Comparison of ATI-5923, a Novel Vitamin K Antagonist, With Warfarin in Patients Requiring Chronic Anticoagulation (EmbraceAC)

A Randomized, Double Blind Comparison of ATI-5923, a Novel Vitamin K Antagonist, With Warfarin in Patients Requiring Chronic Anticoagulation

The purpose of this research study is to test an experimental drug ATI-5923 vs Coumadin. The study is intended to demonstrate ATI-5923 is superior to Coumadin for keeping INR values in the desired therapeutic range. Patients who require chronic anticoagulation with one or more of the following conditions are eligible for the study: atrial fibrillation or atrial flutter, prosthetic heart valve, venous thromboembolic disease, or history of myocardial infarction or cardiomyopathy will be enrolled.

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction; Atrial Fibrillation; Atrial Flutter; Cardiomyopathy; Venous Thromboembolic Disease
• Intervention / Treatment: Drug: ATI-5923; Drug: Coumadin (warfarin)

Detailed Description

The primary study objective is to evaluate whether ATI-5923 is superior to adjusted dose warfarin in the quality of anticoagulation as measured by interpolated INR time in therapeutic range. This is a Phase II/III multi-center, randomized, stratified, double blind, parallel group, active control study comparing ATI-5923 with Coumadin in patients who require chronic, oral anticoagulation. Up to 600 patients who successfully complete all screening assessments and meet all eligibility criteria will be enrolled in the study and receive study drug treatment for 6-12 months depending on time of study entry.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Birmingham Heart Clinic, PC
    • Birmingham, Alabama, United States, 36693
      • Cardiology PC
    • Huntsville, Alabama, United States, 35801
      • The Heart Center, PC
    • Mobile, Alabama, United States, 36693
      • Mobile Heart Specialists, PC
  • Arizona
    • Tucson, Arizona, United States, 85717
      • Southwest Heart
  • California
    • Escondido, California, United States, 92025
      • Escondido Cardiology Associates
    • San Diego, California, United States, 92103
      • University of California San Diego Medical Center
    • Vista, California, United States, 92083
      • Progressive Clinical Research
  • Colorado
    • Golden, Colorado, United States, 80401
      • New West Physicians Clinical Research
  • Connecticut
    • Norwalk, Connecticut, United States, 06851
      • Cardiology Associates of Fairfield County, PC
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
    • Trumbull, Connecticut, United States, 06611
      • Cardiology Associates of Fairfield County, PC
  • Florida
    • Gainesville, Florida, United States, 32605
      • Florida Research Network, LLC
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • St. Luke's Cardiology Associates
    • Jacksonville, Florida, United States, 32207
      • Jacksonville Heart Center - Pavillon
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Heart Center - South
    • Jacksonville Beach, Florida, United States, 32250
      • Jacksonville Heart Center
    • Orlando, Florida, United States, 32806
      • Orlando Heart Center
    • Safety Harbor, Florida, United States, 34695
      • The Heart And Vascular Institute Of Florida
  • Georgia
    • Covington, Georgia, United States, 30014
      • Georgia Heart Specialists
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Heart Center, Pc
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Fox Valley Clinical Research Center, LLC
    • Normal, Illinois, United States, 61761
      • Illinois Heart and Lung Research Center
    • Winfield, Illinois, United States, 60190
      • DuPage Medical Group
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Clinical Research Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC
  • Louisiana
    • Lacombe, Louisiana, United States, 70445
      • Heart and Vascular Clinic
  • Maine
    • Auburn, Maine, United States, 04210
      • Androscoggin Cardiology Associates
  • Michigan
    • Alpena, Michigan, United States, 49707
      • Endeavor Medical Research, Plc
  • Nevada
    • Henderson, Nevada, United States, 89704
      • Steljes Cardiology, PC
  • Ohio
    • Canton, Ohio, United States, 44710
      • Cardiovascular Research Institute, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Plaza Medical Group, Pc
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Institute for Medical Research
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Internal Medicine Of Greer
  • South Dakota
    • Pierre, South Dakota, United States, 57501
      • Medical Associates Clinic, LLP
  • Texas
    • Dallas, Texas, United States, 75231
      • Cardiovascular Research Institute of Dallas
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • York Clinical Research
  • Washington
    • Burien, Washington, United States, 98166
      • Daniel Gottlieb, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with one or more of the following indications for chronic warfarin anticoagulation (the patient may either be a new candidate for anticoagulation or may already be receiving warfarin):

   1. Atrial fibrillation (paroxysmal, persistent or permanent, not due to a reversible cause, documented by ECG) or atrial flutter.
   2. A prosthetic heart valve in the aortic or mitral position that requires chronic anticoagulation.
   3. A history of venous thromboembolic disease (DVT and/or PE) requiring long term anticoagulation (> 6 months).
   4. A history of myocardial infarction or cardiomyopathy requiring anticoagulation.
   5. Currently receiving chronic warfarin therapy for another indication not listed, with Sponsor approval.
2. Male or female greater than 18 years of age.
3. Able and willing to sign IRB approved written informed consent to participate in the study.
4. Able and willing to follow instructions, to comply with protocol requirements, and to attend required study visits.

Exclusion Criteria:

1. Contraindications to anticoagulation as listed in the warfarin package insert (Appendix D), such as active bleeding or lesions at risk of bleeding such as gastric ulceration, colonic or cerebral AV malformations, cerebral or aortic aneurysms, pericarditis or endocarditis. Patients who have had recent (< 14 days from screening) surgery or invasive procedures or are about to undergo surgery or other invasive procedures, such as lumbar puncture. Patients with blood dyscrasias or inherited disorders of hemostasis. Patients with a history of hemorrhagic tendencies or prior serious hemorrhagic events such as hemorrhage within the cranium, eye, spinal cord, retroperitoneum, or gastrointestinal tract.
2. Laboratory evidence at screening of clinically significant active bleeding, such as unexplained positive occult blood in stool, or unexplained positive urinary blood that is more than trace positive for hemoglobin.
3. Concomitant use of other anticoagulant or antiplatelet agents that may add to the hemostatic burden such as clopidogrel, ticlopidine, heparin or low molecular weight heparin (LMWH), or regular use of non selective long acting NSAIDs that cannot be discontinued prior to initiating ATI 5923/warfarin dosing (daily use of 81-100 mg aspirin is allowed).
4. A life expectancy of < 1 year, end stage renal failure requiring dialysis, end stage pulmonary disease requiring home oxygen, severe heart failure (NYHA class IV).
5. Dementia, severe psychiatric disorder, or ongoing alcohol or substance abuse.
6. Laboratory screening values indicating severe anemia (Hb < 10 gm/L), thrombocytopenia (platelet count < 90,000/mcL), or active liver disease.
7. Patients with conditions that will interfere with determination of the INR using the INRatio device, i.e., hematocrit <30% or >55%. Patients with the antiphospholipid syndrome may have abnormal INR results and should not be enrolled.
8. History of non disabling ischemic stroke within the last 3 months, prior major disabling ischemic stroke, or any history of intracranial bleeding.
9. Pregnant or nursing women or women of childbearing potential who will not use adequate contraception, such as oral or implantable contraceptives, IUD, or barrier methods (IUD or condom) with spermicide.
10. Currently participating in another clinical trial at screening, treatment with an investigational drug within 30 days of the first dose of study medication, or patients who previously participated in an ATI-5923 trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1. ATI-5923; Dose adjusted ATI-5923	Drug: ATI-5923; Dose Adjusted based on INR.
ACTIVE_COMPARATOR: 2. Coumadin; Dose adjusted Coumadin (warfarin)	Drug: Coumadin (warfarin); Dose adjusted based on INR.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent of time INR is in therapeutic range after the exclusion of the first 4 weeks of treatment, using the linear interpolation method of Rosendaal(Rosendaal, 1993).	After the first month through end of study.

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of all study recorded INR values that are within the target range, after the exclusion of the INR values from the first 4 weeks of treatment	After the first month through end of study
Proportion of time patients have significant deviations from therapeutic INR range.	After the first month through end of study
A composite of the following clinically important outcome events	After the first month through end of study

Collaborators and Investigators

• Sponsor: ARYx Therapeutics

Publications and helpful links

Helpful Links

• EmbraceAC Study Site

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (ANTICIPATED): June 1, 2009
• Study Completion (ANTICIPATED): June 1, 2009

Study Registration Dates

• First Submitted: June 3, 2008
• First Submitted That Met QC Criteria: June 4, 2008
• First Posted (ESTIMATE): June 5, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): February 2, 2010
• Last Update Submitted That Met QC Criteria: February 1, 2010
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Anticoagulation; Warfarin; Coumadin; Venous thromboembolic disease; Vitamin K-dependent clotting factor inhibitor; Prosthetic heart valve; Myocardial infarction or cardiomyopathy; Patients with one or more of the following indications for chronic warfarin anticoagulation:; Atrial fibrillation (paroxysmal, persistent or permanent, not due to a reversible cause, documented by ECG) or atrial flutter;; A prosthetic heart valve in the aortic or mitral position that requires chronic anticoagulation;; A history of venous thromboembolic disease (DVT and/or PE) requiring long term anticoagulation (> 6 months);; A history of myocardial infarction or cardiomyopathy requiring anticoagulation.; Currently receiving chronic warfarin therapy for another indication not listed, with Sponsor approval.
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Arrhythmias, Cardiac; Myocardial Infarction; Infarction; Atrial Fibrillation; Thromboembolism; Cardiomyopathies; Atrial Flutter; Anticoagulants; Warfarin
• Other Study ID Numbers: CLN-505