ARISE – Aggressive Reduction of Inflammation Stops Events

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00066898
• Other study ID #: AGI-1067/042
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 6, 2003
• Last updated: September 29, 2006
• Start date: June 2003
• Est. completion date: December 2006

Study information

• Verified date: September 2006
• Source: AtheroGenics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCanada: Health CanadaSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6000
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

A. Inclusion Criteria

1. Informed written consent from the subject prior to Screening

2. Acute MI or unstable angina not less than 14 days and not more than one year prior to randomization

3. Male or female subjects in one of the two following groups:

1. Subjects with diabetes mellitus (NIDDM or IDDM) 18 years of age or older

2. 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%

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

B. Exclusion Criteria

1. Subjects who are hemodynamically or clinically unstable

2. Subjects who have had a PCI in the last 30 days

3. Subjects who have had coronary artery bypass (CABG) in the last 3 months

4. Subjects on a waiting list for revascularization or revascularization already planned

5. Current symptoms consistent with moderate or severe CHF despite medical therapy

6. Clinically significant valvular heart disease or Hypertrophic Obstructive Cardiomyopathy

7. Uncontrolled hypertension (e.g., sitting systolic BP > 180 mm Hg on antihypertensive therapy)

8. Known major hematologic, renal, hepatic, metabolic, gastrointestinal or endocrine dysfunction

9. 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.)

10. 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

11. A history of intolerance to probucol (Lorelco™)

12. 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)

13. 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.

14. Previous participation in a study involving AGI-1067

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Angina, Unstable
• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Infarction
• Myocardial Ischemia
• Unstable Angina

Intervention

Drug:
• AGI-1067

Locations

Country	Name	City	State
Canada	Halton Heart Institute	Burlington	Ontario
Canada	Foothills Hospital Cardiology Div	Calgary	Alberta
Canada	CMGC-GRID Complexe Hosp	Chicoutimi	Quebec
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	Q & T Research Outaouais	Gatineau	Quebec
Canada	Recherches Cliniques Theradev	Granby	Quebec
Canada	The Office of Dr. Jean-Robert Timothee	Greenfield Park	Quebec
Canada	ViaCar Recherche Clinique	Greenfield Park	Quebec
Canada	Queen Elizabeth Health Sciences Centre	Halifax	Nova Scotia
Canada	St Joseph Health Care Hamilton	Hamilton	Ontario
Canada	Hosp Regional de Lanaudiere	Joliette	Quebec
Canada	Kingston Heart Clinic	Kingston	Ontario
Canada	Cite de la Sante de Laval	Laval	Quebec
Canada	Clinique de Cardiologie de Levis	Levis	Quebec
Canada	London Health Sci Cntr Site	London	Ontario
Canada	Mount St. Joseph's	London	Ontario
Canada	Medicayeb, Inc.	Longueuil	Quebec
Canada	ViaCar Recherche Clinique Inc.	Longueuil	Quebec
Canada	CHUM Hopital Notre Dame	Montreal	Quebec
Canada	CUSM Montreal General Hosp	Montreal	Quebec
Canada	Hopital du Sacre Coeur De Montreal	Montreal	Quebec
Canada	Maisonneuve Rosemont Hosp	Montreal	Quebec
Canada	McGill Univ Health Cntr	Montreal	Quebec
Canada	Medi-Recherche Inc.	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	West Coast Cardiology Research	New Westminster	British Columbia
Canada	Newmarket Cardiology Research	Newmarket	Ontario
Canada	Heart Care Research	Oshawa	Ontario
Canada	Ottawa Cardiovascular Center	Ottawa	Ontario
Canada	Vexler Health Services	Ottawa	Ontario
Canada	Recherches Clinicar	Quebec City	Quebec
Canada	Pasqua Hosp Coronary Care Unit	Regina	Saskatchewan
Canada	Reseau Sante Richelieu Yamaska	Saint Hyacinthe	Quebec
Canada	Zoom International	Saint Jerome	Quebec
Canada	Neufort Inc.	Saint-Lambert	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Saskatoon Medical Specialists	Saskatoon	Saskatchewan
Canada	London Clinical Research	Sherbrooke	Quebec
Canada	Cntr Hospital Beauce Etchemin	St. George	Quebec
Canada	Health Sciences Centre Div of Cardiology	St. Johns	Newfoundland and Labrador
Canada	Hopital du Haut-Richelieu	St.-Jean sur Richelieu	Quebec
Canada	Laval Hospital Pavillion 2U	Ste-Foy	Quebec
Canada	The Office of Dr. Syan Gurcharan	Sudbury	Ontario
Canada	Cntr Hospitalier Pierre Le Gardeur	Terrebonne	Quebec
Canada	Cliks Medical Research	Thunder Bay	Ontario
Canada	Thunder Bay Regional Health Science Ctr	Thunder Bay	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook and Women's College	Toronto	Ontario
Canada	University Health Network - Toronto Western Hosp	Toronto	Ontario
Canada	Centre Hospitalier de Val d'Or	Val d'Or	Quebec
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Societe des internistes Bois Fran	Victoriaville	Quebec
Canada	Health Sciences Centre	Winnipeg	Manitoba
Canada	St Boniface General Hospital	Winnipeg	Manitoba
South Africa	Pretoria Heart Hospital	Arcadia	PTA
South Africa	Dr. Johann Viljoen	Bloemfontein	BLM
South Africa	Fichmed 5, Rosepark Hospital	Bloemfontein	BLM
South Africa	Universitas Hospital	Bloemfontein	BLM
South Africa	Chatsmed Garden Hospital	Chatsworth	DBN
South Africa	Chatsmed Hospital	Chatsworth	DBN
South Africa	403 Maxwell Centre	Durban	DBN
South Africa	United House	Fordsburg	JHB
South Africa	The Boulders Shopping Center	Halfway House	JHB
South Africa	Unitas Hospital	Lyttelton Centurion	PTA
South Africa	Mulbarton Medical Center	Mulbarton	JHB
South Africa	Olivedale Clinic	Olivedale	JHB
South Africa	228 Panorama Medi Clinic	Panorama	CT
South Africa	Panorama Medical Clinic	Panorama	CT
South Africa	Tygerberg Hospital	Parow	CT
South Africa	Vincent Pallotti Hospital	Pinelands	CT
South Africa	Vergelegen Medical Clinic	Somerset West	CT
South Africa	Sunninghill Hospital	Sunninghill,	JHB
South Africa	Wilgers Medical Consortium	The Willows	PTA
United Kingdom	Grampian University Hospitals NHS Trust	Aberdeen
United Kingdom	Sandwell & West Birmingham City Hospital NHS Trust	Birmingham
United Kingdom	Papworth Hospital NHS Trust	Cambridge
United Kingdom	The Lothian University Hospitals NHS Trust	Edinburgh
United Kingdom	North Glasglow University Hospitals NHS Trust	Glasglow
United Kingdom	South Glasglow University Hospital NHS Trust	Glasglow
United Kingdom	Western Infirmary Glaglow	Glasglow
United Kingdom	The Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester
United Kingdom	Liverpool NHS Trust	Liverpool
United Kingdom	King's College Hospital NHS Trust	London	England
United Kingdom	South Manchester University Hospitals NHS Trust	Manchester
United Kingdom	Argyll & Clyde NHS Trust	Paisley
United Kingdom	Barking, Havering & Redbridge Hospital NHS Trust	Romford	Essex
United Kingdom	Sheffield Teaching Hospitals NHS Trust	Sheffield
United Kingdom	Forth Valley Acute Hospitals NHS Trust	Stirling
United Kingdom	University Hospitals of North Staffordshire NHS Trust	Stok-on-Trent
United Kingdom	Mid Yorkshire Hospitals	Wakefield
United States	Compass Medical Associates	Abington	Massachusetts
United States	City Cardiology Associates	Akron	Ohio
United States	The Heart Care Group	Allentown	Pennsylvania
United States	Amarillo Heart Clinical Research Institute	Amarillo	Texas
United States	Pharma Tex Research	Amarillo	Texas
United States	Appleton Heart Inst	Appleton	Wisconsin
United States	Crawford Long Hospital	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Fuqua Hrt Cntr Piedmont Hosp	Atlanta	Georgia
United States	Androscoggin Cardiology	Auburn	Maine
United States	Austin Heart PA	Austin	Texas
United States	Midatlantic Cardiovascular	Baltimore	Maryland
United States	Midatlantic Cardiovascular Associates	Baltimore	Maryland
United States	Bluestem Cardiology	Bartlesville	Oklahoma
United States	Southeast Texas Cardiology Associates II	Beaumont	Texas
United States	Tri-State Medical Group	Beaver	Pennsylvania
United States	Midatlantic Cardiovascular	Bel Air	Maryland
United States	Cardiovascular Associates	Birmingham	Alabama
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Heart Care Research Foundation	Blue Island	Illinois
United States	Idaho Cardiology Associates	Boise	Idaho
United States	Gary Brockington, MD	Boston	Massachusetts
United States	Connecticut Clinical Research	Bridgeport	Connecticut
United States	SUNY Downstate Health Science Ctr	Brooklyn	New York
United States	Daniel Gottlieb MD PS	Burien	Washington
United States	Lahey Clinic Med Cntr	Burlington	Massachusetts
United States	Professional Clinical Research	Cadillac	Michigan
United States	Capitol Interventional Cardiology	Carmichael	California
United States	Louisiana Heart Center	Chalmette	Louisiana
United States	Charleston Cardiology	Charleston	South Carolina
United States	Mid Carolina Cardiology Research Div	Charlotte	North Carolina
United States	Peryam and Kroll Healthcare	Chicago	Illinois
United States	Lindner Clinical Trial Center	Cincinnati	Ohio
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Sterling Research Group	Cincinnati	Ohio
United States	Alpha Clinical Research	Clarksville	Tennessee
United States	Clinical Research of West Florida, Inc.	Clearwater	Florida
United States	Pikes Peak Cardiology	Colorado Springs	Colorado
United States	Patuxent Medical Group	Columbia	Maryland
United States	Clinical Cardiovascular Research Cntr	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Aurora Denver Cardiololgy Associates	Denver	Colorado
United States	Iowa Heart Center	Des Moines	Iowa
United States	Wisconsin Center for Clinical Research	Elkhorn	Wisconsin
United States	Cardiovascular Assoc of Delaware Valley	Elmer	New Jersey
United States	Escondido Cardiology	Escondido	California
United States	The Heart Group	Evansville	Indiana
United States	Welborn Clinic Research Center	Evansville	Indiana
United States	Heart and Vascular Clinic N CO	Fort Collins	Colorado
United States	SW Florida Heart Group	Fort Myers	Florida
United States	Parkview Hospital	Fort Wayne	Indiana
United States	Univ of Florida, Cardiology	Gainesville	Florida
United States	Internal Medicine of Greer	Greer	South Carolina
United States	Cardiovascular Associates of the Delaware Valley	Haddon Heights	New Jersey
United States	Kandra, Fierer, Kuskin Associates	Harrisburg	Pennsylvania
United States	Pentucket Med Assoc Inc	Haverhill	Massachusetts
United States	The Methodist Hospital	Houston	Texas
United States	The Heart Center/Oracle Research	Huntsville	Alabama
United States	Care Group St. Vincent Hosp of IN	Indianapolis	Indiana
United States	Univ of IA College of Medicine	Iowa City	Iowa
United States	Diagnostic Cardiology	Jacksonville	Florida
United States	Jacksonville Cntr Clin Research	Jacksonville	Florida
United States	Jacksonville Heart Center	Jacksonville Beach	Florida
United States	Research Inst of Middle America	Jeffersonville	Indiana
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	N'Touch Research	Kansas City	Missouri
United States	Cardiovascular Research Foundation	Knoxville	Tennessee
United States	The Office of Dr. Richard Gilmore	Lake Charles	Louisiana
United States	Watson Clinic LLP	Lakeland	Florida
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	The Office of Dr. Keith Pierce	Livonia	Michigan
United States	Cardiovascular Associates	Louisville	Kentucky
United States	Heart Clinic of Louisiana	Marrero	Louisiana
United States	Merced Heart Associates	Merced	California
United States	Tri City Cardiology Consultants	Mesa	Arizona
United States	Tri-City Cardiology Consultants	Mesa	Arizona
United States	Cardiovascular Research Center of South Florida	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Cardiovascular Inst of the South	Morgan City	Louisiana
United States	Research Clinic	Nassau Bay	Texas
United States	Charles River Med Associates	Natick	Massachusetts
United States	Cardiovascular Inst of the South	New Iberia	Louisiana
United States	Louisiana Clinical Trials	New Orleans	Louisiana
United States	Tulane Univ Medical Center	New Orleans	Louisiana
United States	St Vincent's Med Cntr NY	New York	New York
United States	Christiana Care Health Svcs	Newark	Delaware
United States	COR Clinical Research, LLC	Oklahoma City	Oklahoma
United States	Creighton Cardiac Center	Omaha	Nebraska
United States	Orange County Research Cntr	Orange	California
United States	Orlando Heart Cntr	Orlando	Florida
United States	MD Med Research Ong Med Cntr	Oxon Hill	Maryland
United States	Nebraska Heart Institute	Papillion	Nebraska
United States	Heartcare Midwest Heart Inst	Peoria	Illinois
United States	Hope Research Institute	Phoenix	Arizona
United States	Lovelace Scientific Resources	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Banksville Medical	Pittsburgh	Pennsylvania
United States	ARI Clinical Trials	Redondo Beach	California
United States	Harbin Clinic	Rome	Georgia
United States	Beaumont Medical Office Bldg	Royal Oak	Michigan
United States	Heart Center	Salt Lake City	Utah
United States	IHC Health Services	Salt Lake City	Utah
United States	Sioco Cardiology, PA	San Antonio	Texas
United States	North Ohio Heart Center	Sandusky	Ohio
United States	Radiant Research	Santa Rosa	California
United States	Cardiovascular Cntr of Sarasota	Sarasota	Florida
United States	Sonoran Health Specialists	Scottsdale	Arizona
United States	U of WA NW Lipid Research Cntr	Seattle	Washington
United States	Medical Research Institute	Slidell	Louisiana
United States	DUCCS Research of S Boston	South Boston	Virginia
United States	St Louis Univ Div Solutions	St Louis	Missouri
United States	St Louis Univ Hospital	St Louis	Missouri
United States	Washington Univ School of Med	St Louis	Missouri
United States	St Paul Heart Clinic	St Paul	Minnesota
United States	SUNY Upstate Medical Univ	Syracuse	New York
United States	Syracuse Preventive Cardiology	Syracuse	New York
United States	The Broward Heart Group	Tamarac	Florida
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	Cardiovascular Inst of South	Thibodaux	Louisiana
United States	Midatlantic Cardiovascular	Towson	Maryland
United States	Michigan Heart Group	Troy	Michigan
United States	Cardiac Specialists, PC	Trumbull	Connecticut
United States	Castlerock Clinical Research Consultants	Tulsa	Oklahoma
United States	Allegiance Research Specialists	Wauwatosa	Wisconsin
United States	Midatlantic Cardiovascular	Westminster	Maryland
United States	Research Inst of Kansas Inc	Wichita	Kansas
United States	Buffalo Cardiology and Pulmonary Associates	Williamsville	New York
United States	Rhode Island Cardiovascular Group	Woonsocket	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
AtheroGenics

Countries where clinical trial is conducted

United States,  Canada,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Time to first incidence of any of the following: cardiovascular mortality, resuscitated cardiac arrest, non-fatal MI, and non-fatal stroke