ARISE - Aggressive Reduction of Inflammation Stops Events

Sponsor

AtheroGenics (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00066898

Collaborator

(none)

6,000

Enrollment

219

Locations

Duration (Months)

27.4

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the safety and efficacy of AGI-1067, as compared to placebo, in the treatment of vascular inflammation and atherosclerosis by assessing the reduction in cardiovascular events.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis Coronary Artery Disease Myocardial Infarction Unstable Angina	Drug: AGI-1067	Phase 3

Detailed Description

This study will be a Phase III multi-center, double-blind, parallel group, placebo-controlled trial involving approximately 260 study sites in the United States, Canada, South Africa and the United Kingdom. It is expected that approximately 6,600 subjects will be screened in order to randomize approximately 6,000 subjects globally (3,000 in each arm of the study). Male or female subjects with coronary artery disease are eligible to participate if they meet all required inclusion and exclusion criteria. Recruitment will be delayed for one month in subjects who have had a PCI. Subjects who have a PCI planned at the time of screening or randomization, will not be randomized until one month after this planned PCI has been conducted. All subjects who successfully complete the screening phase and meet all required inclusion and exclusion criteria will be entered into the single-blind, placebo Run-In phase of the study to establish compliance. The placebo Run-In medication will be identical to the blinded study drug used in the randomized portion of the study. After the completion of the two-week Run-In, if compliance has been adequate, study subjects will be randomized to receive AGI-1067 300 mg (two 150 mg tablets daily with a meal) or placebo (approximately equal numbers of subjects per treatment group) for a minimum of 12 months. It is anticipated that subject accrual will occur over a period of approximately 24 months and that all subjects will be followed until at least 990 subjects have experienced a primary event. Subjects will remain on drug therapy from randomization until the end of the study. It is estimated that the first subject recruited will be exposed to blinded therapy for 30 to 36 months, and the last subject will be exposed for a minimum of 6 to 12 months. For the purposes of this study one month will be equal to 28 days. The subject will be asked to return to the clinic at 1 month, 3 months, and every 3 months thereafter during the treatment phase. All clinical laboratory procedures and electrocardiographic interpretations will be performed by central laboratories. Over the study period, subjects will be followed for the occurrence of major adverse cardiovascular events. These potential endpoints will be adjudicated by an independent endpoint committee. This committee will consist of cardiologists and other physician reviewers who will be blinded to the treatment. For the purposes of safety, the trial will be monitored by an independent Data Safety Monitoring Board. This Board will consist of Cardiologists, and at least one Statistician experienced in the conduct of clinical trials. The Board will meet approximately every 6 months to review subject safety data.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Prevention

Official Title:

"Reduction of Vascular Inflammation and Coronary Atherosclerosis With AGI-1067, a V-Protectant, Reduces Cardiovascular Events in Patients With Coronary Artery Disease"

Study Start Date :

Jun 1, 2003

Study Completion Date :

Dec 1, 2006

Outcome Measures

Primary Outcome Measures

Length of time to the first occurrence of one of six adjudicated events: cardiovascular mortality, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, hospitalization for angina pectoris, or use of coronary revascularization. []

Secondary Outcome Measures

Time to first incidence of any of the following: all cause mortality, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, use of coronary revascularization, and hospitalization for unstable angina []
Time to first incidence of any of the following: cardiovascular mortality, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, and hospitalization for unstable angina []
Time to first incidence of any of the following: cardiovascular mortality, resuscitated cardiac arrest, non-fatal MI, and non-fatal stroke []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 0 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

IRB-approved informed written consent must be provided by all subjects prior to screening and study entry.

Inclusion Criteria

Informed written consent from the subject prior to Screening
Acute MI or unstable angina not less than 14 days and not more than one year prior to randomization
Male or female subjects in one of the two following groups:
Subjects with diabetes mellitus (NIDDM or IDDM) 18 years of age or older
Subjects (without diabetes mellitus) 55 years of age or older with one of the following additional risk factors:

(i) Age 60 or older (ii) Low HDL-C as evidenced by: Male: HDL-C < 40 mg/dL or Female: HDL-C < 50 mg/dL (iii) Previous Myocardial Infarction (in addition to the index event), or diagnosis of Atherosclerosis in a non-coronary vessel (e.g. history of prior stroke, presence of PVD) (iv) Prior history of CHF (Congestive Heart Failure) or ejection fraction < 40%

Females must be non-lactating and not of child bearing potential

Exclusion Criteria

Subjects who are hemodynamically or clinically unstable
Subjects who have had a PCI in the last 30 days
Subjects who have had coronary artery bypass (CABG) in the last 3 months
Subjects on a waiting list for revascularization or revascularization already planned
Current symptoms consistent with moderate or severe CHF despite medical therapy
Clinically significant valvular heart disease or Hypertrophic Obstructive Cardiomyopathy
Uncontrolled hypertension (e.g., sitting systolic BP > 180 mm Hg on antihypertensive therapy)
Known major hematologic, renal, hepatic, metabolic, gastrointestinal or endocrine dysfunction
Subjects taking and requiring continued therapy with drugs known to significantly prolong the QT interval (this will not include drugs associated with minor effect on the QT interval of less than 15 msec.)
Life-threatening illness where the subject is not expected to survive for 2 years or any history of cancer or malignancy within the past 5 years except for basal cell carcinoma or squamous cell carcinoma of the skin
A history of intolerance to probucol (Lorelco™)
Unreliability as a study participant based on the Investigator's (or designee's) knowledge of the subject (e.g., alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
Participation in any investigational drug study within 30 days prior to study entry, or expectation to participate in any other investigational drug study during the course of the ARISE study.
Previous participation in a study involving AGI-1067

Contacts and Locations

Locations

	Site	City	State	Country
1	Cardiovascular Associates	Birmingham	Alabama	United States
2	Univ of Alabama at Birmingham	Birmingham	Alabama	United States
3	The Heart Center/Oracle Research	Huntsville	Alabama	United States
4	Tri City Cardiology Consultants	Mesa	Arizona	United States
5	Tri-City Cardiology Consultants	Mesa	Arizona	United States
6	Hope Research Institute	Phoenix	Arizona	United States
7	Lovelace Scientific Resources	Phoenix	Arizona	United States
8	Sonoran Health Specialists	Scottsdale	Arizona	United States
9	Capitol Interventional Cardiology	Carmichael	California	United States
10	Escondido Cardiology	Escondido	California	United States
11	Merced Heart Associates	Merced	California	United States
12	Orange County Research Cntr	Orange	California	United States
13	ARI Clinical Trials	Redondo Beach	California	United States
14	Radiant Research	Santa Rosa	California	United States
15	Pikes Peak Cardiology	Colorado Springs	Colorado	United States
16	Aurora Denver Cardiololgy Associates	Denver	Colorado	United States
17	Heart and Vascular Clinic N CO	Fort Collins	Colorado	United States
18	Connecticut Clinical Research	Bridgeport	Connecticut	United States
19	Cardiac Specialists, PC	Trumbull	Connecticut	United States
20	Christiana Care Health Svcs	Newark	Delaware	United States
21	Clinical Research of West Florida, Inc.	Clearwater	Florida	United States
22	SW Florida Heart Group	Fort Myers	Florida	United States
23	Univ of Florida, Cardiology	Gainesville	Florida	United States
24	Jacksonville Heart Center	Jacksonville Beach	Florida	United States
25	Diagnostic Cardiology	Jacksonville	Florida	United States
26	Jacksonville Cntr Clin Research	Jacksonville	Florida	United States
27	Watson Clinic LLP	Lakeland	Florida	United States
28	Cardiovascular Research Center of South Florida	Miami	Florida	United States
29	Orlando Heart Cntr	Orlando	Florida	United States
30	Cardiovascular Cntr of Sarasota	Sarasota	Florida	United States
31	The Broward Heart Group	Tamarac	Florida	United States
32	Clinical Research of West Florida, Inc.	Tampa	Florida	United States
33	Crawford Long Hospital	Atlanta	Georgia	United States
34	Emory University Hospital	Atlanta	Georgia	United States
35	Fuqua Hrt Cntr Piedmont Hosp	Atlanta	Georgia	United States
36	Harbin Clinic	Rome	Georgia	United States
37	Idaho Cardiology Associates	Boise	Idaho	United States
38	Heart Care Research Foundation	Blue Island	Illinois	United States
39	Peryam and Kroll Healthcare	Chicago	Illinois	United States
40	Heartcare Midwest Heart Inst	Peoria	Illinois	United States
41	The Heart Group	Evansville	Indiana	United States
42	Welborn Clinic Research Center	Evansville	Indiana	United States
43	Parkview Hospital	Fort Wayne	Indiana	United States
44	Care Group St. Vincent Hosp of IN	Indianapolis	Indiana	United States
45	Research Inst of Middle America	Jeffersonville	Indiana	United States
46	Iowa Heart Center	Des Moines	Iowa	United States
47	Univ of IA College of Medicine	Iowa City	Iowa	United States
48	Research Inst of Kansas Inc	Wichita	Kansas	United States
49	Cardiovascular Associates	Louisville	Kentucky	United States
50	Louisiana Heart Center	Chalmette	Louisiana	United States
51	The Office of Dr. Richard Gilmore	Lake Charles	Louisiana	United States
52	Heart Clinic of Louisiana	Marrero	Louisiana	United States
53	Cardiovascular Inst of the South	Morgan City	Louisiana	United States
54	Cardiovascular Inst of the South	New Iberia	Louisiana	United States
55	Louisiana Clinical Trials	New Orleans	Louisiana	United States
56	Tulane Univ Medical Center	New Orleans	Louisiana	United States
57	Medical Research Institute	Slidell	Louisiana	United States
58	Cardiovascular Inst of South	Thibodaux	Louisiana	United States
59	Androscoggin Cardiology	Auburn	Maine	United States
60	Midatlantic Cardiovascular Associates	Baltimore	Maryland	United States
61	Midatlantic Cardiovascular	Baltimore	Maryland	United States
62	Midatlantic Cardiovascular	Bel Air	Maryland	United States
63	Patuxent Medical Group	Columbia	Maryland	United States
64	MD Med Research Ong Med Cntr	Oxon Hill	Maryland	United States
65	Midatlantic Cardiovascular	Towson	Maryland	United States
66	Midatlantic Cardiovascular	Westminster	Maryland	United States
67	Compass Medical Associates	Abington	Massachusetts	United States
68	Gary Brockington, MD	Boston	Massachusetts	United States
69	Lahey Clinic Med Cntr	Burlington	Massachusetts	United States
70	Pentucket Med Assoc Inc	Haverhill	Massachusetts	United States
71	Charles River Med Associates	Natick	Massachusetts	United States
72	Professional Clinical Research	Cadillac	Michigan	United States
73	Borgess Medical Center	Kalamazoo	Michigan	United States
74	The Office of Dr. Keith Pierce	Livonia	Michigan	United States
75	Beaumont Medical Office Bldg	Royal Oak	Michigan	United States
76	Michigan Heart Group	Troy	Michigan	United States
77	St Paul Heart Clinic	St Paul	Minnesota	United States
78	N'Touch Research	Kansas City	Missouri	United States
79	St Louis Univ Div Solutions	St Louis	Missouri	United States
80	St Louis Univ Hospital	St Louis	Missouri	United States
81	Washington Univ School of Med	St Louis	Missouri	United States
82	Nebraska Heart Institute	Lincoln	Nebraska	United States
83	Creighton Cardiac Center	Omaha	Nebraska	United States
84	Nebraska Heart Institute	Papillion	Nebraska	United States
85	Cardiovascular Assoc of Delaware Valley	Elmer	New Jersey	United States
86	Cardiovascular Associates of the Delaware Valley	Haddon Heights	New Jersey	United States
87	SUNY Downstate Health Science Ctr	Brooklyn	New York	United States
88	St Vincent's Med Cntr NY	New York	New York	United States
89	SUNY Upstate Medical Univ	Syracuse	New York	United States
90	Syracuse Preventive Cardiology	Syracuse	New York	United States
91	Buffalo Cardiology and Pulmonary Associates	Williamsville	New York	United States
92	Mid Carolina Cardiology Research Div	Charlotte	North Carolina	United States
93	City Cardiology Associates	Akron	Ohio	United States
94	Lindner Clinical Trial Center	Cincinnati	Ohio	United States
95	New Horizons Clinical Research	Cincinnati	Ohio	United States
96	Sterling Research Group	Cincinnati	Ohio	United States
97	North Ohio Heart Center	Sandusky	Ohio	United States
98	Bluestem Cardiology	Bartlesville	Oklahoma	United States
99	COR Clinical Research, LLC	Oklahoma City	Oklahoma	United States
100	Castlerock Clinical Research Consultants	Tulsa	Oklahoma	United States
101	The Heart Care Group	Allentown	Pennsylvania	United States
102	Tri-State Medical Group	Beaver	Pennsylvania	United States
103	Geisinger Medical Center	Danville	Pennsylvania	United States
104	Kandra, Fierer, Kuskin Associates	Harrisburg	Pennsylvania	United States
105	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States
106	Banksville Medical	Pittsburgh	Pennsylvania	United States
107	Rhode Island Cardiovascular Group	Woonsocket	Rhode Island	United States
108	Charleston Cardiology	Charleston	South Carolina	United States
109	Internal Medicine of Greer	Greer	South Carolina	United States
110	Alpha Clinical Research	Clarksville	Tennessee	United States
111	Cardiovascular Research Foundation	Knoxville	Tennessee	United States
112	Amarillo Heart Clinical Research Institute	Amarillo	Texas	United States
113	Pharma Tex Research	Amarillo	Texas	United States
114	Austin Heart PA	Austin	Texas	United States
115	Southeast Texas Cardiology Associates II	Beaumont	Texas	United States
116	Clinical Cardiovascular Research Cntr	Dallas	Texas	United States
117	The Methodist Hospital	Houston	Texas	United States
118	Research Clinic	Nassau Bay	Texas	United States
119	Sioco Cardiology, PA	San Antonio	Texas	United States
120	Heart Center	Salt Lake City	Utah	United States
121	IHC Health Services	Salt Lake City	Utah	United States
122	DUCCS Research of S Boston	South Boston	Virginia	United States
123	Daniel Gottlieb MD PS	Burien	Washington	United States
124	U of WA NW Lipid Research Cntr	Seattle	Washington	United States
125	Appleton Heart Inst	Appleton	Wisconsin	United States
126	Wisconsin Center for Clinical Research	Elkhorn	Wisconsin	United States
127	Medical College of Wisconsin	Milwaukee	Wisconsin	United States
128	Allegiance Research Specialists	Wauwatosa	Wisconsin	United States
129	Foothills Hospital Cardiology Div	Calgary	Alberta	Canada
130	Royal Alexandra Hospital	Edmonton	Alberta	Canada
131	West Coast Cardiology Research	New Westminster	British Columbia	Canada
132	Vancouver General Hospital	Vancouver	British Columbia	Canada
133	Health Sciences Centre	Winnipeg	Manitoba	Canada
134	St Boniface General Hospital	Winnipeg	Manitoba	Canada
135	Health Sciences Centre Div of Cardiology	St. Johns	Newfoundland and Labrador	Canada
136	Queen Elizabeth Health Sciences Centre	Halifax	Nova Scotia	Canada
137	Halton Heart Institute	Burlington	Ontario	Canada
138	St Joseph Health Care Hamilton	Hamilton	Ontario	Canada
139	Kingston Heart Clinic	Kingston	Ontario	Canada
140	London Health Sci Cntr Site	London	Ontario	Canada
141	Mount St. Joseph's	London	Ontario	Canada
142	Newmarket Cardiology Research	Newmarket	Ontario	Canada
143	Heart Care Research	Oshawa	Ontario	Canada
144	Ottawa Cardiovascular Center	Ottawa	Ontario	Canada
145	Vexler Health Services	Ottawa	Ontario	Canada
146	The Office of Dr. Syan Gurcharan	Sudbury	Ontario	Canada
147	Cliks Medical Research	Thunder Bay	Ontario	Canada
148	Thunder Bay Regional Health Science Ctr	Thunder Bay	Ontario	Canada
149	Mount Sinai Hospital	Toronto	Ontario	Canada
150	Sunnybrook and Women's College	Toronto	Ontario	Canada
151	University Health Network - Toronto Western Hosp	Toronto	Ontario	Canada
152	CMGC-GRID Complexe Hosp	Chicoutimi	Quebec	Canada
153	Q & T Research Outaouais	Gatineau	Quebec	Canada
154	Recherches Cliniques Theradev	Granby	Quebec	Canada
155	The Office of Dr. Jean-Robert Timothee	Greenfield Park	Quebec	Canada
156	ViaCar Recherche Clinique	Greenfield Park	Quebec	Canada
157	Hosp Regional de Lanaudiere	Joliette	Quebec	Canada
158	Cite de la Sante de Laval	Laval	Quebec	Canada
159	Clinique de Cardiologie de Levis	Levis	Quebec	Canada
160	Medicayeb, Inc.	Longueuil	Quebec	Canada
161	ViaCar Recherche Clinique Inc.	Longueuil	Quebec	Canada
162	CHUM Hopital Notre Dame	Montreal	Quebec	Canada
163	CUSM Montreal General Hosp	Montreal	Quebec	Canada
164	Hopital du Sacre Coeur De Montreal	Montreal	Quebec	Canada
165	Maisonneuve Rosemont Hosp	Montreal	Quebec	Canada
166	McGill Univ Health Cntr	Montreal	Quebec	Canada
167	Medi-Recherche Inc.	Montreal	Quebec	Canada
168	Montreal Heart Institute	Montreal	Quebec	Canada
169	Recherches Clinicar	Quebec City	Quebec	Canada
170	Reseau Sante Richelieu Yamaska	Saint Hyacinthe	Quebec	Canada
171	Zoom International	Saint Jerome	Quebec	Canada
172	Neufort Inc.	Saint-Lambert	Quebec	Canada
173	London Clinical Research	Sherbrooke	Quebec	Canada
174	Cntr Hospital Beauce Etchemin	St. George	Quebec	Canada
175	Hopital du Haut-Richelieu	St.-Jean sur Richelieu	Quebec	Canada
176	Laval Hospital Pavillion 2U	Ste-Foy	Quebec	Canada
177	Cntr Hospitalier Pierre Le Gardeur	Terrebonne	Quebec	Canada
178	Centre Hospitalier de Val d'Or	Val d'Or	Quebec	Canada
179	Societe des internistes Bois Fran	Victoriaville	Quebec	Canada
180	Pasqua Hosp Coronary Care Unit	Regina	Saskatchewan	Canada
181	Royal University Hospital	Saskatoon	Saskatchewan	Canada
182	Saskatoon Medical Specialists	Saskatoon	Saskatchewan	Canada
183	Dr. Johann Viljoen	Bloemfontein	BLM	South Africa
184	Fichmed 5, Rosepark Hospital	Bloemfontein	BLM	South Africa
185	Universitas Hospital	Bloemfontein	BLM	South Africa
186	228 Panorama Medi Clinic	Panorama	CT	South Africa
187	Panorama Medical Clinic	Panorama	CT	South Africa
188	Tygerberg Hospital	Parow	CT	South Africa
189	Vincent Pallotti Hospital	Pinelands	CT	South Africa
190	Vergelegen Medical Clinic	Somerset West	CT	South Africa
191	Chatsmed Garden Hospital	Chatsworth	DBN	South Africa
192	Chatsmed Hospital	Chatsworth	DBN	South Africa
193	403 Maxwell Centre	Durban	DBN	South Africa
194	United House	Fordsburg	JHB	South Africa
195	The Boulders Shopping Center	Halfway House	JHB	South Africa
196	Mulbarton Medical Center	Mulbarton	JHB	South Africa
197	Olivedale Clinic	Olivedale	JHB	South Africa
198	Sunninghill Hospital	Sunninghill,	JHB	South Africa
199	Pretoria Heart Hospital	Arcadia	PTA	South Africa
200	Unitas Hospital	Lyttelton Centurion	PTA	South Africa
201	Wilgers Medical Consortium	The Willows	PTA	South Africa
202	King's College Hospital NHS Trust	London	England	United Kingdom
203	Barking, Havering & Redbridge Hospital NHS Trust	Romford	Essex	United Kingdom
204	Grampian University Hospitals NHS Trust	Aberdeen		United Kingdom
205	Sandwell & West Birmingham City Hospital NHS Trust	Birmingham		United Kingdom
206	Papworth Hospital NHS Trust	Cambridge		United Kingdom
207	The Lothian University Hospitals NHS Trust	Edinburgh		United Kingdom
208	North Glasglow University Hospitals NHS Trust	Glasglow		United Kingdom
209	South Glasglow University Hospital NHS Trust	Glasglow		United Kingdom
210	Western Infirmary Glaglow	Glasglow		United Kingdom
211	The Leeds Teaching Hospitals NHS Trust	Leeds		United Kingdom
212	University Hospitals of Leicester NHS Trust	Leicester		United Kingdom
213	Liverpool NHS Trust	Liverpool		United Kingdom
214	South Manchester University Hospitals NHS Trust	Manchester		United Kingdom
215	Argyll & Clyde NHS Trust	Paisley		United Kingdom
216	Sheffield Teaching Hospitals NHS Trust	Sheffield		United Kingdom
217	Forth Valley Acute Hospitals NHS Trust	Stirling		United Kingdom
218	University Hospitals of North Staffordshire NHS Trust	Stok-on-Trent		United Kingdom
219	Mid Yorkshire Hospitals	Wakefield		United Kingdom

Sponsors and Collaborators

AtheroGenics

Investigators

Study Chair: Marc A Pfeffer, MD, Cardiovascular Division Brigham and Women's Hospital
Study Chair: Jean-Claude Tardif, MD, Montreal Heart Institute
Principal Investigator: John McMurray, MD, Western Infirmary
Principal Investigator: Eric Klug, MD, Independent Medical Practitioner - South Africa