Synergistic Influence of Rivaroxaban on Inflammation and Coagulation Biomarkers in Patients With CAD and PAD on Aspirin Therapy

NCT04059679 | Unknown Phase 4 FDA Drug

• 1 other identifier: 1436289
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase IV, prospective biomarker study that will be conducted at Sinai Hospital of Baltimore. After screening for patients who were treated with aspirin, thirty patients will be treated with 81 mg enteric coated (EC) aspirin for 7 days in the "lead-in" period and then will be randomly treated with EC aspirin (81mg qd) or EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid) for 12 weeks. Platelet aggregation, soluble markers of platelet activation and inflammation, thrombin generation kinetics and tissue factor (TF)-induced platelet-fibrin clot strength will be assessed at baseline (after 7 days of treatment with 81 mg EC aspirin), and 4 and 12 weeks after randomization of the study drug administration.

Conditions

Coronary Artery Disease; Peripheral Artery Disease

Outcome Measures

Primary Outcomes (1)

• Relative Difference in maximal ADP-induced Platelet Aggregation

  Relative difference in maximal ADP-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks.

  12 weeks

Secondary Outcomes (9)

• Relative differences in TF-thrombin-induced platelet aggregation

  12 weeks

• Relative differences in alpha- thrombin-induced platelet aggregation

  12 weeks

• Relative differences in inflammation biomarkers

  12 weeks

• Relative differences in platelet-fibrin clot characteristics

  12 weeks

• Relative differences in shear-induced platelet aggregation

  12 weeks

Other Outcomes (1)

• First occurrence of modified ISTH major bleeding

  12 weeks

Study Arms (2)

EC aspirin (81mg qd)

ACTIVE COMPARATOR

Drug: Aspirin 81 mg

EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid)

EXPERIMENTAL

Drug: Rivaroxaban 2.5 Mg Oral Tablet; Drug: Aspirin 81 mg

Interventions

Rivaroxaban 2.5 Mg Oral Tablet DRUG

EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid)

EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid)

Aspirin 81 mg DRUG

EC aspirin 81 mg qd

EC aspirin (81mg qd); EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects meeting criteria for CAD$ must have one or more of the following:
• Myocardial infarction within the past 20 years, or
• Multivessel coronary disease\* with symptoms or with history of stable or unstable angina, or
• Multivessel percutaneous coronary intervention, or
• Multivessel CABG surgery (\* Refers to stenosis of ≥ 50% in 2 or more coronary arteries, confirmed using invasive coronary angiography, or noninvasive imaging or stress studies (eg, exercise or pharmacologic) suggestive of significant ischemia in 2 ≥ coronary territories; or in 1 coronary territory if at least 1 other territory has been revascularized.)
• $Subjects with the qualifying criteria of CAD must also met at least one of the following criteria:
• Age \> 65 years, or
• Age \<65 years and documented atherosclerosis or revascularization involving at least 2 vascular beds+, or at least 2 additional cardiovascular risk factors:
• Current smoker (within 1 year of randomization)
• Diabetes mellitus
• Renal dysfunction with estimated glomerular filtration rate of \<60 ml/min
• Heart failure
• Non-lacunar ischemic stroke \> 1 month ago
• Because CAD involves disease in the coronary vasculature, only one additional vascular bed is required: e.g. the aorta and arterial supply to the brain, gastro-intestinal tract, lower limbs, upper limbs, or kidneys.
• Subjects meeting criteria for PAD must have one or more of the following

You may not qualify if:

• High risk of bleeding
• Stroke within 1 month or any history of hemorrhagic or lacunar stroke
• Severe heart failure with known ejection fraction \<30% or New York Heart Association (NYHA) class III or IV symptoms
• Estimated glomerular filtration rate (eGFR)\<15 mL/min
• Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy
• Known non-cardiovascular disease that is associated with poor prognosis (e.g., metastatic cancer) or that increases the risk of an adverse reaction to study interventions.
• History of hypersensitivity or known contraindication for rivaroxaban, aspirin, or its excipients. Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (P-gp) (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus \[HIV\]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine.
• Participation in any investigational study within the last 60 days.
• Active liver disease or hepatic dysfunction, defined as AST or ALT \>3 x ULN as determined by laboratory test results drawn at or available during screening.
• Recipient of any major organ transplant (e.g., lung, liver, heart, bone marrow, renal).
• Subjects with prosthetic heart valves.
• Known major active infection or major hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction in the judgment of the investigator.
• Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 5 years.
• Subject is pregnant or breast feeding, or planning to become pregnant or to breastfeed during receipt of investigational products and within 15 weeks after the end of study treatment.
• Female subject who is unwilling to use at least 2 effective birth control methods for at least 1 month before screening and 15 weeks after the end of treatment with investigational products, unless the subject is sterilized or postmenopausal.

Sponsors & Collaborators

• LifeBridge Health: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

RECRUITING

Related Publications (1)

• Tantry U, Cummings C, Mackrell P, Gonze M, Ulloa K, Bafford R, Rout A, Sukhi A, Gurbel P. Synergistic influence of rivaroxaban on inflammation and coagulation biomarkers in patients with coronary artery disease and peripheral artery disease on aspirin therapy. Future Cardiol. 2020 Mar;16(2):69-75. doi: 10.2217/fca-2019-0091. Epub 2020 Mar 4.

  PMID: 32129681 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Peripheral Arterial Disease

Interventions

Rivaroxaban; Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Atherosclerosis; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Udaya Tantry, PhD

CONTACT

4106019467; ukstantry@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 16, 2019
• Study Start: January 30, 2020
• Primary Completion: March 1, 2021
• Study Completion: August 1, 2021
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)