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

• ClinicalTrials.gov Identifier: NCT03045406
• Recruitment Status: Unknown
• First Posted: February 7, 2017
• Last Update Posted: November 14, 2019
• Sponsor: Fadoi Foundation, Italy
• Collaborator: University Of Perugia
• Information provided by (Responsible Party): Fadoi Foundation, Italy

Tracking Information

• First Submitted Date: January 17, 2017
• First Posted Date: February 7, 2017
• Last Update Posted Date: November 14, 2019
• Actual Study Start Date: April 13, 2017
• Actual Primary Completion Date: June 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2017)

Recurrent venous thromboembolism [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Venous Thromboembolism

Intervention

• Drug: Apixaban
  Tablets
• Drug: Dalteparin
  Injections

Study Arms

• 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)
  Intervention: Drug: Apixaban
• 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
  Intervention: Drug: Dalteparin

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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: February 3, 2017): 1168
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2019
• Actual Primary Completion Date: June 1, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany, Israel, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03045406
• Other Study ID Numbers: FADOI.03.2016
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fadoi Foundation, Italy
• Original Responsible Party: Same as current
• Current Study Sponsor: Fadoi Foundation, Italy
• Original Study Sponsor: Same as current
• Collaborators: University Of Perugia

Investigators

• Study Director: Gualberto Gussoni, MD; FADOI Foundation

• PRS Account: Fadoi Foundation, Italy
• Verification Date: November 2019