Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism

Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism (COVET)

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03196349

Acronym

COVET

Enrollment

Registered

2017-06-22

Start date

2018-08-01

Completion date

2019-05-01

Last updated

2019-12-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Venous Thromboembolism

Brief summary

Comparison of Oral anticoagulants (warfarin, apixaban and rivaroxaban) for extended VEnous Thromboembolism.

Detailed description

Determine if apixaban is superior to warfarin in the reduction of clinically relevant bleeding. Determine if rivaroxaban is superior to warfarin in the reduction of clinically relevant bleeding. Determine if apixaban is non-inferior to warfarin in the prevention of recurrent venous thromboembolism. Determine if rivaroxaban is non-inferior to warfarin in the prevention of recurrent venous thromboembolism. An exploratory comparison of apixaban versus rivaroxaban for the prevention of clinically relevant bleeding and recurrent Venous Thromboembolism (VTEs) as a secondary objective.

Interventions

DRUGWarfarin

Will be randomized to receive open label warfarin daily to achieve a target INR of 2-3

DRUGApixaban 2.5 MG

Will be randomized to receive open label apixaban of 2.5 mg twice daily

DRUGRivaroxaban 10 MG

Will be randomized to receive open label rivaroxaban of 10mg daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

3.1 Inclusion Criteria To be eligible for this trial, patients must meet all of the following criteria: * Have confirmed acute, symptomatic, first lower extremity proximal DVT and/or PE that is NOT associated with a transient risk factor. * Have completed an initial treatment course of oral anticoagulant therapy for 3-12 months and have a recommendation from their provider to continue anticoagulation indefinitely. * Have the capacity to understand and sign an informed consent form. * Be 18 years of age and older. * Under the direct care of a healthcare provider for treatment of VTE for the length of time in the study. 3.2

Exclusion criteria

If a patient meets any of the following criteria, he or she may not be enrolled in the study: * Creatinine clearance (CrCl) \< 30 mL/min as determined by Cockcroft-Gault formula documented within 3 months from date of consent * Significant liver disease (Child-Pugh B or C) * Concomitant use of medications that are strong P-glycoprotein or CYP3A4 inducers/inhibitors * Another indication for chronic therapeutic-dose anticoagulation, such as atrial fibrillation (i.e., rivaroxaban, 10 mg daily, or apixaban, 2.5 mg twice daily, would not be appropriate therapy) * A clinical indication for a specific anticoagulant regimen (e.g., warfarin with a target INR of 2-3 is recommended for patients with 'triple-positive' antiphospholipid syndrome). * Life expectancy \< 3 months * Currently pregnant or breast feeding * Unable / unwilling to pay for one (or more) of the treatment options * Active Cancer defined as: Diagnosed with cancer within the past 6 months; or Recurrent, regionally advanced or metastatic disease; Currently receiving treatment or have received any treatment for cancer during the 6 months prior to randomization; or A hematologic malignancy not in complete remission • Unwilling / unlikely to agree to follow up

Design outcomes

Primary

Measure	Time frame	Description
Number of Subjects With Clinically Relevant Bleeding Events	Randomization to 12 months	Primary outcome of Clinically relevant bleeding (composite of major bleeding (MB) and/or clinically relevant non major bleeding (CRNMB))
Number of Subjects With Recurrent Venous Thromboembolism (VTE)	Randomization to 12 months	Primary efficacy outcome of recurrent VTE

Other

Measure	Time frame	Description
Number of Subjects With Premature Termination of Study Medication	Randomization to 12 months	Premature termination of study medication
Number of Subjects Experiencing Major Bleeding	Randomization to 12 months	Major bleeding
Number of Subjects Experiencing Vascular Events (Myocardial Infarction, Ischemic Stroke)	Randomization to 12 months	MI, ischemic stroke, peripheral arterial embolism
Number of Subjects Experiencing All-cause Mortality	Randomization to 12 months	All cause mortality
Number of Subjects Experiencing Clinically Relevant Non-major Bleeding	Randomization to 12 months	Clinically relevant non-major bleeding

Countries

United States

Participant flow

Participants by arm

Arm	Count
Warfarin Subjects randomized to Warfarin will have warfarin administered daily in order to maintain a target INR of 2-3 Warfarin: Will be randomized to receive open label warfarin daily to achieve a target INR of 2-3	16
Apixaban Subjects randomized to Apixaban will have apixaban administered study drug of 2.5mg twice daily Apixaban 2.5 MG: Will be randomized to receive open label apixaban of 2.5 mg twice daily	13
Rivaroxaban Subjects randomized to Rivaroxaban will have rivaroxaban administered study drug of 10 mg daily Rivaroxaban 10 MG: Will be randomized to receive open label rivaroxaban of 10mg daily	12
Total	41

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Did not receive study drug	0	1	2
Overall Study	No data entered	2	4	0
Overall Study	Study Terminated early	15	9	11

Baseline characteristics

Characteristic	Warfarin	Apixaban	Rivaroxaban	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	5 Participants	8 Participants	1 Participants	14 Participants
Age, Categorical Between 18 and 65 years	11 Participants	5 Participants	11 Participants	27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	2 Participants	1 Participants	2 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	14 Participants	10 Participants	8 Participants	32 Participants
Region of Enrollment Canada	6 participants	6 participants	3 participants	15 participants
Region of Enrollment United States	10 participants	7 participants	9 participants	26 participants
Sex: Female, Male Female	4 Participants	3 Participants	2 Participants	9 Participants
Sex: Female, Male Male	12 Participants	10 Participants	10 Participants	32 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 14	0 / 8	0 / 9
other Total, other adverse events	0 / 14	0 / 8	0 / 9
serious Total, serious adverse events	0 / 14	0 / 8	0 / 9

Outcome results

Primary

Number of Subjects With Clinically Relevant Bleeding Events

Primary outcome of Clinically relevant bleeding (composite of major bleeding (MB) and/or clinically relevant non major bleeding (CRNMB))