🇹 Lisboa, Portugal

Hospital Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Val d'Hebron; 🇪🇸 Barcelona, Spain

Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Sabadell Hospital; 🇪🇸 Barcelona, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Hospital Clara Campal; 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Fuenlabrada; 🇪🇸 Madrid, Spain

Hospital La Paz; 🇪🇸 Madrid, Spain

Hospital Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Puerta de Hierro; 🇪🇸 Madrid, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital de Málaga; 🇪🇸 Málaga, Spain

Hospital Morales Meseguer; 🇪🇸 Murcia, Spain

Hospital Central de Asturias; 🇪🇸 Oviedo, Spain

University Hospitals Bristol; 🇬🇧 Bristol, United Kingdom

Hospital Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital Clínico Lozano Blesa; 🇪🇸 Zaragoza, Spain

Clínica Universitaria de Navarra; 🇪🇸 Pamplona, Spain

Hospital Marqués Valdecilla; 🇪🇸 Santander, Spain

University Hospital of Wales; 🇬🇧 Cardiff, United Kingdom

Royal Gwent Hospital; 🇬🇧 Newport, United Kingdom

King's College Hospital; 🇬🇧 London, United Kingdom

Oxford University Hospital; 🇬🇧 Oxford, United Kingdom

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

University of Florida; 🇺🇸 Gainesville, Florida, United States

KU Leuven; 🇧🇪 Leuven, Belgium

Albert Schweitzer ziekenhuis; 🇳🇱 Dordrecht, Netherlands

Szpital Brzozów; 🇵🇱 Brzozów, Poland

Brigham and Women's Hospital/DFCI; 🇺🇸 Boston, Massachusetts, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Rode Kruis Ziekenhuis Beverwijk; 🇳🇱 Beverwijk, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

HagaZiekenhuis; 🇳🇱 the Hague, Netherlands

Galilee Medical Center; 🇮🇱 Nahariya, Israel

Academic Medical Centre; 🇳🇱 Amsterdam, Netherlands

Medisch Spectrum Twente; 🇳🇱 Enschede, Netherlands

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Soroka University Medical Center; 🇮🇱 Be'er Sheva, Israel

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Haemek Medical Center; 🇮🇱 Afula, Israel

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Haaglanden Hospital Den Haag; 🇳🇱 Den Haag, Netherlands

Slingeland Doetinchem; 🇳🇱 Doetinchem, Netherlands

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Świetokrzyskie Centrum Onkologii; 🇵🇱 Kielce, Poland

Medical Centre for Postgraduate Education - ECZ-Otwock; 🇵🇱 Otwock, Poland

CMKP; 🇵🇱 Otwock, Poland

IPO Porto; 🇵🇹 Porto, Portugal

Ospedale di Cosenza; 🇮🇹 Cosenza, Italy

AOSG Moscati; 🇮🇹 Avellino, Italy

Ospedale Buon Consiglio Fatebenefratelli; 🇮🇹 Napoli, Italy

Ospedale San Martino; 🇮🇹 Oristano, Italy

Azienda Ospedaliera di Padova; 🇮🇹 Padova, Italy

AO Ospedali Riuniti Villa Sofia; 🇮🇹 Palermo, Italy

Ospedale S. Paolo; 🇮🇹 Savona, Italy

AO Santa Maria; 🇮🇹 Terni, Italy

Ospedale Cà Foncello; 🇮🇹 Treviso, Italy

Ospedale di Udine; 🇮🇹 Udine, Italy

Ospedale San Bortolo; 🇮🇹 Vicenza, Italy

Hôpital Sainte Musse; 🇫🇷 Toulon, France

Klinikum Darmstadt; 🇩🇪 Darmstadt, Germany