Effectiveness of Intensive Lipid Modification Medication in Preventing the Progression of Peripheral Arterial Disease (The ELIMIT Study)
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      PAD occurring in the legs is a serious disease that affects about 8 million people in the
      United States. A person's risk for PAD increases with age but can also be raised by smoking
      or having diabetes, high blood pressure, high cholesterol, or heart disease. Symptoms of PAD
      may include leg cramps or pain while walking, foot pain while resting, and skin wounds or
      ulcers on feet and toes. However, because only about one in three people with PAD knows to
      seek treatment for these symptoms, many end up with advanced disease that requires
      significant medical intervention, such as an endovascular or other surgical procedure to open
      the blocked arteries. While these procedures are helpful in treating people with severe PAD,
      lifestyle modifications and certain medications are also needed for long-term management of
      PAD and improved quality of life. An intensive combination of lipid modifying medications may
      be superior to standard lipid modifying medications in reducing PAD-associated risk factors
      and improving overall health in people with PAD. This study will compare the effectiveness of
      an intensive combination of lipid modifying medications versus standard lipid modifying
      medications in preventing blockages and re-narrowing of arteries in people with significant
      PAD who have had an endovascular intervention.

      Participation in this study will last a minimum of 2 years and a maximum of 5 years. All
      participants will first undergo baseline assessments that will include a medical history,
      vascular and physical exam, electrocardiograph (EKG), magnetic resonance imaging (MRI) scan,
      3D ultrasound, blood pressure measurement test in the legs, treadmill walking distance test,
      urine test, blood draw, and questionnaires. A portion of the blood draw will be used for DNA
      analysis and genetic testing.

      Participants who have not had an endovascular intervention in the 3 months before study entry
      will undergo a standard of care percutaneous transluminal angioplasty (PTA) procedure. First
      these, participants will complete a series of clinical review assessments that will include a
      review of social, vascular, and clinical history. Next, they will undergo the PTA procedure,
      which will involve the inflation and deflation of a small balloon in the area of 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.

      All participants will then be assigned randomly to receive standard care plus an intensive
      combination of lipid modifying medications (Simvastatin, Plavix, aspirin, Ezetimibe, and
      Niaspan) or standard lipid modifying medications with placebo (Simvastatin, Plavix, aspirin,
      placebo Ezetimibe, and placebo Niaspan). Participants will take their assigned medications
      daily for 24 months. Follow-up visits will occur at Day 10; Week 6; and Months, 6, 12, and 24
      after beginning the study medications. During follow-up visits, participants will repeat the
      baseline assessments and the clinical review assessments from the pre-PTA visit. The Week 6
      follow-up visit will include only a blood draw, questionnaires, and the clinical review
      assessments. Participants will also be contacted by phone to check their status every 2 to 3
      months during treatment and every 6 months after treatment for up to 3 years.
    

Intervention name(s): Ezetimibe; Niaspan; Statin therapy; Standard care; Aspirin; Clopidogrel; Placebo Niaspan; Placebo Ezetimibe; Percutaneous transluminal angioplasty (PTA)
Intervention type(s): Drug; Drug; Drug; Behavioral; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Daily dose of 10 mg of Ezetimibe; Daily dose of 1500 mg of Niaspan; Daily dose of 40 mg of Simvastatin (If unable to tolerate Simvastatin, participants will take a daily dose of Atorvastatin.); Standard of medical care for PAD; Daily dose of 325 mg of aspirin; Daily dose of 75 mg of clopidogrel for 3 months or as recommended by the primary care physician; Daily dose of 1500 mg of placebo Niaspan; Daily dose of 10 mg of placebo Ezetimibe; 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.
Other intervention name(s): Zetia; Extended release niacin; Zocor; Liptior; Plavix; Endovascular intervention
Intervention MeSH terms: Aspirin; Niacin; Nicotinic Acids; Clopidogrel; Ezetimibe
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Health Services Research
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