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Thromboxane Receptor Antagonist to Improve Endothelial Cell Function (TRAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03962855
Recruitment Status : Recruiting
First Posted : May 24, 2019
Last Update Posted : June 19, 2020
American Heart Association
Cumberland Pharmaceuticals
Information provided by (Responsible Party):
Jeffrey Rade, University of Massachusetts, Worcester

Brief Summary:
This study evaluates whether addition of the thromboxane receptor antagonist to chronic aspirin therapy improves endothelial function and reduces non-platelet thromboxane generation in patients with established cardiovascular disease. Half of participants will receive ifetroban and the other half will receive matchcing placebo for the 4 week study period.

Condition or disease Intervention/treatment Phase
Cardiovascular Diseases Vascular Dilation Drug: Ifetroban Sodium Other: Placebo Phase 2

Detailed Description:
Thromboxane is a prostaglandin produced in healthy individuals mainly in platelets, where it mediates platelet activation and vasoconstriction via binding to cellular thromboxane-prostanoid (TP) receptors. The cardioprotective effect of aspirin is due to suppression of platelet thromboxane generation and reactivity. Unfortunately 25-50% of patients with cardiovascular disease taking ASA continue to generate thromboxane from non-platelet sources, which significantly increases their risk of atherothrombosis and death. Evidence suggests that oxidative stress is a potent stimulus for thromboxane generation in endothelial cells that involves autocrine/paracrine signaling through the TP receptor. This clinical trial addresses the central hypothesis that vascular endothelial cells under oxidative stress are a major source of non-platelet thromboxane generation in patients with cardiovascular disease and that antagonism of the TP receptor will suppress its formation and improve endothelial function.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single center, prospectively randomized, double-blinded, placebo-controlled clinical trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Thromboxane Receptor Antagonist to Blunt the Effects of Non-Platelet Thromboxane Generation and Improve Endothelial Cell Function (TRAP) Trial
Actual Study Start Date : September 20, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : January 2022

Arm Intervention/treatment
Active Comparator: Ifetroban
Ifetroban 250 mg oral capsule administered once daily for a minimum of 4 weeks.
Drug: Ifetroban Sodium
Ifetroban sodium 250 mg capsule once daily for 4 weeks

Placebo Comparator: Placebo
Matching placebo administered once daily for a minimum of 4 weeks.
Other: Placebo
Placebo arm to match Ifetroban Sodium once daily for 4 weeks.

Primary Outcome Measures :
  1. Peripheral Arterial Tonometry [ Time Frame: Baseline to 4 weeks ]
    Change in Reactive Hyperemia Index (RHI)

Secondary Outcome Measures :
  1. Brachial vasoractivity [ Time Frame: Baseline to 4 weeks ]
    Change in Percent flow-mediated vasodilation (FMD)

  2. Non-platelet thromboxane generation [ Time Frame: Baseline to 4 weeks ]
    Change in urine 11-dehydrothromboxane B2

Other Outcome Measures:
  1. Oxidative stress [ Time Frame: Baseline to 4 weeks ]
    Change in urine 8-isoPGF2a

  2. Renal Prostanoid Excretion [ Time Frame: Baseline to 4 weeks ]
    Change in urine TXB2, 6-ketoPGF1α and the ratio of TXB2 to 6-ketoPGF1α,

  3. Prostacyclin Generation [ Time Frame: Baseline to 4 weeks ]
    Change in urine 2,3-dinor-6-ketoPGF1α and ratio of 11-dhTXB2 to 2,3-dinor-6-ketoPGF1α

  4. Inflammatory Markers [ Time Frame: Baseline to 4 weeks ]
    Change in hs-CRP and ICAM-1

  5. Coagulation Markers [ Time Frame: Baseline to 4 weeks ]
    Change in soluble tissue factor and activated protein C

  6. Renal Function [ Time Frame: Baseline to 4 weeks ]
    Change in eGFR

  7. Cardiac Function [ Time Frame: Baseline to 4 weeks ]
    Change in NT pro-BNP

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males and females ≥18 years of age with established cardiovascular disease
  • Take 81 mg daily of aspirin as part of their daily medical regimen
  • Urine thromboxane B2 metabolites >1500 pg/mg creatinine on screening.
  • Able to provide written consent and comply with protocol-specific procedures.

Exclusion Criteria:

  • Chronic oral anticoagulation.
  • ST segment myocardial infarction within 1 month.
  • Cardiac surgery within 1 month.
  • Ongoing uncontrolled severe inflammatory condition.
  • Pregnant or lactating.
  • Ifetroban or aspirin sensitivity
  • Inability to perform vascular testing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03962855

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Contact: Susan Papalia, BSN 508-856-1014

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United States, Massachusetts
University of Massachusetts Medical School Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Jeffrey J Rade, MD    774-441-6310   
Contact: Susan Papalia, RN    508-856-1014   
Principal Investigator: Jeffreyt J Rade, MD         
Sponsors and Collaborators
Jeffrey Rade
American Heart Association
Cumberland Pharmaceuticals
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Principal Investigator: Jeffrey J Rade, MD University of Massachusetts, Worcester
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Responsible Party: Jeffrey Rade, Professor, University of Massachusetts, Worcester Identifier: NCT03962855    
Other Study ID Numbers: UMMS-TPRA-01
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: June 19, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cardiovascular Diseases
Platelet Aggregation Inhibitors