The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies. Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments. The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

The purpose of this trial is to determine the most effective treatment method to prevent strokes in people who have narrowing in the carotid artery but no stroke symptoms caused by the blockage of that artery.

Prevention of stroke involves managing and treating risk factors. Most strokes are caused when blood flow to a portion of the brain is blocked. One place this often happens is in the carotid artery. This blockage is called atherosclerosis or hardening of the arteries.

CREST-2 consists of 2 parallel, randomized clinical trials.  One trial will compare intensive medical management to carotid endarterectomy plus intensive medical management.  The parallel trial will compare intensive medical management to carotid artery stenting plus intensive medical management. Intensive medical management will involve a lifestyle intervention to monitor and manage risk factors such as blood pressure, cholesterol, smoking cessation, weight loss, and physical activity.

An estimated 2480 participants will be enrolled in CREST-2 at approximately 120 sites in the United States and Canada.  Each eligible participant will be evaluated to determine which procedure is best for him/her. All participants will receive intensive medical treatment.  Participants will remain in the study up to 4 years.

Eligibility Criteria:

General Inclusion Criteria

  1. Patients ≥35 years old.
  2. Carotid stenosis defined as:

    • Stenosis ≥70% by catheter angiography (NASCET Criteria); OR
    • by DUS with ≥70% stenosis defined by a peak systolic velocity of at least 230 cm/s plus at least one of the following:

      1. an end diastolic velocity ≥100 cm/s, or
      2. internal carotid/common carotid artery peak systolic velocity ratio ≥4.0, or
      3. CTA with ≥ 70% stenosis, or
      4. MRA with ≥ 70% stenosis.
  3. No medical history of stroke or TIA ipsilateral to the stenosis within 180 days of randomization. Life-long asymptomatic patients will be defined as having no medical history of stroke or transient ischemic attack and negative responses to all of the symptom items on the Questionnaire for Verifying Stroke-free Status (QVSS).
  4. Patients must have a modified Rankin Scale score of 0 or 1 at the time of informed consent.
  5. Women must not be of childbearing potential or, if of childbearing potential, have a negative pregnancy test prior to randomization.
  6. Patients must agree to comply with all protocol-specified follow-up appointments.
  7. Patients must sign a consent form that has been approved by the local governing Institutional Review Board (IRB)/Medical Ethics Committee (MEC) of the respective clinical site.
  8. Randomization to treatment group will apply to only one carotid artery for patients with bilateral carotid stenosis. Management of the non-randomized stenosis may be done in accordance with local PI recommendation. Treatment of the non-study internal carotid artery must take place at least 30 days prior to randomization, or greater than 44 days after randomization and 30 days after the study procedure is completed (whichever is longer).
  9. Carotid stenosis must be treatable with CEA, CAS, or either procedure

General Exclusion Criteria

  1. Intolerance or allergic reaction to a study medication without a suitable management alternative.
  2. GI hemorrhage within 1 month prior to enrollment that would preclude antiplatelet therapy.
  3. Prior major ipsilateral stroke in the past with substantial residual disability (mRS ≥ 2) that is likely to confound study outcomes.
  4. Severe dementia.
  5. Intracranial hemorrhage within the past 12 months.
  6. Current neurologic illness characterized by fleeting or fixed neurologic deficits that cannot be distinguished from TIA or stroke.
  7. Patient objects to future blood transfusions.
  8. Platelet count <100,000/μl or history of heparin-induced thrombocytopenia.
  9. Anticoagulation with Phenprocoumon (Marcumar®), warfarin, or a direct thrombin inhibitor, or anti-Xa agents.
  10. Chronic atrial fibrillation.
  11. Any episode of atrial fibrillation within the past 6 months or history of paroxysmal atrial fibrillation that is deemed to require chronic anticoagulation.
  12. Other high-risk cardiac sources of emboli, including left ventricular aneurysm, severe cardiomyopathy, aortic or mitral mechanical heart valve, severe calcific aortic stenosis (valve area < 1.0 cm2), endocarditis, moderate to severe mitral stenosis, left atrial thrombus, or any intracardiac mass, or known unrepaired PFO with prior paradoxical embolism.
  13. Unstable angina defined as rest angina with ECG changes that is not amenable to revascularization (patients should undergo planned coronary revascularization at least 30 days before randomization).
  14. Left Ventricular Ejection fraction <30% or admission for heart failure in prior 6 months.
  15. Respiratory insufficiency with life expectancy < 4 years or FEV1 <30% of predicted value.
  16. Known malignancy other than basal cell non-melanoma skin cancer. There are two exceptions to this rule: patients with prior cancer treatment and no recurrence for >5 years are eligible for enrollment and cancer patients with life expectancy of greater than 5 years are eligible for enrollment.
  17. Any major surgery, major trauma, revascularization procedure, or acute coronary syndrome within the past 1 month.
  18. Serum creatinine ≥2.5 mg/dl or estimated GFR ≤40 cc/min (at screening).
  19. Major (non-carotid) surgery/procedures planned within 3 months after enrollment.
  20. Currently listed or being evaluated for major organ transplantation (i.e. heart, lung, liver, kidney).
  21. Actively participating in another drug or aortic arch or cerebrovascular device trial for which participation in CREST-2 would be compromised with regard to follow-up assessment of outcomes or continuation in CREST-2.
  22. Inability to understand and cooperate with study procedures or provide informed consent.
  23. Non-atherosclerotic carotid stenosis (dissection, fibromuscular dysplasia, or stenosis following radiation therapy).
  24. Previous ipsilateral CEA or CAS.
  25. Ipsilateral internal or common carotid artery occlusion.
  26. Intra-carotid floating thrombus.
  27. Ipsilateral intracranial aneurysm > 5 mm.
  28. WHO Class III obesity (BMI >40 kg/m2).
  29. Contra-lateral common or internal carotid artery occlusion.
  30. Coronary artery disease with two or more proximal or major diseased coronary arteries with ≥ 70% stenosis that have not, or cannot, be revascularized.
  31. Any of the following anatomical: radical neck dissection; surgically inaccessible lesions (e.g. above cervical spine level 2 (C2)); adverse neck anatomy that limits surgical exposure (e.g. spinal immobility - inability to flex neck beyond neutral or kyphotic deformity, or short obese neck); presence of tracheostomy stoma; laryngeal nerve palsy contralateral to target vessel; or previous extracranial-intracranial or subclavian bypass procedure ipsilateral to the target vessel.
  32. Occlusive or critical ilio-femoral disease including severe tortuosity or stenosis that necessitates additional endovascular procedures to facilitate access to the aortic arch or that prevents safe and expeditious femoral access to the aortic arch. "String sign" of the ipsilateral common or internal carotid artery.
  33. Angiographic, CT, MR or ultrasound evidence of severe atherosclerosis of the aortic arch or origin of the innominate or common carotid arteries.

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Study Location:

Multiple U.S. Locations

Study website: