The Influence of Febuxostat on Coronary Artery Endothelial Dysfunction in Participants With Chronic Stable Angina

NCT01763996 | Completed Phase 4 Results

• 2 other identifiers: CCR-FEB-002U1111-1136-2270
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effect of febuxostat on coronary artery flow in patients with coronary artery disease.

Conditions

Coronary Artery Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change in Coronary Artery Flow From Rest to Isometric Handgrip (IHG) Exercise at the End of the Administration of Febuxostat and Placebo

  Coronary artery flow was measured using magnetic resonance imaging (MRI) at rest and during sustained isometric (static) handgrip exercises. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.

  Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)

Secondary Outcomes (10)

• Change in Coronary Artery Cross-Sectional Area From Rest to IHG Exercise at the End of the Administration of Febuxostat and Placebo

  Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)

• Change in Coronary Flow Velocity From Rest to IHG Exercise at the End of the Administration of Febuxostat and Placebo

  Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)

• Change in Coronary Artery Flow Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo

  Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)

• Change in Coronary Artery Cross Sectional Area Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo

  Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)

• Change in Coronary Flow Velocity Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo

  Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)

Study Arms (2)

Sequence 1: Febuxostat 80 mg + Placebo

EXPERIMENTAL

Febuxostat 80 mg, capsules, orally, once daily for 6 weeks in Period 1, followed by febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 2.

Drug: Febuxostat; Drug: Febuxostat placebo

Sequence 2: Placebo + Febuxostat 80 mg

EXPERIMENTAL

Febuxostat placebo-matching capsules, orally, once daily for 6 weeks in Period 1, followed by febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 2.

Drug: Febuxostat; Drug: Febuxostat placebo

Interventions

Febuxostat DRUG

Febuxostat capsules

Sequence 1: Febuxostat 80 mg + Placebo; Sequence 2: Placebo + Febuxostat 80 mg

Febuxostat placebo DRUG

Febuxostat placebo-matching capsules

Sequence 1: Febuxostat 80 mg + Placebo; Sequence 2: Placebo + Febuxostat 80 mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Has a serum urate ≥4.0 mg/dL.
• Has a history of coronary artery disease, defined as:
• ≥50 % stenosis of ≥1 major coronary artery confirmed by angiography; OR
• Documented prior myocardial infarction (MI) by enzymes/electrocardiogram (ECG) changes; OR
• Documented prior exercise or pharmacologic stress/echo myocardial imaging study positive for ischemia.
• Has estimated glomerular filtration rate (eGFR) ≥30 mL/min by Modification of Diet in Renal Disease (MDRD) at the screening visit.
• Has a change in coronary artery flow from rest to isometric handgrip exercise of less than + 10 mL/min.
• Is male or female and aged 18 to 85 years, inclusive.
• A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
• Is on stable (30 days prior to Screening Day-21) medication doses prescribed for any underlying medical condition (ie, hypertension, angina) and is expected to remain on stable doses throughout the study duration.
• Is able to take nitroglycerin for anginal symptoms during study procedures.

You may not qualify if:

• Has received any investigational compound within 30 days prior to Screening.
• Has received allopurinol or febuxostat in a previous clinical study or as a therapeutic agent with-in 6 months of randomization.
• Has gout or secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ transplant) or has experienced a gout flare.
• Has a history of xanthinuria.
• Has known contraindication to magnetic resonance imaging (MRI) scanning
• Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has a history of hypersensitivity or allergies to febuxostat or nitroglycerin.
• Has hemoglobin \<10 g/L at Screening.
• Has a history or clinical manifestations of a significant medical condition that might affect his/her ability to complete the study.
• Has any of the following during Screening:
• New York Heart Association Class III or IV heart failure.
• Acute coronary syndrome or a coronary revascularization procedure within 2 months of Screening.
• Wolff-Parkinson-White syndrome.
• Pacemaker or implantable cardioverter defibrillator.
• Arrhythmias (ie, supraventricular tachycardia (SVT), atrial fibrillation/flutter, or ventricular tachycardia (VT) during Screening).

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Baltimore, Maryland, United States

Location

Related Publications (1)

• Hays AG, Iantorno M, Schar M, Lai S, Czarny M, Breton E, Palmer RN, Whelton A, Weiss RG, Gerstenblith G. The influence of febuxostat on coronary artery endothelial dysfunction in patients with coronary artery disease: A phase 4 randomized, placebo-controlled, double-blind, crossover trial. Am Heart J. 2018 Mar;197:85-93. doi: 10.1016/j.ahj.2017.11.006. Epub 2017 Nov 23.

  PMID: 29447788 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Febuxostat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 9, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 13, 2016
• Results First Posted: April 13, 2016

Record last verified: 2016-03

Locations

US (1)