Niacin Plus Statin to Prevent Vascular Events

NCT00120289 | Terminated Phase 3 Results DMC

• 3 other identifiers: 226U01HL081649U01HL081616
• Study Type: interventional
• Target: 3,414
• Locations: 2 countries
• Sites: 91

Brief Summary

The purpose of this study is to determine whether raising "good cholesterol" with a drug based on the vitamin niacin, while lowering "bad cholesterol" with a statin drug, can prevent more heart disease than the statin alone.

Conditions

Cardiovascular Diseases; Heart Diseases; Cerebrovascular Accident; Coronary Disease; Atherosclerosis; Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• Composite End Point of CHD Death, Nonfatal MI, Ischemic Stroke, Hospitalization for Non-ST Segment Elevation Acute Coronary Syndrome (ACS), or Symptom-driven Coronary or Cerebral Revascularization

  Time to first event measured from date of randomization through last follow-up visit (common termination) for an average of 36 months follow-up, maximum 66 months.

Secondary Outcomes (3)

• Composite Endpoint of CHD Death, Non-fatal MI, High-risk ACS or Ischemic Stroke

  Time to first event measured from date of randomization through last follow-up visit (common termination) for an average of 36 months follow-up, maximum 66 months

• Composite Endpoint of CHD Death, Non-fatal MI, or Ischemic Stroke

  Time to first event measured from date of randomization through last follow-up visit (common termination) for an average of 36 months follow-up, maximum 66 months

• Cardiovascular Mortality

  Time to first event measured from date of randomization through last follow-up visit (common termination), for an average of 36 months follow-up, maximum 66 months.

Study Arms (2)

Combination Therapy

EXPERIMENTAL

Extended release niacin plus simvastatin

Drug: Extended release niacin; Drug: Simvastatin

Monotherapy

ACTIVE COMPARATOR

Simvastatin alone

Drug: Simvastatin

Interventions

Extended release niacin DRUG

2,000 mg/day or 1,500 mg/day if higher dose not tolerated

Also known as: Niaspan

Combination Therapy

Simvastatin DRUG

Dose adjusted to achieve LDL-C 40 mg/dL - 80 mg/dL, adding ezetimibe (10 mg/day) if needed to achieve LDL-C target

Also known as: Zocor

Combination Therapy; Monotherapy

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 45 and older with established vascular disease and atherogenic dyslipidemia
• Established vascular disease defined as one or more of the following: (1) documented coronary artery disease (CAD); (2) documented cerebrovascular or carotid disease; (3) documented symptomatic peripheral arterial disease (PAD)
• Atherogenic dyslipidemia defined as: (1) LDL-C of less than or equal to 160 mg/dL (4.1 mmol/L); (2) HDL-C of less than or equal to 40 mg/dL (1.0 mmol/L) for men or less than or equal to 50 mg/dL (1.3 mmol/L) for women; (3) TG greater than or equal to 150 mg/dL (1.7 mmol/L) and less than or equal to 400 mg/dL (4.5 mmol/L)
• For patients entering the trial on a statin: (1) the upper limit for LDL-C is adjusted according to the specific statin and statin dose; (2) HDL-C of less than or equal to 42 mg/dL (1.1 mmol/L) for men or less than or equal to 53 mg/dL (1.4 mmol/L) for women; (3) TG greater than or equal to 125 mg/dL (1.4 mmol/L) and less than or equal to 400 mg/DL (4.5 mmol/L)

You may not qualify if:

• Coronary artery bypass graft (CABG) surgery within 1 year of planned enrollment (run-in phase)
• Percutaneous coronary intervention (PCI) within 4 weeks of planned enrollment (run-in phase)
• Hospitalization for acute coronary syndrome and discharge within 4 weeks of planned enrollment (run-in phase)
• Fasting glucose greater than 180 mg/dL (10 mmol/L) or hemoglobin A1C greater than 9%
• For patients with diabetes, inability or refusal to use a glucometer for home monitoring of blood glucose
• Concomitant use of drugs with a high probability of increasing the risk for hepatotoxicity or myopathy, such as those predominantly metabolized by cytochrome P450 system 3A4, including but not limited to cyclosporine, gemfibrozil, fenofibrate, itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, verapamil, amiodarone; lipid-lowering drugs (other than the investigational drugs) such as statins, bile-acid sequestrants, cholesterol absorption inhibitors (e.g., ezetimibe), fibrates or high-dose, antioxidant vitamins (vitamins C, E, or beta carotene) that can interfere with the HDL-raising effect of niacin

Sponsors & Collaborators

• Axio Research. LLC: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Abbott: collaborator

Study Sites (91)

Cardiovascular Associates, P.C.

Birmingham, Alabama, 35213, United States

Location

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

Clinical Research Consultants, Inc.

Hoover, Alabama, 35216, United States

Location

Carl T. Hayden VAMC Phoenix Medical Service

Pheonix, Arizona, 85012, United States

Location

Cardiovascular Consultants Ltd

Phoenix, Arizona, 85015, United States

Location

Diabetes Center of Excellence

Phoenix, Arizona, 85016, United States

Location

Tucson Clinical Research (Eastside Site)

Tucson, Arizona, 85712, United States

Location

Tucson Clinical Research (Northwest Site)

Tucson, Arizona, 85741, United States

Location

University of Arkansas

Little Rock, Arkansas, 72205, United States

Location

Providence Saint Joseph Medical Center

Burbank, California, 91505, United States

Location

VA Long Beach Healthcare System

Long Beach, California, 90822, United States

Location

Providence Holy Cross Medical Center

Mission Hills, California, 91345, United States

Location

Christiana Care Health Services

Newark, Delaware, 19718, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Heart & Vascular Research Center

Sarasota, Florida, 34239, United States

Location

James A. Haley Veteran's Hospital

Tampa, Florida, 33612, United States

Location

Idaho State University

Pocatello, Idaho, 83201, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46805, United States

Location

Iowa Heart Center, P.C.

Des Moines, Iowa, 50314, United States

Location

Lipid Research Clinic, University of Iowa

Iowa City, Iowa, 52240, United States

Location

Maine Center for Lipids & Cardiovascular Health

Scarborough, Maine, 04074, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Pentucket Medical Associates

Haverhill, Massachusetts, 01830, United States

Location

Veterans Affairs Health System of Ann Arbor, Michigan

Ann Arbor, Michigan, 48105, United States

Location

Grunberger Diabetes Institute

Bloomfield Hills, Michigan, 48302, United States

Location

Berman Center for Outcomes and Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

HealthPartners Riverside Clinic

Minneapolis, Minnesota, 55454, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Phalen Village Clinic

Saint Paul, Minnesota, 55106, United States

Location

University of Minnesota

Twin Cities, Minnesota, 55414, United States

Location

G.V. (Sonny) Montgomery VAMC

Jackson, Mississippi, 39216, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Alegent Health Heart & Vascular Specialists

Papillion, Nebraska, 68046, United States

Location

Cooper Clinical Trials Center

Cherry Hill, New Jersey, 08034, United States

Location

Cardiovascular Associates of the Delaware Valley

Elmer, New Jersey, 08318, United States

Location

UMDNJ -Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

New Mexico VA Healthcare Systems

Albuquerque, New Mexico, 87108, United States

Location

Kaleida Health/Diabetes Center

Buffalo, New York, 14209, United States

Location

Mid Valley Cardiology

Kingston, New York, 12401, United States

Location

VA New York Harbor Healthcare System

New York, New York, 10010, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Syracuse Preventive Cardiology

Syracuse, New York, 13202, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University - Geriatrics/Gerontology

Greensboro, North Carolina, 27157, United States

Location

Wake Forest University Health Sciences - Department of Cardiology

Winston-Salem, North Carolina, 27157, United States

Location

Wake Forest University School of Medicine - Internal Medicine/Endocrinology

Winston-Salem, North Carolina, 27157, United States

Location

Sterling Research Group, Ltd.

Cincinnati, Ohio, 45219, United States

Location

St Vincent Charity Hospital - The Center for Vascular Health

Cleveland, Ohio, 44115, United States

Location

North Ohio Research, Ltd.

Sandusky, Ohio, 44870, United States

Location

Portland VA Medical Center

Portland, Oregon, 97239, United States

Location

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Cardiology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Cardiology Consultants of Philadelphia

Philadelphia, Pennsylvania, 19148, United States

Location

Women's Cardiac Center at The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Internal Medicine Associates of Greenville

Greenville, South Carolina, 29607, United States

Location

VAMC Memphis - Hypertension/Lipid Research Clinic

Memphis, Tennessee, 38104, United States

Location

Kelsey Research Foundation

Houston, Texas, 77005, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Methodist Hospital

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

University of Virginia - UVA Cardiology

Charlottesville, Virginia, 22908, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

University of Washington, Northwest Lipid Research Center

Seattle, Washington, 98104, United States

Location

University of Washington, Coronary Atherosclerosis Research Lab

Seattle, Washington, 98105, United States

Location

VA Cardiology Research

Seattle, Washington, 98108, United States

Location

Washington State University

Spokane, Washington, 99202, United States

Location

CARE Foundation, Inc.

Wausau, Wisconsin, 54401, United States

Location

Heart Health Institute

Calgary, Alberta, T2E 7C5, Canada

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Vancouver Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Victoria Heart Institute

Victoria, British Columbia, V8R 4R2, Canada

Location

Health Sciences Center, Diabetes Research Group

Winnipeg, Manitoba, R3E 3R4, Canada

Location

New Brunswick Heart Center

Saint John, New Brunswick, E2L 4L2, Canada

Location

Memorial University of Newfoundland

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H 3A6, Canada

Location

Cardiology Associates VRH

Kentville, Nova Scotia, B4N 5E3, Canada

Location

Cambridge Cardiac Care Center

Cambridge, Ontario, N1R 6V6, Canada

Location

McConnell Medical Center

Cornwall, Ontario, K6H 4M4, Canada

Location

Sudbury Cardiovascular Research

Greater Sudbury, Ontario, P3E 2N8, Canada

Location

Hamilton Health Sciences - General Site

Hamilton, Ontario, L8L 2X2, Canada

Location

LHSC University Hospital

London, Ontario, N6A 5A5, Canada

Location

Newmarket Cardiology Research Group

Newmarket, Ontario, L3Y 8C3, Canada

Location

St. Michael's Hospital Health Centre

Toronto, Ontario, M5C 2T2, Canada

Location

Clinique de Cardiologie de Lévis

Lévis, Quebec, G6V 4Z5, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Recherches Clinicar

Québec, Quebec, G1J 1Z6, Canada

Location

Clinique des maladies lipidiques de Québec

Québec, Quebec, G1V 4M6, Canada

Location

CSSS Beauce

St-Georges de Beauce, Quebec, G5Y 4T8, Canada

Location

CSSS du Sud de Lanaudière - Hôpital Pierre-Le Gardeur

Terrebonne, Quebec, J6V 2H2, Canada

Location

Related Publications (10)

• AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: impact on Global Health outcomes (AIM-HIGH) trial. Am Heart J. 2011 Mar;161(3):538-43. doi: 10.1016/j.ahj.2010.12.007. Epub 2011 Feb 2.

  PMID: 21392609 BACKGROUND

• AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J. 2011 Mar;161(3):471-477.e2. doi: 10.1016/j.ahj.2010.11.017. Epub 2011 Feb 2.

  PMID: 21392600 BACKGROUND

• AIM-HIGH Investigators; Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011 Dec 15;365(24):2255-67. doi: 10.1056/NEJMoa1107579. Epub 2011 Nov 15.

  PMID: 22085343 RESULT

• Teo KK, Goldstein LB, Chaitman BR, Grant S, Weintraub WS, Anderson DC, Sila CA, Cruz-Flores S, Padley RJ, Kostuk WJ, Boden WE; AIM-HIGH Investigators. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial. Stroke. 2013 Oct;44(10):2688-93. doi: 10.1161/STROKEAHA.113.001529. Epub 2013 Jul 23.

  PMID: 23881958 RESULT

• Albers JJ, Slee A, O'Brien KD, Robinson JG, Kashyap ML, Kwiterovich PO Jr, Xu P, Marcovina SM. Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013 Oct 22;62(17):1575-9. doi: 10.1016/j.jacc.2013.06.051. Epub 2013 Aug 21.

  PMID: 23973688 RESULT

• Guyton JR, Slee AE, Anderson T, Fleg JL, Goldberg RB, Kashyap ML, Marcovina SM, Nash SD, O'Brien KD, Weintraub WS, Xu P, Zhao XQ, Boden WE. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013 Oct 22;62(17):1580-4. doi: 10.1016/j.jacc.2013.07.023. Epub 2013 Jul 31.

  PMID: 23916935 RESULT

• Ronsein GE, Vaisar T, Davidson WS, Bornfeldt KE, Probstfield JL, O'Brien KD, Zhao XQ, Heinecke JW. Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects. Arterioscler Thromb Vasc Biol. 2021 Aug;41(8):2330-2341. doi: 10.1161/ATVBAHA.121.316278. Epub 2021 Jun 17.

  PMID: 34134520 DERIVED

• Tuteja S, Qu L, Vujkovic M, Dunbar RL, Chen J, DerOhannessian S, Rader DJ. Genetic Variants Associated With Plasma Lipids Are Associated With the Lipid Response to Niacin. J Am Heart Assoc. 2018 Oct 2;7(19):e03488. doi: 10.1161/JAHA.117.008461.

  PMID: 30371334 DERIVED

• Toth PP, Jones SR, Slee A, Fleg J, Marcovina SM, Lacy M, McBride R, Boden WE. Relationship between lipoprotein subfraction cholesterol and residual risk for cardiovascular outcomes: A post hoc analysis of the AIM-HIGH trial. J Clin Lipidol. 2018 May-Jun;12(3):741-747.e11. doi: 10.1016/j.jacl.2018.03.077. Epub 2018 Mar 9.

  PMID: 29627296 DERIVED

• O'Brien KD, Hippe DS, Chen H, Neradilek MB, Probstfield JL, Peck S, Isquith DA, Canton G, Yuan C, Polissar NL, Zhao XQ, Kerwin WS. Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging. Atherosclerosis. 2016 Feb;245:74-81. doi: 10.1016/j.atherosclerosis.2015.11.032. Epub 2015 Dec 1.

  PMID: 26708287 DERIVED

Related Links

• AIM-HIGH Web site for patients

MeSH Terms

Conditions

Cardiovascular Diseases; Heart Diseases; Stroke; Coronary Disease; Atherosclerosis; Myocardial Infarction

Interventions

Niacin; Simvastatin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Ruth McBride
• Organization: Axio Research, LLC

ruthm@axioresearch.com

206-577-0212

Study Officials

• Ruth McBride

  Axio Research Corporation

  STUDY DIRECTOR

• William E. Boden, MD

  Samuel S. Stratton VA Medical Center

  PRINCIPAL INVESTIGATOR

• Jeffrey Probstfield, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Director, Coordinating Center

Study Record Dates

• First Submitted: July 6, 2005
• First Posted: July 15, 2005
• Study Start: September 1, 2005
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 6, 2016
• Results First Posted: June 17, 2015

Record last verified: 2016-03

Locations

US (68); CA (23)