Apixaban for the Prevention of Venous Thromboembolism in Cancer Patients | RxWiki

Apixaban for the Prevention of Venous Thromboembolism in Cancer Patients

Overview[ - collapse ][ - ]

Purpose	Cancer patients have an increased risk of developing blood clots in the veins compared to non-cancer patients. Cancer patients who develop blood clots can lead to reduced life expectancy, delayed cancer treatment, and decreased quality of life. Prevention is the most effective way to decrease the complications associated with blood clots in the veins. Although previous clinical trials have shown some benefit on the use of medication to prevent blood clots in the veins in ambulatory cancer patients, these studies have been inconclusive in demonstrating that existing blood thinners significantly reduce the rate of blood clots in cancer patients. One possible explanation relates to the fact that these studies have included a large proportion of cancer patients who are a low risk of developing blood clots in the veins. We are proposing to identify cancer patients who are at a high risk of developing blood clots by using a validated tool at the time of their cancer diagnosis. The identified high risk cancer patients will be asked to participate in a trial to test the safety and efficacy of a new oral medication that has been used to prevent blood clots in patients undergoing surgery. We are enrolling 574 patients in 5 Canadian centers (Ottawa, Halifax, Montreal, Vancouver, and Hamilton). 287 patients will receive the study drug and 287 will receive an inactive substance. Analysis will be performed to assess the safety and the superiorty of the study drug.
Condition	Venous Thromboembolism Cancer
Intervention	Drug: Apixaban Drug: Placebo drug
Phase	Phase 2
Sponsor	Ottawa Hospital Research Institute
Responsible Party	Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier	NCT02048865
First Received	January 27, 2014
Last Updated	February 7, 2014
Last verified	February 2014

Tracking Information[ + expand ][ + ]

First Received Date	January 27, 2014
Last Updated Date	February 7, 2014
Start Date	January 2014
Estimated Primary Completion Date	June 2017
Current Primary Outcome Measures	first episode of objectively documented, symptomatic or asymptomatic VTE (DVT and/or PE) [Time Frame: 6 months] [Designated as safety issue: No]
Current Secondary Outcome Measures	Rate of adverse events [Time Frame: 12 months] [Designated as safety issue: Yes]rate of clinical overt bleeding( major and minor bleeding) and death within the study period

Descriptive Information[ + expand ][ + ]

Brief Title	Apixaban for the Prevention of Venous Thromboembolism in Cancer Patients
Official Title	Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients: A Randomized Placebo-Controlled, Double-Blind Clinical Trial
Brief Summary	Cancer patients have an increased risk of developing blood clots in the veins compared to non-cancer patients. Cancer patients who develop blood clots can lead to reduced life expectancy, delayed cancer treatment, and decreased quality of life. Prevention is the most effective way to decrease the complications associated with blood clots in the veins. Although previous clinical trials have shown some benefit on the use of medication to prevent blood clots in the veins in ambulatory cancer patients, these studies have been inconclusive in demonstrating that existing blood thinners significantly reduce the rate of blood clots in cancer patients. One possible explanation relates to the fact that these studies have included a large proportion of cancer patients who are a low risk of developing blood clots in the veins. We are proposing to identify cancer patients who are at a high risk of developing blood clots by using a validated tool at the time of their cancer diagnosis. The identified high risk cancer patients will be asked to participate in a trial to test the safety and efficacy of a new oral medication that has been used to prevent blood clots in patients undergoing surgery. We are enrolling 574 patients in 5 Canadian centers (Ottawa, Halifax, Montreal, Vancouver, and Hamilton). 287 patients will receive the study drug and 287 will receive an inactive substance. Analysis will be performed to assess the safety and the superiorty of the study drug.
Detailed Description	Patients holding a malignancy have a 7 to 28-fold higher risk for venous thromboembolism (VTE) than non-cancer patients(1). Since most cancer patients are currently treated in the outpatient setting, an acute episode of VTE has important implications on their care due to its effects on reduced life expectancy, high rates of VTE recurrence, therapeutic failures, delays in chemotherapy and the risk of bleeding during anticoagulation. The best treatment of an acute episode of VTE is its prevention (thromboprophylaxis). Although previous clinical trials have shown some benefit on the use of thromboprophylaxis in ambulatory cancer patients, these studies have been inconclusive to convincingly demonstrate that existing anticoagulants significantly reduce the rate of VTE in cancer patients. Possible explanations are related to the fact that these studies have included a large number of cancer patients whose risk for VTE has been low and in consequence, the benefit of anticoagulation has become diluted by the large proportion of low risk cancer patients. To increase the success of thromboprophylaxis in cancer outpatients, we propose, first, to include validated methods for predicting the risk of VTE at the time of cancer diagnosis(2, 3). This strategy will facilitate to identify cancer patients at high-risk for VTE and then, optimize the risk-to benefit ratio with anticoagulation. Second, to assess safety and efficacy of new oral anticoagulants in cancer patients as they represent an attractive alternative for an extended use of thromboprophylaxis. As a choice, new oral agents can be administered in fixed doses, do not require laboratory monitoring, have minimal interaction with additional drugs and provide a pain free alternative in patients who require injections. Reference List 1. Blood Coagul Fibrinolysis 2011. Blood Coagul Fibrinolysis 2011;22:86-91. 2. Blood 2010. Blood 2010;116:5377-5382. 3. Blood 2008. Blood 2008;111:4902-4907.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Condition	Venous Thromboembolism Cancer
Intervention	Drug: Apixaban Apixaban 2.5 mg tablets BID for 6 months Other Names: EliquisDrug: Placebo drug placebo drug 2.5mg BID for 6 months
Study Arm (s)	Active Comparator: Apixaban 2.5 mg BID for 6 months Placebo Comparator: Placebo drug 2.5 mg BID for 6 months

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	574
Estimated Completion Date	June 2017
Estimated Primary Completion Date	January 2017
Eligibility Criteria	Inclusion Criteria: - Patient with a newly diagnosed cancer site (except basal cell and squamous cell carcinoma of the skin) or progression of the malignant disease after complete or partial remission who have not recently received chemotherapy (≤ 3 months), radiotherapy and surgery (≤ 2 weeks). - Patient with a VTE risk stratification score of ≥ 2, according to the our scoring method - Age 18 years old or older - Provide written informed consent Exclusion Criteria: - Objectively confirmed substantial liver insufficiency as defined by clinical manifestations of ascites, cirrhosis, encephalopathy and/or jaundice and/or biochemical abnormalities in liver function tests including hypoalbuminemia (< 3.5 gr/dL), elevated levels of total bilirubin (> 25 umol/L), elevated liver transaminases (2 times the upper limit of normal) and/or biochemical diagnosis of biliary tract obstruction (elevated levels of gamma-glutamyl transferase and alkaline phosphatase). - Diagnosis of acute leukemia or myelodysplastic syndrome - Planned stem cell transplant - Life expectancy less than 6 months - Acute or chronic renal insufficiency with glomerular filtration rate (GFR) < 30 ml/min calculated by the modified Cockrot and Gault formula.4 - Pregnancy - Confirmed venous or arterial thromboembolism within the last 3 months. - Continuous anticoagulation with vitamin K antagonists, low-molecular weight heparin (LMWH), or other oral anticoagulants - Weight less than 40 Kg - Platelet counts < 50 x 109/L - Known allergies to ingredients contained in apixaban
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Marc Carrier, MD 613-737-8899 mcarrier@toh.on.ca
Location Countries	Canada

Administrative Information[ + expand ][ + ]

NCT Number	NCT02048865
Other Study ID Numbers	OHSN-20130563-01H
Has Data Monitoring Committee	Yes
Information Provided By	Ottawa Hospital Research Institute
Study Sponsor	Ottawa Hospital Research Institute
Collaborators	Canadian Institutes of Health Research (CIHR) Bristol-Myers Squibb
Investigators	Principal Investigator: Phil Wells, MD Ottawa Hospital Research InstitutePrincipal Investigator: Marc Carrier, MD Ottawa Hospital Research Institute
Verification Date	February 2014

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