Apixaban for the treatment of venous thromboembolism in patients with cancer
- Conditions
- Venous thromboembolism in cancer patientsMedDRA version: 21.1Level: LLTClassification code 10066899Term: Venous thromboembolismSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2016-003093-40-IT
- Lead Sponsor
- FONDAZIONE FADOI
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1168
1) 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.
2) Any type of cancer (other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumor or known intracerebral metastases and acute leukemia) that meets at least one of the following:
• Active cancer defined as diagnosis of cancer within six months before the study inclusion, or receiving treatment for cancer at the time of inclusion or any treatment for cancer during 6 months prior to randomization, or recurrent locally advanced or metastatic cancer.
• Cancer diagnosed within 2 years before the study inclusion (history of cancer).
3) Signed and dated informed consent, available before the start of any specific trial procedure.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 818
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 350
1) Age <18 years
2) ECOG Performance Status III or IV;
3) Life expectancy of less than 6 months;
Related to anticoagulant treatment:
4) Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization;
5) 3 or more doses of a vitamin K antagonist before randomization;
6) Thrombectomy, vena cava filter insertion, or thrombolysis used to manage the index episode;
7) Iindication for anticoagulant treatment for a disease other than the index VTE episode;
8) Concomitant use of strong inhibitors or inducers of both cytochrome P-450 3A4 and P-Glycoprotein (see Appendix 1);
Related to bleeding risk:
9) Concomitant thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin over 165 mg daily or dual antiplatelet therapy;
10) Active bleeding or high risk of bleeding contraindicating anticoagulant treatment
11) Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery
12) Hemoglobin level lower than 8 g/dL (5.0 mmol/L) or platelet count <75x109/L or history of heparin-induced thrombocytopenia;
13) Creatinine clearance < 30 ml /min based on the Cockcroft Gault equation;
14) 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;
15) Uncontrolled hypertension (systolic BP> 180 mm Hg or diastolic BP > 100 mm Hg despite antihypertensive treatment);
Standard criteria:
16) Bacterial endocarditis;
17) Hypersensitivity to the study drugs or to any of their excipients;
18) Patients participation in other pharmaco therapeutic program with an experimental therapy that is known to effect the coagulation system.
19) Women of childbearing potential (WOCBP) who do not practice a medically accepted highly effective contraception during the trial and one month beyond. Highly effective contraception methods are:
a. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
b. progestogen-only hormonal contraception associated with inhibition of ovulation
c. intrauterine device (IUD)
d. intrauterine hormone-releasing system (IUS)
e. bilateral tubal occlusion
f. vasectomized partner
g. sexual abstinence ;
20) Pregnancy, or breast feeding
21) Any condition that, as judged by the investigator, would place the subject at increased risk of harm if he/she participated in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The aim of this study is to assess whether apixaban is non-inferior to the LMWH dalteparin for the treatment of newly diagnosed proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in patients with cancer.;Secondary Objective: Not applicable;Primary end point(s): Primary efficacy outcome: objectively confirmed recurrent VTE occurring during the study period, that means the composite of:<br>• Proximal DVT of the lower limbs (symptomatic or unsuspected) <br>• DVT of the upper limb (symptomatic) <br>• PE (symptomatic or unsuspected<br><br>Primary safety outcome is major bleeding, defined (as per ISTH guidelines), as acute clinically overt bleeding.;Timepoint(s) of evaluation of this end point: 7 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary efficacy outcomes: <br>¿ The individual components of the primary efficacy outcome;<br>¿ Symptomatic recurrence of VTE;<br>¿ All cause death;<br>¿ The composite of primary efficacy outcome plus major bleeding;<br>¿ The composite of primary efficacy outcome plus major bleeding plus all cause death;<br>¿ The composite of primary efficacy outcome plus all cause death;<br>¿ Any major cardiovascular event, fatal or non-fatal (including acute myocardial infarction or ischemic stroke);<br>¿ All venous thromboembolic events (including splanchnic vein thrombosis and cerebral vein thrombosis);<br>¿ Quality of life (QoL) according to Anti-Clot Treatment Scale (ACTS) (see Appendix 2)<br>;Timepoint(s) of evaluation of this end point: 7 months