Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study

Phase 4

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: Rivaroxaban; Drug: Apixaban

• Registration Number: NCT02559856
• Lead Sponsor: Ottawa Hospital Research Institute

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.

Study Timeline

• Study First Submitted: 2015-09-21
• Study First Submitted QC: 2015-09-23
• Study First Posted: 2015-09-24
• Study Start: 2016-05
• Primary Completion: 2017-11
• Study Completion: 2018-02
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rivaroxaban	Rivaroxaban	15 mg PO twice-a-day for 3 weeks, then 20 mg PO once daily for 3 or 6 months of treatment.
Apixaban	Apixaban	10 mg PO twice-a-day for 1 week, then 5 mg PO, twice daily for 3 or 6 months of treatment.

Primary Outcome Measures

Name	Time	Method
Proportion of patients screened who are eligible to participate in the trial	For the duration of the study 3-6 months	Assessing clinical feasibility for a larger multi-center trial - number of screened patients versus eligible patients
Proportion of eligible patients who consent to participate in the trial	For the duration of the study 3-6 months	Assessing clinical feasibility for a larger multi-center trial - number of eligible patients versus patients who consent to participate
Proportion of patients who attend each follow-up visit	For the duration of the study 3-6 months	Assessing clinical feasibility for a larger multi-center trial - number of patients that miss visits versus patients that attend visits.
Proportion of patients completing all required study procedures, per follow-up visit	For the duration of the study 3-6 months	Assessing clinical feasibility for a larger multi-center trial - number of patients that complete all required procedures/study visits versus patients that do not.

Secondary Outcome Measures

Name	Time	Method
Bleeding Events	For the duration of the study 3-6 months	Major bleeding events, clinically relevant non-major and minor bleeding episodes
Venous Thromboembolism	For the duration of the study 3-6 months	Recurrent VTE and VTE related-death
Death	For the duration of the study 3-6 months	* All-cause mortality rates; * Individual rates of death related to VTE, cardiovascular disease, bleeding or other causes
Medication compliance	For the duration of the study 3-6 months	As assessed by study pill count
Time-to-event analysis	For the duration of the study 3-6 months	The time-to-first occurrence of secondary outcomes between randomization and end of follow-up

Trial Locations

Locations (4)

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

The Ottawa Hospital - General Campus; 🇨🇦 Ottawa, Ontario, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Hôtel-Dieu de Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada