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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

Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE May 24, 2019
Last Update Posted Date September 13, 2019
Estimated Study Start Date  ICMJE October 2019
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
Brachial vasoreactivity [ Time Frame: Baseline to 4 weeks ]
Change in Percent flow-mediated vasodilation (FMD)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03962855 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Peripheral Arterial Tonometry [ Time Frame: Baseline to 4 weeks ]
    Change in log transformed Reactive Hyperemia Index (LnRHI)
  • Non-platelet thromboxane generation [ Time Frame: Baseline to 4 weeks ]
    Change in urine 11-dehydrothromboxane B2
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 21, 2019)
  • Oxidative stress [ Time Frame: Baseline to 4 weeks ]
    Change in urine 8-isoPGF2a
  • Renal Prostanoid Excretion [ Time Frame: Baseline to 4 weeks ]
    Change in urine TXB2, 6-ketoPGF1α and the ratio of TXB2 to 6-ketoPGF1α,
  • 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
  • Inflammatory Markers [ Time Frame: Baseline to 4 weeks ]
    Change in hs-CRP and ICAM-1
  • Coagulation Markers [ Time Frame: Baseline to 4 weeks ]
    Change in soluble tissue factor and activated protein C
  • Renal Function [ Time Frame: Baseline to 4 weeks ]
    Change in eGFR
  • Cardiac Function [ Time Frame: Baseline to 4 weeks ]
    Change in NT pro-BNP
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Thromboxane Receptor Antagonist to Improve Endothelial Cell Function
Official Title  ICMJE The Thromboxane Receptor Antagonist to Blunt the Effects of Non-Platelet Thromboxane Generation and Improve Endothelial Cell Function (TRAP) Trial
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Cardiovascular Diseases
  • Vascular Dilation
Intervention  ICMJE
  • Drug: Ifetroban Sodium
    Ifetroban sodium 250 mg capsule once daily for 4 weeks
  • Other: Placebo
    Placebo arm to match Ifetroban Sodium once daily for 4 weeks.
Study Arms  ICMJE
  • Active Comparator: Ifetroban
    Ifetroban 250 mg oral capsule administered once daily for a minimum of 4 weeks.
    Intervention: Drug: Ifetroban Sodium
  • Placebo Comparator: Placebo
    Matching placebo administered once daily for a minimum of 4 weeks.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 21, 2019)
52
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Noelle Bodkin, BS, MS 508-856-1014 Noelle.Bodkin@umassmed.edu
Contact: Susan Papalia, BSN 508-856-1014 Susan.Papalia@umassmed.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03962855
Other Study ID Numbers  ICMJE UMMS-TPRA-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jeffrey Rade, University of Massachusetts, Worcester
Study Sponsor  ICMJE Jeffrey Rade
Collaborators  ICMJE
  • American Heart Association
  • Cumberland Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Jeffrey J Rade, MD University of Massachusetts, Worcester
PRS Account University of Massachusetts, Worcester
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP