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

Primary Purpose

Coronary Artery Disease, Peripheral Artery Disease

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Rivaroxaban 2.5 Mg Oral Tablet
Aspirin 81 mg
Sponsored by
LifeBridge Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Coronary Artery Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: to qualify, all subjects must meet have CAD and PAD as according to criteria specified below:

  • 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:

    1. Current smoker (within 1 year of randomization)
    2. Diabetes mellitus
    3. Renal dysfunction with estimated glomerular filtration rate of <60 ml/min
    4. Heart failure
    5. 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
  • Previous aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac, or infrainguinal arteries, or
  • Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma), or
  • History of intermittent claudication and one of the following

    • An ankle/arm blood pressure (BP) ratio < 0.90,
    • Significant peripheral artery or venous stenosis of ≥50% documented by angiography or by duplex ultrasound
    • Previous carotid revascularization or asymptomatic carotid artery stenosis ≥ 50% as diagnosed using duplex ultrasound or angiography.

      • Subject may be of either sex and of any race, and must be >18 years of age.
      • Subject agrees to not participate in any other investigational or invasive clinical study for a period of 4 months during the study period
      • The subject is able to read and has signed and dated the informed consent document including authorization permitting release of personal health information approved by the investigator's Institutional Review Board (IRB).

Exclusion Criteria: Subjects will be excluded from entry if ANY of the criteria listed below are met:

  • 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.
  • Subject likely to not be available to complete all protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge.
  • History or evidence of any other clinically significant disorder, condition, or disease other than those outlined above that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

Sites / Locations

  • Sinai Hospital of BaltimoreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

EC aspirin (81mg qd)

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

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Relative differences in TF-thrombin-induced platelet aggregation
Relative differences in TF-thrombin-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks.
Relative differences in alpha- thrombin-induced platelet aggregation
Relative differences in alpha- thrombin-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks.
Relative differences in inflammation biomarkers
Relative differences in IL-6, hsCRP, platelet bound p-selectin, VCAM, fibrinogen, oxLDL, oxLDL/atherox, TAT complexes, prothrombin F1+2, D-dimer and FpA (soluble markers) between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Relative differences in platelet-fibrin clot characteristics
Relative differences in platelet-fibrin clot characteristics between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Relative differences in shear-induced platelet aggregation
Relative differences in shear-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Relative differences in lag time
Relative differences in lag time between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Relative differences in peak thrombin production
Relative differences in peak thrombin production between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Relative differences in mean velocity rate index
Relative differences in mean velocity rate index between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Relative differences in endogenous thrombin potential
Relative differences in endogenous thrombin potential between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks

Full Information

First Posted
August 14, 2019
Last Updated
October 12, 2020
Sponsor
LifeBridge Health
Collaborators
Janssen Scientific Affairs, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04059679
Brief Title
Synergistic Influence of Rivaroxaban on Inflammation and Coagulation Biomarkers in Patients With CAD and PAD on Aspirin Therapy
Official Title
Synergistic Influence of Rivaroxaban on Inflammation and Coagulation Biomarkers in Patients With CAD and PAD on Aspirin Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 30, 2020 (Actual)
Primary Completion Date
March 2021 (Anticipated)
Study Completion Date
August 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LifeBridge Health
Collaborators
Janssen Scientific Affairs, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Peripheral Artery Disease

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EC aspirin (81mg qd)
Arm Type
Active Comparator
Arm Title
EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban 2.5 Mg Oral Tablet
Intervention Description
EC aspirin (81mg qd) plus rivaroxaban (2.5 mg bid)
Intervention Type
Drug
Intervention Name(s)
Aspirin 81 mg
Intervention Description
EC aspirin 81 mg qd
Primary Outcome Measure Information:
Title
Relative Difference in maximal ADP-induced Platelet Aggregation
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Relative differences in TF-thrombin-induced platelet aggregation
Description
Relative differences in TF-thrombin-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks.
Time Frame
12 weeks
Title
Relative differences in alpha- thrombin-induced platelet aggregation
Description
Relative differences in alpha- thrombin-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks.
Time Frame
12 weeks
Title
Relative differences in inflammation biomarkers
Description
Relative differences in IL-6, hsCRP, platelet bound p-selectin, VCAM, fibrinogen, oxLDL, oxLDL/atherox, TAT complexes, prothrombin F1+2, D-dimer and FpA (soluble markers) between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Title
Relative differences in platelet-fibrin clot characteristics
Description
Relative differences in platelet-fibrin clot characteristics between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Title
Relative differences in shear-induced platelet aggregation
Description
Relative differences in shear-induced platelet aggregation between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Title
Relative differences in lag time
Description
Relative differences in lag time between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Title
Relative differences in peak thrombin production
Description
Relative differences in peak thrombin production between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Title
Relative differences in mean velocity rate index
Description
Relative differences in mean velocity rate index between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Title
Relative differences in endogenous thrombin potential
Description
Relative differences in endogenous thrombin potential between 81mg qd EC aspirin or 81mg qd EC aspirin plus 2.5 mg bid rivaroxaban therapy for 12 weeks
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
First occurrence of modified ISTH major bleeding
Time Frame
12 weeks

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: to qualify, all subjects must meet have CAD and PAD as according to criteria specified below: 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 Previous aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac, or infrainguinal arteries, or Previous limb or foot amputation for arterial vascular disease (i.e., excludes trauma), or History of intermittent claudication and one of the following An ankle/arm blood pressure (BP) ratio < 0.90, Significant peripheral artery or venous stenosis of ≥50% documented by angiography or by duplex ultrasound Previous carotid revascularization or asymptomatic carotid artery stenosis ≥ 50% as diagnosed using duplex ultrasound or angiography. Subject may be of either sex and of any race, and must be >18 years of age. Subject agrees to not participate in any other investigational or invasive clinical study for a period of 4 months during the study period The subject is able to read and has signed and dated the informed consent document including authorization permitting release of personal health information approved by the investigator's Institutional Review Board (IRB). Exclusion Criteria: Subjects will be excluded from entry if ANY of the criteria listed below are met: 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. Subject likely to not be available to complete all protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge. History or evidence of any other clinically significant disorder, condition, or disease other than those outlined above that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Udaya Tantry, PhD
Phone
4106019467
Email
ukstantry@gmail.com
Facility Information:
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Udaya Tantry, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32129681
Citation
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.
Results Reference
derived

Learn more about this trial

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

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