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Thromboxane Receptor Antagonist to Improve Endothelial Cell Function (TRAP)

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ClinicalTrials.gov Identifier: NCT03962855
Recruitment Status : Not yet recruiting
First Posted : May 24, 2019
Last Update Posted : September 13, 2019
Sponsor:
Collaborators:
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
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : June 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. Brachial vasoreactivity [ Time Frame: Baseline to 4 weeks ]
    Change in Percent flow-mediated vasodilation (FMD)


Secondary Outcome Measures :
  1. Peripheral Arterial Tonometry [ Time Frame: Baseline to 4 weeks ]
    Change in log transformed Reactive Hyperemia Index (LnRHI)

  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



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

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 ClinicalTrials.gov identifier (NCT number): NCT03962855


Contacts
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Contact: Noelle Bodkin, BS, MS 508-856-1014 Noelle.Bodkin@umassmed.edu
Contact: Susan Papalia, BSN 508-856-1014 Susan.Papalia@umassmed.edu

Sponsors and Collaborators
Jeffrey Rade
American Heart Association
Cumberland Pharmaceuticals
Investigators
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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
ClinicalTrials.gov Identifier: NCT03962855     History of Changes
Other Study ID Numbers: UMMS-TPRA-01
First Posted: May 24, 2019    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: May 2019
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
Ifetroban
Platelet Aggregation Inhibitors