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

• Sponsor: ARYx Therapeutics (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT00691470
• Collaborator: (none)
• Enrollment: 600
• Locations: 41
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 14.6
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

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

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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
• Study Start Date: May 1, 2008
• Anticipated Primary Completion Date: Jun 1, 2009
• Anticipated Study Completion Date: Jun 1, 2009

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

2. Proportion of time patients have significant deviations from therapeutic INR range. [After the first month through end of study]

3. A composite of the following clinically important outcome events [After the first month through end of study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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):

2. Atrial fibrillation (paroxysmal, persistent or permanent, not due to a reversible cause, documented by ECG) or atrial flutter.

3. A prosthetic heart valve in the aortic or mitral position that requires chronic anticoagulation.

4. A history of venous thromboembolic disease (DVT and/or PE) requiring long term anticoagulation (> 6 months).

5. A history of myocardial infarction or cardiomyopathy requiring anticoagulation.

6. Currently receiving chronic warfarin therapy for another indication not listed, with Sponsor approval.

7. Male or female greater than 18 years of age.

8. Able and willing to sign IRB approved written informed consent to participate in the study.

9. 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

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Heart Clinic, PC	Birmingham	Alabama	United States	35235
2	Cardiology PC	Birmingham	Alabama	United States	36693
3	The Heart Center, PC	Huntsville	Alabama	United States	35801
4	Mobile Heart Specialists, PC	Mobile	Alabama	United States	36693
5	Southwest Heart	Tucson	Arizona	United States	85717
6	Escondido Cardiology Associates	Escondido	California	United States	92025
7	University of California San Diego Medical Center	San Diego	California	United States	92103
8	Progressive Clinical Research	Vista	California	United States	92083
9	New West Physicians Clinical Research	Golden	Colorado	United States	80401
10	Cardiology Associates of Fairfield County, PC	Norwalk	Connecticut	United States	06851
11	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
12	Cardiology Associates of Fairfield County, PC	Trumbull	Connecticut	United States	06611
13	Florida Research Network, LLC	Gainesville	Florida	United States	32605
14	Nature Coast Clinical Research	Inverness	Florida	United States	34452
15	Jacksonville Heart Center	Jacksonville Beach	Florida	United States	32250
16	Jacksonville Heart Center - Pavillon	Jacksonville	Florida	United States	32207
17	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
18	Jacksonville Heart Center - South	Jacksonville	Florida	United States	32216
19	St. Luke's Cardiology Associates	Jacksonville	Florida	United States	32216
20	Orlando Heart Center	Orlando	Florida	United States	32806
21	The Heart and Vascular Institute of Florida	Safety Harbor	Florida	United States	34695
22	Georgia Heart Specialists	Covington	Georgia	United States	30014
23	Northeast Georgia Heart Center, PC	Gainesville	Georgia	United States	30501
24	Fox Valley Clinical Research Center, LLC	Aurora	Illinois	United States	60504
25	Illinois Heart and Lung Research Center	Normal	Illinois	United States	61761
26	DuPage Medical Group	Winfield	Illinois	United States	60190
27	Community Clinical Research Center	Anderson	Indiana	United States	46011
28	McFarland Clinic PC	Ames	Iowa	United States	50010
29	Heart and Vascular Clinic	Lacombe	Louisiana	United States	70445
30	Androscoggin Cardiology Associates	Auburn	Maine	United States	04210
31	Endeavor Medical Research, PLC	Alpena	Michigan	United States	49707
32	Steljes Cardiology, PC	Henderson	Nevada	United States	89704
33	Cardiovascular Research Institute, LLC	Canton	Ohio	United States	44710
34	Plaza Medical Group, PC	Oklahoma City	Oklahoma	United States	73112
35	Bend Memorial Clinic	Bend	Oregon	United States	97701
36	Lankenau Institute for Medical Research	Wynnewood	Pennsylvania	United States	19096
37	Internal Medicine of Greer	Greer	South Carolina	United States	29651
38	Medical Associates Clinic, LLP	Pierre	South Dakota	United States	57501
39	Cardiovascular Research Institute of Dallas	Dallas	Texas	United States	75231
40	York Clinical Research	Norfolk	Virginia	United States	23510
41	Daniel Gottlieb, MD	Burien	Washington	United States	98166

Sponsors and Collaborators

• ARYx Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• EmbraceAC Study Site

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00691470
• Other Study ID Numbers: CLN-505
• First Posted: Jun 5, 2008
• Last Update Posted: Feb 2, 2010
• Last Verified: Oct 1, 2008

• Keywords provided by , ,: 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: Atrial Fibrillation; Myocardial Infarction; Cardiomyopathies; Atrial Flutter; Thromboembolism; Infarction; Warfarin

Study Results

No Results Posted as of Feb 2, 2010