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Patients randomized in the apixaban reduced dose group will receive an apixaban 2.5 mg tablet and a placebo of apixaban 5 mg tablet, twice daily for 12 months.

Patients randomized in the apixaban full dose group will receive a placebo of apixaban 2.5 mg tablet and an apixaban 5 mg tablet, twice daily for 12 months.

Subjects will be randomized (1:1 ratio) to apixaban 5 mg bid (full dose) or apixaban 2.5 mg bid (reduced-dose) using a centralized IWRS (double blind study).

Apixaban 5 MG

Guy Meyer, Pr

The main objective is to determine whether a low-dose regimen of apixaban (2.5 mg bid) is non inferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent venous thromboembolism (VTE) in patients with active cancer who have completed at least 6 months of anticoagulant therapy for treating a documented index event of proximal deep venous thrombosis (DVT) (symptomatic or incidental) or pulmonary embolism (symptomatic or incidental).

For patients completing at least 6 months of anticoagulant therapy in whom the cancer is active, the thrombotic risk is arguably ongoing and indefinite anticoagulation seems required.

Given apixaban 5 mg bid is an alternative for the first 6 months of treatment, we intend to assess whether it is possible to lower the dose of apixaban (2.5 mg bid) after completing at least 6 months of anticoagulant treatment in a specific population of patients with cancer associated thrombosis (CAT) requiring extended anticoagulant treatment and with significant life expectancy. There are 2 conditions to be met : demonstrate the non-inferiority of the 2.5 mg bid regimen on the efficacy endpoint and then demonstrate the superiority of the 2.5 mg bid regimen as compared to the 5 mg bid on the safety endpoint.

It is a multicenter, international, prospective, randomized, parallel-group, double-blind non-inferiority trial with blinded adjudication of outcome events (approximately 160 centers in approximately 10 countries (France, Italy, Spain, Belgium, Greece, Netherlands, UK, Switzerland, Poland, Austria), with a number of expected inclusions of 11 patients per site.

Subjects should be randomized within 7 days after the last dose of their initial 6-month treatment, defined as the treatment ongoing after completing at least 6 months of anticoagulant treatment from the beginning of the anticoagulant treatment for the index event. This treatment may be low-molecular weight heparin (LMWH), direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA). If a VKA was used as standard anticoagulant therapy, then an INR must be documented as 2 or less before randomization. Every attempt should be made to randomize subjects as soon as possible after the initial treatment has been discontinued.

Subjects will be stratified based on the cancer site and the type of disease treated (PE with/without DVT or DVT alone). If a subject had both symptomatic DVT and symptomatic PE, the subject will be stratified as having symptomatic PE.

API-CAT STUDY for APIxaban Cancer Associated Thrombosis

Long-term Treatment of Cancer Associated VTE: Reduced vs Full Dose of Apixaban : API-CAT STUDY for APIxaban Cancer Associated Thrombosis

The incidence of an adjudicated composite of recurrent symptomatic VTE (proximal and/or distal DVT and/or symptomatic PE and/or upper limb or central venous catheter thrombosis or incidental VTE (proximal DVT or PE), or death due to PE during the treatment period.

Incidental VTE is defined as proximal DVT or PE detected by imaging incidentally when a patient undergoes imaging studies as standard of care for the management of the malignancy or other reasons but not for a VTE suspicion.

The definition of major bleeding described is adapted from the International Society on Thrombosis and Hemostasis (ISTH) definition (Schulman JTH 2005).

Recurrent VTE objectively confirmed after clinical suspicion

VTE related-death: PE based on objective diagnostic testing, autopsy, or sudden death; i.e. death occurring within one hour of the onset of new symptoms which cannot be attributed to a documented cause (unexplained death) and for which PE/DVT cannot be ruled out as the cause.

All deaths will be adjudicated by the ICAC and classified as either VTE-related, cancer death (including all deaths due to the underlying cancer), bleeding-related or others, including all deaths due to a clearly documented other cause, such as respiratory failure (e.g., terminal emphysema), infections/sepsis etc.

The definition of major bleeding described is adapted from the International Society on Thrombosis and Hemostasis (ISTH) definition (Schulman 2005) and includes

* Acute clinically overt bleeding with one or more of the following:

  * A decrease in hemoglobin (Hgb) of 2 g/dL or more
  * A transfusion of 2 or more units of packed red blood cells
  * Symptomatic bleeding that occurs in at least one of the following critical sites:

    * Intracranial
    * Intraspinal
    * Intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed)
    * Pericardial
    * Intra-articular
    * Intramuscular with compartment syndrome
    * Retroperitoneal
* Bleeding that is fatal: bleeding event that the independent adjudication committee determines is the primary cause of death or contributes directly to death.

Adjudicated composite of recurrent symptomatic VTE, VTE related-death, all-cause death, adjudicated major bleeding.

Spots Global Cancer Trial Database for apixaban 5 mg