Clinical trial NCT02559856: Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
Official title: Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism: The Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Venous Thromboembolism
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
First posted: 2015-09-24
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This vanguard pilot study compares rivaroxaban and apixaban, two of the new oral blood thinners for the treatment of blood clots. Half of the patients will receive apixaban and half will receive rivaroxaban. The main objective is to determine the feasibility of patient recruitment and resources required to follow enrolled patients and inform for a larger, multi-centered trial and to assess which one is safer.

Detailed description: Recently developed new oral anticoagulants (OAC) overcome some of the limitations of established therapy with vitamin K antagonists (VKA) and low molecular weight heparin (LMWH) for treatment of acute venous thromboembolism (VTE), due to ease of administration and more predictable pharmacokinetic properties. Many clinical questions about the new OAC remain unanswered because there have not been direct head-to-head comparison trials. For example, although studies have shown that rivaroxaban and apixaban are at least as effective and safe as LMWH and VKA, meta-analyses suggest that apixaban may be associated with lower bleeding risk. Concerns about the potential impact of medication non-adherence have been raised. Compliance with twice daily medications (e.g. apixaban) is often worse than once daily medications (e.g. rivaroxaban). Both of these medications are approved by Health Canada for treatment of VTE yet there is genuine uncertainty about which of the two direct OAC confer the best risk-to-benefit ratio.This is a multi-centre, prospective randomized open blinded end-point (PROBE) trial assessing clinical feasibility for a larger multi-centered trial comparing bleeding outcomes using apixaban vs. rivaroxaban for treatment of acute VTE. The primary objective of the study is to determine if it is feasible to conduct a large randomized multicenter trial comparing apixaban vs. rivaroxaban for the treatment of acute VTE. The secondary objectives are to assess safety and superiority of apixaban vs rivaroxaban.

Eligibility criteria: Inclusion Criteria:

* Confirmed newly diagnosed acute VTE (proximal lower extremity deep vein thrombosis and segmental or greater pulmonary embolism)
* Age ≥ 18 years old
* Written informed consent

Exclusion Criteria:

* Any contraindication for anticoagulation such as active bleeding
* Clinically significant liver disease or alanine aminotransferase (ALT) levels ≥ 3 times the upper limit of normal range
* Creatinine clearance \< 30 ml/min calculated with the Cockcroft-Gault formula (29)
* Known allergies to either apixaban or rivaroxaban
* Pregnancy
* Use of contraindicated medications with apixaban or rivaroxaban
* Active malignancy in the last 6 months (excluding localized skin malignancy)
* No private insurance coverage for the study drug or not willing to pay for study drug

Primary outcomes:
measure: Proportion of patients screened who are eligible to participate in the trial
timeFrame: For the duration of the study 3-6 months
measure: Proportion of eligible patients who consent to participate in the trial
timeFrame: For the duration of the study 3-6 months
measure: Proportion of patients who attend each follow-up visit
timeFrame: For the duration of the study 3-6 months
measure: Proportion of patients completing all required study procedures, per follow-up visit
timeFrame: For the duration of the study 3-6 months
Secondary outcomes:
measure: Bleeding Events
timeFrame: For the duration of the study 3-6 months
measure: Venous Thromboembolism
timeFrame: For the duration of the study 3-6 months
measure: Death
timeFrame: For the duration of the study 3-6 months
measure: Medication compliance
timeFrame: For the duration of the study 3-6 months
measure: Time-to-event analysis
timeFrame: For the duration of the study 3-6 months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Sherbrooke
country: Canada
facility: Hôtel-Dieu de Sherbrooke
state: Quebec
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Lana Castellucci, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: