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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by ARYx Therapeutics.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
ARYx Therapeutics
ClinicalTrials.gov Identifier:
NCT00691470
First received: June 3, 2008
Last updated: February 1, 2010
Last verified: October 2008
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Atrial Flutter
Venous Thromboembolic Disease
Myocardial Infarction
Cardiomyopathy
Drug: ATI-5923
Drug: Coumadin (warfarin)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Comparison of ATI-5923, a Novel Vitamin K Antagonist, With Warfarin in Patients Requiring Chronic Anticoagulation

Resource links provided by NLM:


Further study details as provided by ARYx Therapeutics:

Primary Outcome Measures:
  • 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). [ Time Frame: After the first month through end of study. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: After the first month through end of study ] [ Designated as safety issue: Yes ]
  • Proportion of time patients have significant deviations from therapeutic INR range. [ Time Frame: After the first month through end of study ] [ Designated as safety issue: Yes ]
  • A composite of the following clinically important outcome events [ Time Frame: After the first month through end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: May 2008
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00691470

  Show 41 Study Locations
Sponsors and Collaborators
ARYx Therapeutics
  More Information

No publications provided

Responsible Party: Daniel Canafax, ARYx Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT00691470     History of Changes
Other Study ID Numbers: CLN-505
Study First Received: June 3, 2008
Last Updated: February 1, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by ARYx Therapeutics:
Anticoagulation
Vitamin K-dependent clotting factor inhibitor
Coumadin
Warfarin
Atrial fibrillation
Prosthetic heart valve
Venous thromboembolic disease
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:
Myocardial Infarction
Infarction
Atrial Fibrillation
Cardiomyopathies
Atrial Flutter
Thromboembolism
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Ischemia
Pathologic Processes
Necrosis
Arrhythmias, Cardiac
Embolism and Thrombosis
Thrombosis
Vitamins
Vitamin K
Warfarin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014