Rivaroxaban Versus Warfarin in the Evaluation of Progression of Coronary Calcium

• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02376010
• Collaborator: (none)
• Enrollment: 110
• Location: 1
• Arms: 2
• Actual Duration (Months): 36
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

Current oral anti-coagulation for atrial fibrillation is most commonly performed with warfarin. Warfarin is a vitamin K antagonist that has been shown in non-randomized trials to increase vascular calcification. Increased vascular calcification has been tied to increased cardiovascular events (CVE). This study will randomize patients currently taking warfarin to either continue on warfarin or be switched to rivaroxaban. Rivaroxaban is an oral anti-coagulant that works by inhibiting Factor Xa, and has no interaction with vitamin K. This study is a randomized, open label study that will randomize 120 patients and have them undergo blood tests and a calcium scan at baseline, and again after 12 months. Patients will be seen quarterly for examinations, safety checks and supply of rivaroxaban, as well as follow up INR testing for warfarin.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: rivaroxaban; Drug: Warfarin	Phase 4

Detailed Description

Rivaroxaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with warfarin. The rate of myocardial infarction was 9% lower in the rivaroxaban group than in the warfarin group in the Rocket AF study and similarly the myocardial infarction rate was 12% lower in the apixaban group in Aristotle, but the difference was not significant in either trial. The potential of long term benefit by avoiding VKA therapy may be much greater for a CV event reduction. The study proposed will evaluate markers of CAC progression and atherosclerosis development, which have long term outcome data supporting that slowing these processes will be associated with lower CV events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized controlled trial, with blinded randomization to one of two groups.randomized controlled trial, with blinded randomization to one of two groups.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Rivaroxaban Versus Warfarin in the Evaluation of Progression of Coronary Calcium
• Actual Study Start Date: Apr 2, 2015
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: rivaroxaban rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR)	Drug: rivaroxaban
Active Comparator: warfarin warfarin orally once a day, titrated to INR of 2-3	Drug: Warfarin

Outcome Measures

Primary Outcome Measures

1. Coronary Artery Calcium (Serial Calcium Scans) [1 year]

   serial calcium scans

Secondary Outcome Measures

1. Atherosclerotic Plaque (Measures of Total Atherosclerosis Plaque on Serial CCTA) [1 year]

   measures of total atherosclerosis plaque on serial CCTA

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 84 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Eligible patients with atrial fibrillation at enrollment or two or more episodes of atrial fibrillation or flutter, as documented by electrocardiography, at least 2 weeks apart in the 12 months before enrollment

2. Age 18-84

3. On Warfarin for 6 months prior to enrollment at a stable dose.

4. Willingness to participate in the study and ability to sign informed consent

5. Minimum CAC score of 10

Key Exclusion Criteria:

1. Atrial fibrillation due to a reversible cause, moderate or severe mitral stenosis, or conditions other than atrial fibrillation that require anticoagulation (e.g., a prosthetic heart valve)

2. Prior apixaban, dabigatran, rivaroxaban use.

3. A need for aspirin at a dose of >165 mg a day or for both aspirin and clopidogrel,

4. Renal insufficiency (serum creatinine level of 12.5 mg per deciliter or calculated creatinine clearance of <50 ml per minute).

5. Serious bleeding event in the previous 6 months or a high risk of bleeding (eg, active peptic ulcer disease, a platelet count of <100,000/mm3 or hemoglobin level of <10 g/dL, stroke within the previous 10 days, documented hemorrhagic tendencies, or blood dyscrasias)

6. Weight in excess of 325 pounds

7. Resting hypotension (systolic blood pressure of <90mmHg) or resting hypertension (systolic blood pressure of >170mmHg or diastolic blood pressure of >110 mmHg).

8. History of active malignancy requiring concurrent chemotherapy.

9. Any unstable medical, psychiatric, or substance abuse disorder that in the opinion of the principal investigator is likely to affect the subject's ability to complete the study.

10. Known allergy to iodinated contrast material

11. Pregnancy or breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles Biomedical Research Institute	Torrance	California	United States	90502

Sponsors and Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 2, 2015

More Information

Publications

None provided.

• Responsible Party: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT02376010
• Other Study ID Numbers: 21429
• First Posted: Mar 3, 2015
• Last Update Posted: Jul 22, 2021
• Last Verified: Mar 1, 2017

• Keywords provided by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: atherosclerosis; coronary artery disease; cardiac CT; computed tomographic angiography
• Additional relevant MeSH terms: Atherosclerosis; Warfarin; Rivaroxaban

Study Results

Participant Flow

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR) rivaroxaban	warfarin orally once a day, titrated to INR of 2-3 Warfarin
Period Title: Overall Study
STARTED	55	55
COMPLETED	46	51
NOT COMPLETED	9	4

Baseline Characteristics

Arm/Group Title	Rivaroxaban	Warfarin	Total
Arm/Group Description	rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR) rivaroxaban	warfarin orally once a day, titrated to INR of 2-3 Warfarin	Total of all reporting groups
Overall Participants	55	55	110
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	42 76.4%	41 74.5%	83 75.5%
>=65 years	13 23.6%	14 25.5%	27 24.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62 (10)	60 (11)	61 (10)
Sex: Female, Male (Count of Participants)
Female	16 29.1%	17 30.9%	33 30%
Male	39 70.9%	38 69.1%	77 70%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.8%	2 3.6%	3 2.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 20%	11 20%	22 20%
White	43 78.2%	42 76.4%	85 77.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	55 100%	55 100%	110 100%

Outcome Measures

1. Primary Outcome

Title	Coronary Artery Calcium (Serial Calcium Scans)
Description	serial calcium scans
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

patients completed second scan with interpretable data

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR) rivaroxaban	warfarin orally once a day, titrated to INR of 2-3 Warfarin
Measure Participants	46	51
Median (Inter-Quartile Range) [mm cubed]	26.3	40.5

2. Secondary Outcome

Title	Atherosclerotic Plaque (Measures of Total Atherosclerosis Plaque on Serial CCTA)
Description	measures of total atherosclerosis plaque on serial CCTA
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

volume of plaque in patients completing study

Arm/Group Title	Rivaroxaban	Warfarin
Arm/Group Description	rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR) rivaroxaban	warfarin orally once a day, titrated to INR of 2-3 Warfarin
Measure Participants	46	51
Median (Inter-Quartile Range) [mm cubed]	20.1	30.1

Adverse Events

Time Frame	1 year
Arm/Group Title	Rivaroxaban		Warfarin
Arm/Group Description	rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR) rivaroxaban		warfarin orally once a day, titrated to INR of 2-3 Warfarin
All Cause Mortality
	Rivaroxaban		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/51 (0%)
Serious Adverse Events
	Rivaroxaban		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Rivaroxaban		Warfarin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/46 (2.2%)		2/51 (3.9%)
Blood and lymphatic system disorders
minor bleeding	1/46 (2.2%)	1	2/51 (3.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.