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

Atrial Fibrillation Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00691470
• Other study ID #: CLN-505
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: June 3, 2008
• Last updated: February 1, 2010
• Start date: May 2008
• Est. completion date: June 2009

Study information

• Verified date: October 2008
• Source: ARYx Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Flutter
• Cardiomyopathies
• Cardiomyopathy
• Infarction
• Myocardial Infarction
• Thromboembolism
• Venous Thromboembolic Disease

Intervention

Drug:
• ATI-5923
Dose Adjusted based on INR.
• Coumadin (warfarin)
Dose adjusted based on INR.

Locations

Country	Name	City	State
United States	Endeavor Medical Research, PLC	Alpena	Michigan
United States	McFarland Clinic PC	Ames	Iowa
United States	Community Clinical Research Center	Anderson	Indiana
United States	Androscoggin Cardiology Associates	Auburn	Maine
United States	Fox Valley Clinical Research Center, LLC	Aurora	Illinois
United States	Bend Memorial Clinic	Bend	Oregon
United States	Birmingham Heart Clinic, PC	Birmingham	Alabama
United States	Cardiology PC	Birmingham	Alabama
United States	Daniel Gottlieb, MD	Burien	Washington
United States	Cardiovascular Research Institute, LLC	Canton	Ohio
United States	Georgia Heart Specialists	Covington	Georgia
United States	Cardiovascular Research Institute of Dallas	Dallas	Texas
United States	Escondido Cardiology Associates	Escondido	California
United States	Florida Research Network, LLC	Gainesville	Florida
United States	Northeast Georgia Heart Center, PC	Gainesville	Georgia
United States	New West Physicians Clinical Research	Golden	Colorado
United States	Internal Medicine of Greer	Greer	South Carolina
United States	Steljes Cardiology, PC	Henderson	Nevada
United States	The Heart Center, PC	Huntsville	Alabama
United States	Nature Coast Clinical Research	Inverness	Florida
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Jacksonville Heart Center - Pavillon	Jacksonville	Florida
United States	Jacksonville Heart Center - South	Jacksonville	Florida
United States	St. Luke's Cardiology Associates	Jacksonville	Florida
United States	Jacksonville Heart Center	Jacksonville Beach	Florida
United States	Heart and Vascular Clinic	Lacombe	Louisiana
United States	Mobile Heart Specialists, PC	Mobile	Alabama
United States	York Clinical Research	Norfolk	Virginia
United States	Illinois Heart and Lung Research Center	Normal	Illinois
United States	Cardiology Associates of Fairfield County, PC	Norwalk	Connecticut
United States	Plaza Medical Group, PC	Oklahoma City	Oklahoma
United States	Orlando Heart Center	Orlando	Florida
United States	Medical Associates Clinic, LLP	Pierre	South Dakota
United States	The Heart and Vascular Institute of Florida	Safety Harbor	Florida
United States	University of California San Diego Medical Center	San Diego	California
United States	Stamford Therapeutics Consortium	Stamford	Connecticut
United States	Cardiology Associates of Fairfield County, PC	Trumbull	Connecticut
United States	Southwest Heart	Tucson	Arizona
United States	Progressive Clinical Research	Vista	California
United States	DuPage Medical Group	Winfield	Illinois
United States	Lankenau Institute for Medical Research	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
ARYx Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	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	Yes
Secondary	Proportion of time patients have significant deviations from therapeutic INR range.		After the first month through end of study	Yes
Secondary	A composite of the following clinically important outcome events		After the first month through end of study	Yes