Effectiveness of Intensive Lipid Modification Medication in Preventing the Progression of Peripheral Arterial Disease (The ELIMIT Study)

NCT00687076 | Completed Phase 4 Results DMC

• 2 other identifiers: 1400R01HL075824
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral arterial disease (PAD) occurs when arteries become narrowed or hardened because of a build-up of plaque or fat deposits. PAD develops most often in arteries in the legs, which can result in reduced blood flow to the legs and feet, occasionally causing leg pain and fatigue. Early identification of PAD and treatment with lifestyle changes or medications can help to keep legs healthy and lower risk for heart attack and stroke, but endovascular or surgical procedures may be necessary for people with severe PAD. Even after endovascular intervention, PAD symptoms must be continually monitored to prevent the development and progression of blockages in the arteries. The best approach for monitoring symptoms is still undetermined. This study will compare the effectiveness of an intensive combination of lipid modifying medications versus standard lipid modifying medications in treating people with significant PAD who have had an endovascular intervention.

Conditions

Peripheral Arterial Disease

Keywords

Endovascular Intervention; MRI; Ultrasound; Cholesterol Medications; High Cholesterol; Peripheral Arterial disease; Claudication; Leg Pain; Niaspan; Extended Release Niacin; Zetia; Ezetimibe; Simvastatin; Zocor; Atorvastatin; Lipitor

Outcome Measures

Primary Outcomes (1)

• Effect of Intensive Lipid Modification Medication Therapy on Progression of Atherosclerosis and Restenosis of Femoral Arteries Measured Using High Resolution Magnetic Resonance Imaging (MRI) to Examine the Femoral Artery for Progression of Atherosclerosis

  The primary outcome variable was the change in superficial femoral artery (SFA) wall volume over 24-months, as determined by MRI. The 24-month changes in SFA lumen and SFA total vessel volumes were also analyzed. Analysis details: A total of 102 patients were randomized. 87 patients completed baseline MRI. Between randomization and the baseline visit, 1 patient withdrew from the study, 8 patients opted out from baseline imaging, and 6 additional patients declined blood collection at baseline. The multilevel models (primary endpoint) used all available imaging data (n=91), including patients who only completed baseline imaging (n=20) or completed at least 2 imaging visits other than baseline (n=4).

  Measured at baseline and 24 Months

Secondary Outcomes (1)

• Change in Total Cholesterol (mg/dl) From Baseline to Month 12

  Measured at baseline and 12 months

Study Arms (2)

1

EXPERIMENTAL

Participants will receive standard of medical care and treatment with intensive lipid modification using a statin plus Ezetimibe and Niaspan.

Drug: Ezetimibe; Drug: Niaspan; Drug: Statin therapy; Behavioral: Standard care; Drug: Aspirin; Drug: Clopidogrel; Procedure: Percutaneous transluminal angioplasty (PTA)

2

ACTIVE COMPARATOR

Participants will receive standard of medical care and treatment with standard lipid modifying medications plus placebo Ezetimibe and placebo Niaspan.

Drug: Statin therapy; Behavioral: Standard care; Drug: Aspirin; Drug: Clopidogrel; Drug: Placebo Niaspan; Drug: Placebo Ezetimibe; Procedure: Percutaneous transluminal angioplasty (PTA)

Interventions

Ezetimibe DRUG

Daily dose of 10 mg of Ezetimibe

Also known as: Zetia

1

Niaspan DRUG

Daily dose of 1500 mg of Niaspan

Also known as: Extended release niacin

1

Statin therapy DRUG

Daily dose of 40 mg of Simvastatin (If unable to tolerate Simvastatin, participants will take a daily dose of Atorvastatin.)

Also known as: Zocor, Liptior

1; 2

Standard care BEHAVIORAL

Standard of medical care for PAD

1; 2

Aspirin DRUG

Daily dose of 325 mg of aspirin

1; 2

Clopidogrel DRUG

Daily dose of 75 mg of clopidogrel for 3 months or as recommended by the primary care physician

Also known as: Plavix

1; 2

Placebo Niaspan DRUG

Daily dose of 1500 mg of placebo Niaspan

2

Placebo Ezetimibe DRUG

Daily dose of 10 mg of placebo Ezetimibe

2

Percutaneous transluminal angioplasty (PTA) PROCEDURE

Participants who have not had an endovascular intervention in the 3 months before study entry will undergo PTA to mechanically open the artery blockages. This procedure will involve the inflation and deflation of a small balloon to open the blocked artery. Additionally, participants may have a metal mesh tube called a stent placed in the blocked area if deemed necessary by their physicians.

Also known as: Endovascular intervention

1; 2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptoms consistent with calf claudication and described as life style limiting
• Objective evidence of peripheral artery disease (PAD): Ankle brachial index less than 0.9 OR other hemodynamic or imaging modalities confirming significant PAD
• Baseline imaging reveals superficial femoral artery (SFA) disease starting at least 5 cm from the origin of the SFA
• Agrees to be available for follow-up and is able to participate in all study testing procedures
• Weight and/or body characteristics that will allow testing with MRI
• No known contraindication to lipid lowering agents
• Serum creatinine level less than 2.5 mg/dL
• Scheduled to undergo or has already undergone an endovascular intervention of a de novo lesion in the SFA with an anticipated result that would satisfy hemodynamic stability OR is medically managed and does not require an intervention at this time
• Compressible arteries (if not, has toe brachial index \[TBI\] less than 0.7)
• Has/had an A, B, C lesion amendable to a catheter based therapy (prior bypass is acceptable)

You may not qualify if:

• Non-atherosclerotic disease that is responsible for claudication
• Unstable cardiac disease (e.g., unstable angina, heart attack within the 30 days before study entry, uncontrolled coronary heart failure, poorly controlled hypertension \[systolic blood pressure greater than 180 mmHg and/or diastolic blood pressure greater than 100 mmHg\], ventricular arrhythmias)
• Pancreatitis
• Documented hypercoagulable state
• Clinically severe diabetic neuropathy
• Rest pain, gangrene, or tissue loss
• Active peptic ulcer disease or a recent gastrointestinal bleed that would prohibit the use of an anti-platelet (aspirin/Plavix)
• Untreated or unsuccessfully controlled psychiatric disease
• Chronic hepatic disease determined by aspartate transaminase (AST) and/or alanine transaminase (ALT) more than 3 times upper limit of normal (ULN) and/or total bilirubin more than 2 times ULN
• Creatine phosphokinase (CPK) more than 3 times ULN (may be repeated once before patient is excluded)
• Active gout symptoms or a uric acid level greater than 1.3 times ULN
• Untreated hypothyroidism
• Allergy to Plavix, nickel, titanium, niacin, Ezetimibe, statins, or their derivatives
• Participated in another interventional study within the 30 days before study entry
• Scheduled to undergo planned synchronous bilateral percutaneous transluminal angioplasty (PTA) procedures

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Lumsden AB, Rice TW, Chen C, Zhou W, Lin PH, Bray P, Morrisett J, Nambi V, Ballantyne C. Peripheral arterial occlusive disease: magnetic resonance imaging and the role of aggressive medical management. World J Surg. 2007 Apr;31(4):695-704. doi: 10.1007/s00268-006-0732-y.

  PMID: 17345122 BACKGROUND

• Brunner G, Yang EY, Kumar A, Sun W, Virani SS, Negi SI, Murray T, Lin PH, Hoogeveen RC, Chen C, Dong JF, Kougias P, Taylor A, Lumsden AB, Nambi V, Ballantyne CM, Morrisett JD. The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Atherosclerosis. 2013 Dec;231(2):371-7. doi: 10.1016/j.atherosclerosis.2013.09.034. Epub 2013 Oct 16.

  PMID: 24267254 RESULT

• Saunders J, Nambi V, Kimball KT, Virani SS, Morrisett JD, Lumsden AB, Ballantyne CM, Dong JF; ELIMIT Investigators. Variability and persistence of aspirin response in lower extremity peripheral arterial disease patients. J Vasc Surg. 2011 Mar;53(3):668-75. doi: 10.1016/j.jvs.2010.08.029. Epub 2011 Jan 12.

  PMID: 21227624 RESULT

Related Links

• Click here for more information on peripheral arterial disease

MeSH Terms

Conditions

Peripheral Arterial Disease; Hypercholesterolemia; Intermittent Claudication

Interventions

Ezetimibe; Niacin; Simvastatin; Standard of Care; Aspirin; Clopidogrel; Angioplasty

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Catheterization; Therapeutics; Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Investigative Techniques

Limitations and Caveats

MRI was performed in the distal SFA. Ethnicity which was not part of the randomization protocol differed significantly between mono- and triple-therapy groups. The attrition rate was high in ELIMIT. ELIMIT was not powered to assess clinical outcomes.

Results Point of Contact

• Title: Gerd Brunner, PhD
• Organization: Baylor College of Medicine

gbrunner@bcm.edu

713-790-5800

Study Officials

• Christie M. Ballantyne, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: May 30, 2008
• Study Start: April 1, 2004
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: February 6, 2020
• Results First Posted: August 25, 2014

Record last verified: 2020-01

Locations

US (1)