CARAVAGGIO: Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer

Sponsor

Fadoi Foundation, Italy (Other)

Overall Status

Unknown status

CT.gov ID

NCT03045406

Collaborator

University of Perugia, Italy (Other)

1,168

Enrollment

127

Locations

Arms

31.6

Anticipated Duration (Months)

9.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism	Drug: Apixaban Drug: Dalteparin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1168 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer: A Prospective Randomized Open Blinded End-Point (Probe) Study

Actual Study Start Date :

Apr 13, 2017

Actual Primary Completion Date :

Jun 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apixaban 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 Tablets
Active Comparator: 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	Drug: Dalteparin Injections

Arm

Intervention/Treatment

Experimental: Apixaban

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

Tablets

Active Comparator: 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

Drug: Dalteparin

Injections

Outcome Measures

Primary Outcome Measures

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90089
2	Georgetown University	Washington	District of Columbia	United States	20007
3	University of Florida	Gainesville	Florida	United States	32610
4	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32207
5	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
6	Emory University	Atlanta	Georgia	United States	30322
7	Brigham and Women's Hospital/DFCI	Boston	Massachusetts	United States	02115
8	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	Mayo Clinic	Rochester	Minnesota	United States	55905
11	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
12	Albert Einstein College of Medicine	Bronx	New York	United States	10467
13	New York-Presbyterian Hospital	New York	New York	United States	10021
14	Staten Island University Hospital/Northwell Health	Staten Island	New York	United States	10305
15	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
16	Duke University Medical Center	Durham	North Carolina	United States	27710
17	Ohio State University	Columbus	Ohio	United States	43210
18	University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030
19	Cliniques universitaires Saint-Luc	Brussels		Belgium
20	KU Leuven	Leuven		Belgium
21	Hôpital Privé Arras Les Bonnettes	Arras		France
22	CHU Bordeaux Hôpital Saint André	Bordeaux		France
23	Hopital Cavale Blanche	Brest		France
24	Hôpital des armées HIA Clermont Tonnerre	Brest		France
25	Centre Hospitalier Universitaire de Clermont-Ferrand	Clermont-Ferrand		France
26	Hôpital Louis Mourier	Colombes		France
27	Centre Hospitalier Universitaire Dijon Bourgogne	Dijon		France
28	Centre Hospitalier Universitaire Grenoble Alpes	Grenoble		France
29	CH de Vendée Centre Hospitalier Départemental	La Roche-sur-Yon		France
30	Centre Hospitalier Emile Roux Le Puy-en-Velay	Le Puy-en-Velay		France
31	Université de Limoges	Limoges		France
32	Centre Hospitalier Universitaire Lyon-Sud	Lyon		France
33	Hopital Pasteur - Chu de Nice	Nice		France
34	Hôpital Europeen Georges Pompidou	Paris		France
35	Université Jean Monnet	Saint-Étienne		France
36	Hôpital Sainte Musse	Toulon		France
37	Klinikum Darmstadt	Darmstadt		Germany
38	Städtisches Klinikum Dresden-Friedrichstadt	Dresden		Germany
39	Universitäts GefäßCentrum (UGC)	Dresden		Germany
40	Universitätskrankenhaus Hamburg-Eppendorf	Hamburg		Germany
41	Forschungszentrum Ruhr	Witten		Germany
42	Haemek Medical Center	Afula		Israel
43	Soroka University Medical Center	Be'er Sheva		Israel
44	Rambam Health Care Campus	Haifa		Israel
45	Meir Medical Center	Kfar Saba		Israel
46	Galilee Medical Center	Nahariya		Israel
47	Rabin Medical Center	Petah Tikva		Israel
48	AOU Ospedali Riuniti di Ancona	Ancona		Italy
49	AOSG Moscati	Avellino		Italy
50	Ospedale Sacro Cuore di Gesù Fatebenefratelli	Benevento		Italy
51	ASST Papa Giovanni XXIII	Bergamo		Italy
52	Ospedale Maggiore	Bologna		Italy
53	Ospedale San Giacomo Apostolo	Castelfranco Veneto		Italy
54	Ospedale di Cosenza	Cosenza		Italy
55	Ospedale SS Annunziata	Cuneo		Italy
56	AOU Careggi	Firenze		Italy
57	AOU San Martino	Genova		Italy
58	AOU di Modena	Modena		Italy
59	AO di Rilievo Nazione Antonio Cardarelli	Napoli		Italy
60	Istituto Nazionale Tumori - IRCCS Fondazione Pascale	Napoli		Italy
61	Ospedale Buon Consiglio Fatebenefratelli	Napoli		Italy
62	Ospedale San Martino	Oristano		Italy
63	Azienda Ospedaliera di Padova	Padova		Italy
64	AO Ospedali Riuniti Villa Sofia	Palermo		Italy
65	Department of Internal Medicine - University of Perugia	Perugia		Italy	06129
66	Ospedale SS Cosma e Damiano	Pescia		Italy
67	Ospedale di Piacenza	Piacenza		Italy
68	AOU Pisana	Pisa		Italy
69	Ospedale di Pitigliano	Pitigliano		Italy
70	Ospedale di Ravenna	Ravenna		Italy
71	Arcispedale S. Maria Nuova	Reggio Emilia		Italy
72	Ospedale San Giovanni Calibita Fatebenefratelli	Roma		Italy
73	Policlinico Agostino Gemelli	Roma		Italy
74	Ospedale S. Paolo	Savona		Italy
75	AO Santa Maria	Terni		Italy
76	Ospedale Cà Foncello	Treviso		Italy
77	Ospedale di Udine	Udine		Italy
78	AO Ospedale di Circolo e Fondazione Macchi	Varese		Italy
79	Ospedale Sacro Cuore-Don Calabria di Negrar-Verona.	Verona		Italy
80	Ospedale San Bortolo	Vicenza		Italy
81	Ziekenhuisgroep Twente ZGT	Almelo		Netherlands
82	Academic Medical Centre	Amsterdam		Netherlands
83	Rijnstate Arnhem	Arnhem		Netherlands
84	Rode Kruis Ziekenhuis Beverwijk	Beverwijk		Netherlands
85	Amphia Hospital Breda	Breda		Netherlands
86	Haaglanden Hospital Den Haag	Den Haag		Netherlands
87	Slingeland Doetinchem	Doetinchem		Netherlands
88	Albert Schweitzer ziekenhuis	Dordrecht		Netherlands
89	Medisch Spectrum Twente	Enschede		Netherlands
90	Leiden University Medical Center	Leiden		Netherlands
91	Erasmus MC	Rotterdam		Netherlands
92	HagaZiekenhuis	the Hague		Netherlands
93	Szpital Brzozów	Brzozów		Poland
94	Świetokrzyskie Centrum Onkologii	Kielce		Poland
95	Opolskie Centrum Onkologii	Opole		Poland
96	Medical Centre for Postgraduate Education - ECZ-Otwock	Otwock		Poland	05-400
97	CMKP	Otwock		Poland
98	Wielkoposkie Centrum Onkologii	Poznań		Poland
99	IPO Lisboa	Lisboa		Portugal
100	IPO Porto	Porto		Portugal
101	Tràs-Os Montes e Alto Douro	Vila Real		Portugal
102	Hospital Torrecardenas	Almería		Spain
103	Hospital Sant Pau	Barcelona		Spain
104	Hospital Val d'Hebron	Barcelona		Spain
105	Sabadell Hospital	Barcelona		Spain
106	Fundación Jiménez Díaz	Madrid		Spain
107	Hospital 12 de Octubre	Madrid		Spain
108	Hospital Clara Campal	Madrid		Spain
109	Hospital Clínico San Carlos	Madrid		Spain
110	Hospital Fuenlabrada	Madrid		Spain
111	Hospital General Universitario Gregorio Marañón	Madrid		Spain
112	Hospital Infanta Leonor	Madrid		Spain
113	Hospital La Paz	Madrid		Spain
114	Hospital Puerta de Hierro	Madrid		Spain
115	Hospital Ramón y Cajal	Madrid		Spain
116	Hospital Morales Meseguer	Murcia		Spain
117	Hospital de Málaga	Málaga		Spain
118	Hospital Central de Asturias	Oviedo		Spain
119	Clínica Universitaria de Navarra	Pamplona		Spain
120	Hospital Marqués Valdecilla	Santander		Spain
121	Hospital Virgen del Rocio	Sevilla		Spain
122	Hospital Clínico Lozano Blesa	Zaragoza		Spain
123	University Hospitals Bristol	Bristol		United Kingdom
124	University Hospital of Wales	Cardiff		United Kingdom
125	King's College Hospital	London		United Kingdom
126	Royal Gwent Hospital	Newport		United Kingdom
127	Oxford University Hospital	Oxford		United Kingdom