ARISE - Aggressive Reduction of Inflammation Stops Events

NCT ID: NCT00066898

Last Updated: 2006-10-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 6000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2006-12-31

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.

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.

Conditions

Atherosclerosis; Coronary Artery Disease; Myocardial Infarction; Unstable Angina

Keywords

succinobucol; AGI-1067; coronary artery disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

AGI-1067

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AtheroGenics

INDUSTRY

Sponsor Role: lead

Principal Investigators

Marc A Pfeffer, MD

Role: STUDY_CHAIR

Cardiovascular Division Brigham and Women's Hospital

Jean-Claude Tardif, MD

Role: STUDY_CHAIR

Montreal Heart Institute

John McMurray, MD

Role: PRINCIPAL_INVESTIGATOR

Western Infirmary

Eric Klug, MD

Role: PRINCIPAL_INVESTIGATOR

Independent Medical Practitioner - South Africa

Locations

Cardiovascular Associates

Birmingham, Alabama, United States

Univ of Alabama at Birmingham

Birmingham, Alabama, United States

The Heart Center/Oracle Research

Huntsville, Alabama, United States

Tri City Cardiology Consultants

Mesa, Arizona, United States

Tri-City Cardiology Consultants

Mesa, Arizona, United States

Hope Research Institute

Phoenix, Arizona, United States

Lovelace Scientific Resources

Phoenix, Arizona, United States

Sonoran Health Specialists

Scottsdale, Arizona, United States

Capitol Interventional Cardiology

Carmichael, California, United States

Escondido Cardiology

Escondido, California, United States

Merced Heart Associates

Merced, California, United States

Orange County Research Cntr

Orange, California, United States

ARI Clinical Trials

Redondo Beach, California, United States

Radiant Research

Santa Rosa, California, United States

Pikes Peak Cardiology

Colorado Springs, Colorado, United States

Aurora Denver Cardiololgy Associates

Denver, Colorado, United States

Heart and Vascular Clinic N CO

Fort Collins, Colorado, United States

Connecticut Clinical Research

Bridgeport, Connecticut, United States

Cardiac Specialists, PC

Trumbull, Connecticut, United States

Christiana Care Health Svcs

Newark, Delaware, United States

Clinical Research of West Florida, Inc.

Clearwater, Florida, United States

SW Florida Heart Group

Fort Myers, Florida, United States

Univ of Florida, Cardiology

Gainesville, Florida, United States

Diagnostic Cardiology

Jacksonville, Florida, United States

Jacksonville Cntr Clin Research

Jacksonville, Florida, United States

Jacksonville Heart Center

Jacksonville Beach, Florida, United States

Watson Clinic LLP

Lakeland, Florida, United States

Cardiovascular Research Center of South Florida

Miami, Florida, United States

Orlando Heart Cntr

Orlando, Florida, United States

Cardiovascular Cntr of Sarasota

Sarasota, Florida, United States

The Broward Heart Group

Tamarac, Florida, United States

Clinical Research of West Florida, Inc.

Tampa, Florida, 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

Harbin Clinic

Rome, Georgia, United States

Idaho Cardiology Associates

Boise, Idaho, United States

Heart Care Research Foundation

Blue Island, Illinois, United States

Peryam and Kroll Healthcare

Chicago, Illinois, United States

Heartcare Midwest Heart Inst

Peoria, Illinois, United States

The Heart Group

Evansville, Indiana, United States

Welborn Clinic Research Center

Evansville, Indiana, United States

Parkview Hospital

Fort Wayne, Indiana, United States

Care Group St. Vincent Hosp of IN

Indianapolis, Indiana, United States

Research Inst of Middle America

Jeffersonville, Indiana, United States

Iowa Heart Center

Des Moines, Iowa, United States

Univ of IA College of Medicine

Iowa City, Iowa, United States

Research Inst of Kansas Inc

Wichita, Kansas, United States

Cardiovascular Associates

Louisville, Kentucky, United States

Louisiana Heart Center

Chalmette, Louisiana, United States

The Office of Dr. Richard Gilmore

Lake Charles, Louisiana, United States

Heart Clinic of Louisiana

Marrero, Louisiana, United States

Cardiovascular Inst of the South

Morgan City, Louisiana, 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

Medical Research Institute

Slidell, Louisiana, United States

Cardiovascular Inst of South

Thibodaux, Louisiana, United States

Androscoggin Cardiology

Auburn, Maine, United States

Midatlantic Cardiovascular Associates

Baltimore, Maryland, United States

Midatlantic Cardiovascular

Baltimore, Maryland, United States

Midatlantic Cardiovascular

Bel Air, Maryland, United States

Patuxent Medical Group

Columbia, Maryland, United States

MD Med Research Ong Med Cntr

Oxon Hill, Maryland, United States

Midatlantic Cardiovascular

Towson, Maryland, United States

Midatlantic Cardiovascular

Westminster, Maryland, United States

Compass Medical Associates

Abington, Massachusetts, United States

Gary Brockington, MD

Boston, Massachusetts, United States

Lahey Clinic Med Cntr

Burlington, Massachusetts, United States

Pentucket Med Assoc Inc

Haverhill, Massachusetts, United States

Charles River Med Associates

Natick, Massachusetts, United States

Professional Clinical Research

Cadillac, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

The Office of Dr. Keith Pierce

Livonia, Michigan, United States

Beaumont Medical Office Bldg

Royal Oak, Michigan, United States

Michigan Heart Group

Troy, Michigan, United States

St Paul Heart Clinic

Saint Paul, Minnesota, United States

N'Touch Research

Kansas City, Missouri, 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

Nebraska Heart Institute

Lincoln, Nebraska, United States

Creighton Cardiac Center

Omaha, Nebraska, United States

Nebraska Heart Institute

Papillion, Nebraska, United States

Cardiovascular Assoc of Delaware Valley

Elmer, New Jersey, United States

Cardiovascular Associates of the Delaware Valley

Haddon Heights, New Jersey, United States

SUNY Downstate Health Science Ctr

Brooklyn, New York, United States

St Vincent's Med Cntr NY

New York, New York, United States

SUNY Upstate Medical Univ

Syracuse, New York, United States

Syracuse Preventive Cardiology

Syracuse, New York, United States

Buffalo Cardiology and Pulmonary Associates

Williamsville, New York, United States

Mid Carolina Cardiology Research Div

Charlotte, North Carolina, United States

City Cardiology Associates

Akron, Ohio, 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

North Ohio Heart Center

Sandusky, Ohio, United States

Bluestem Cardiology

Bartlesville, Oklahoma, United States

COR Clinical Research, LLC

Oklahoma City, Oklahoma, United States

Castlerock Clinical Research Consultants

Tulsa, Oklahoma, United States

The Heart Care Group

Allentown, Pennsylvania, United States

Tri-State Medical Group

Beaver, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Kandra, Fierer, Kuskin Associates

Harrisburg, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Banksville Medical

Pittsburgh, Pennsylvania, United States

Rhode Island Cardiovascular Group

Woonsocket, Rhode Island, United States

Charleston Cardiology

Charleston, South Carolina, United States

Internal Medicine of Greer

Greer, South Carolina, United States

Alpha Clinical Research

Clarksville, Tennessee, United States

Cardiovascular Research Foundation

Knoxville, Tennessee, United States

Amarillo Heart Clinical Research Institute

Amarillo, Texas, United States

Pharma Tex Research

Amarillo, Texas, United States

Austin Heart PA

Austin, Texas, United States

Southeast Texas Cardiology Associates II

Beaumont, Texas, United States

Clinical Cardiovascular Research Cntr

Dallas, Texas, United States

The Methodist Hospital

Houston, Texas, United States

Research Clinic

Nassau Bay, Texas, United States

Sioco Cardiology, PA

San Antonio, Texas, United States

Heart Center

Salt Lake City, Utah, United States

IHC Health Services

Salt Lake City, Utah, United States

DUCCS Research of S Boston

South Boston, Virginia, United States

Daniel Gottlieb MD PS

Burien, Washington, United States

U of WA NW Lipid Research Cntr

Seattle, Washington, United States

Appleton Heart Inst

Appleton, Wisconsin, United States

Wisconsin Center for Clinical Research

Elkhorn, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Allegiance Research Specialists

Wauwatosa, Wisconsin, United States

Foothills Hospital Cardiology Div

Calgary, Alberta, Canada

Royal Alexandra Hospital

Edmonton, Alberta, Canada

West Coast Cardiology Research

New Westminster, British Columbia, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

St Boniface General Hospital

Winnipeg, Manitoba, Canada

Health Sciences Centre Div of Cardiology

St. John's, Newfoundland and Labrador, Canada

Queen Elizabeth Health Sciences Centre

Halifax, Nova Scotia, Canada

Halton Heart Institute

Burlington, Ontario, Canada

The Office of Dr. Syan Gurcharan

Greater Sudbury, Ontario, Canada

St Joseph Health Care Hamilton

Hamilton, Ontario, Canada

Kingston Heart Clinic

Kingston, Ontario, Canada

London Health Sci Cntr Site

London, Ontario, Canada

Mount St. Joseph's

London, Ontario, 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

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

CMGC-GRID Complexe Hosp

Chicoutimi, Quebec, 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

Hosp Regional de Lanaudiere

Joliette, Quebec, Canada

Cite de la Sante de Laval

Laval, Quebec, Canada

Clinique de Cardiologie de Levis

Lévis, Quebec, 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

Recherches Clinicar

Québec, Quebec, Canada

Cntr Hospital Beauce Etchemin

Saint George, Quebec, Canada

Reseau Sante Richelieu Yamaska

Saint-Hyacinthe, Quebec, Canada

Hopital du Haut-Richelieu

Saint-Jean-sur-Richelieu, Quebec, Canada

Zoom International

Saint-Jérôme, Quebec, Canada

Neufort Inc.

Saint-Lambert, Quebec, Canada

London Clinical Research

Sherbrooke, Quebec, Canada

Laval Hospital Pavillion 2U

Ste-Foy, Quebec, Canada

Cntr Hospitalier Pierre Le Gardeur

Terrebonne, Quebec, Canada

Centre Hospitalier de Val d'Or

Val-d'Or, Quebec, Canada

Societe des internistes Bois Fran

Victoriaville, Quebec, Canada

Pasqua Hosp Coronary Care Unit

Regina, Saskatchewan, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Saskatoon Medical Specialists

Saskatoon, Saskatchewan, Canada

Dr. Johann Viljoen

Bloemfontein, BLM, South Africa

Fichmed 5, Rosepark Hospital

Bloemfontein, BLM, South Africa

Universitas Hospital

Bloemfontein, BLM, 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

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

Mulbarton Medical Center

Mulbarton, JHB, South Africa

Olivedale Clinic

Olivedale, JHB, South Africa

Sunninghill Hospital

Sunninghill, JHB, South Africa

Pretoria Heart Hospital

Arcadia, PTA, South Africa

Unitas Hospital

Lyttelton Centurion, PTA, South Africa

Wilgers Medical Consortium

The Willows, PTA, South Africa

King's College Hospital NHS Trust

London, England, United Kingdom

Barking, Havering & Redbridge Hospital NHS Trust

Romford, Essex, 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

South Manchester University Hospitals NHS Trust

Manchester, , United Kingdom

Argyll & Clyde NHS Trust

Paisley, , 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

Stoke-on-Trent, , United Kingdom

Mid Yorkshire Hospitals

Wakefield, , United Kingdom

Countries

United States; Canada; South Africa; United Kingdom

References

Tardif JC, McMurray JJ, Klug E, Small R, Schumi J, Choi J, Cooper J, Scott R, Lewis EF, L'Allier PL, Pfeffer MA; Aggressive Reduction of Inflammation Stops Events (ARISE) Trial Investigators. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 May 24;371(9626):1761-8. doi: 10.1016/S0140-6736(08)60763-1.

Reference Type: DERIVED

PMID: 18502300 (View on PubMed)

Other Identifiers

AGI-1067/042

Identifier Type: -

Identifier Source: org_study_id