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Apixaban for the Prevention of Venous Thromboembolism in Cancer Patients (AVERT)

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ClinicalTrials.gov Identifier: NCT02048865
Recruitment Status : Completed
First Posted : January 29, 2014
Last Update Posted : November 20, 2018
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Bristol-Myers Squibb
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE January 27, 2014
First Posted Date  ICMJE January 29, 2014
Last Update Posted Date November 20, 2018
Actual Study Start Date  ICMJE March 24, 2014
Actual Primary Completion Date October 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
first episode of objectively documented, symptomatic or asymptomatic VTE (DVT and/or PE) [ Time Frame: 7 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2014)
first episode of objectively documented, symptomatic or asymptomatic VTE (DVT and/or PE) [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT02048865 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
Rate of adverse events [ Time Frame: 7 months ]
rate of clinical overt bleeding( major and minor bleeding) and death within the study period
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2014)
Rate of adverse events [ Time Frame: 12 months ]
rate of clinical overt bleeding( major and minor bleeding) and death within the study period
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Apixaban for the Prevention of Venous Thromboembolism in Cancer Patients
Official Title  ICMJE 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 7 Canadian centers (Ottawa, Halifax, Montreal, Vancouver, Sault Ste. Marie, Toronto 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 superiority 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  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Venous Thromboembolism
  • Cancer
Intervention  ICMJE
  • Drug: Apixaban
    Apixaban 2.5 mg tablets BID for 6 months
    Other Name: Eliquis
  • Drug: Placebo drug
    placebo drug 2.5mg BID for 6 months
Study Arms
  • Active Comparator: Apixaban
    2.5 mg BID for 6 months
    Intervention: Drug: Apixaban
  • Placebo Comparator: Placebo drug
    2.5 mg BID for 6 months
    Intervention: Drug: Placebo drug
Publications * Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. doi: 10.1056/NEJMoa1814468. Epub 2018 Dec 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2018)
575
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2014)
574
Actual Study Completion Date October 19, 2018
Actual Primary Completion Date October 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • A newly diagnosed cancer site or progression of the malignant disease after complete or partial remission.
  • Initiating a new course of chemotherapy with a minimum intent of 3 months therapy
  • A VTE risk stratification score of ≥ 2, according to the scoring method
  • Age 18 years old or older
  • Provide written informed consent

Exclusion Criteria:

  • Lesions or conditions at increased risk of clinically significant bleeding (eg. active peptic ulcer disease)
  • 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, 3 times the upper limit of normal). *
  • Diagnosis of basal cell or squamous cell carcinoma of the skin or 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 Cockroft and Gault formula.
  • Pregnancy***
  • Continuous anticoagulation with vitamin K antagonists, low-molecular-weight heparin (LMWH), or other oral anticoagulants
  • Weight < 40 Kg
  • Platelet count < 50 x 109/L
  • Known allergies to ingredients contained in apixaban
  • Use of any contraindicated medications with apixaban
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02048865
Other Study ID Numbers  ICMJE OHSN-20130563-01H
CV185-245 ( Other Grant/Funding Number: Bristol-Myers Squibb )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Ottawa Hospital Research Institute
Study Sponsor  ICMJE Ottawa Hospital Research Institute
Collaborators  ICMJE
  • Canadian Institutes of Health Research (CIHR)
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Phil Wells, MD Ottawa Hospital Research Institute
Principal Investigator: Marc Carrier, MD Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP