Clinical trial NCT00691470: Comparison of ATI-5923, a Novel Vitamin K Antagonist, With Warfarin in Patients Requiring Chronic Anticoagulation
Official title: A Randomized, Double Blind Comparison of ATI-5923, a Novel Vitamin K Antagonist, With Warfarin in Patients Requiring Chronic Anticoagulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Atrial Fibrillation
Atrial Flutter
Venous Thromboembolic Disease
Myocardial Infarction
Cardiomyopathy
Keywords: 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.
Lead sponsor: ARYx Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-06-05
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: 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).
timeFrame: After the first month through end of study.
Secondary outcomes:
measure: 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
timeFrame: After the first month through end of study
measure: Proportion of time patients have significant deviations from therapeutic INR range.
timeFrame: After the first month through end of study
measure: A composite of the following clinically important outcome events
timeFrame: After the first month through end of study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Heart Clinic, PC
state: Alabama
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Huntsville
country: United States
facility: The Heart Center, PC
state: Alabama
city: Mobile
country: United States
facility: Mobile Heart Specialists, PC
state: Alabama
city: Tucson
country: United States
facility: Southwest Heart
state: Arizona
city: Escondido
country: United States
facility: Escondido Cardiology Associates
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: Vista
country: United States
facility: Progressive Clinical Research
state: California
city: Golden
country: United States
facility: New West Physicians Clinical Research
state: Colorado
city: Norwalk
country: United States
facility: Cardiology Associates of Fairfield County, PC
state: Connecticut
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Trumbull
country: United States
facility: Cardiology Associates of Fairfield County, PC
state: Connecticut
city: Gainesville
country: United States
facility: Florida Research Network, LLC
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville Beach
country: United States
facility: Jacksonville Heart Center
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Heart Center - Pavillon
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Heart Center - South
state: Florida
city: Jacksonville
country: United States
facility: St. Luke's Cardiology Associates
state: Florida
city: Orlando
country: United States
facility: Orlando Heart Center
state: Florida
city: Safety Harbor
country: United States
facility: The Heart and Vascular Institute of Florida
state: Florida
city: Covington
country: United States
facility: Georgia Heart Specialists
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Heart Center, PC
state: Georgia
city: Aurora
country: United States
facility: Fox Valley Clinical Research Center, LLC
state: Illinois
city: Normal
country: United States
facility: Illinois Heart and Lung Research Center
state: Illinois
city: Winfield
country: United States
facility: DuPage Medical Group
state: Illinois
city: Anderson
country: United States
facility: Community Clinical Research Center
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC
state: Iowa
city: Lacombe
country: United States
facility: Heart and Vascular Clinic
state: Louisiana
city: Auburn
country: United States
facility: Androscoggin Cardiology Associates
state: Maine
city: Alpena
country: United States
facility: Endeavor Medical Research, PLC
state: Michigan
city: Henderson
country: United States
facility: Steljes Cardiology, PC
state: Nevada
city: Canton
country: United States
facility: Cardiovascular Research Institute, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Plaza Medical Group, PC
state: Oklahoma
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Wynnewood
country: United States
facility: Lankenau Institute for Medical Research
state: Pennsylvania
city: Greer
country: United States
facility: Internal Medicine of Greer
state: South Carolina
city: Pierre
country: United States
facility: Medical Associates Clinic, LLP
state: South Dakota
city: Dallas
country: United States
facility: Cardiovascular Research Institute of Dallas
state: Texas
city: Norfolk
country: United States
facility: York Clinical Research
state: Virginia
city: Burien
country: United States
facility: Daniel Gottlieb, MD
state: Washington
Study officials:
References: