Clinical trial NCT00132743 (phase 3, status: unknown status)
Conditions: cardiovascular diseases, peripheral vascular diseases, atherosclerosis
ICD codes: A52.00, A52.09, A50.54, Z01.810, Q87.418, Z13.6, R94.30, I73.9, I73.89, I67.2, I70.90, I70.91, I70.0, I70.1, I70.8, I25.83
Drugs: cilostazol
SMILES: O=C1CCC2=C(N1)C=CC(OCCCCC1=NN=NN1C1CCCCC1)=C2
Eligibility criteria:

        Inclusion Criteria:

          -  Subject has symptoms suggestive of intermittent claudication, such as exercise-induced
             pain, cramps, fatigue, or other equivalent discomfort, involving large muscle groups
             of the leg(s) (calf, thigh, buttocks), relieved by rest

          -  Claudication score consistent with "Rose", "atypical", or "noncalf" claudication by
             San Diego Claudication Questionnaire

          -  Positive noninvasive evaluation for significant aortoiliac PAD on the most symptomatic
             side(s) (bilaterally if symptoms are equal):

               -  Contrast Arteriography: Contrast arteriogram showing at least 50% stenosis in the
                  aorta, common iliac artery, or external iliac artery, OR

               -  CTA or MRA: Ankle-brachial index less than or equal to 0.9 (or abnormal ankle PVR
                  waveform at ankle if arteries are incompressible*) with at least 60% stenosis in
                  the aorta, common iliac artery, external iliac artery, accompanied by a biphasic
                  or monophasic Doppler wave form at the common femoral artery (loss of early
                  diastolic flow reversal or loss of forward flow during diastole), OR

               -  Duplex Ultrasound: Ankle-brachial index less than or equal to 0.9 (or abnormal
                  ankle PVR waveform at ankle if arteries are incompressible*) with occlusion or
                  focal doubling of peak systolic velocity in the aorta, common iliac artery, or
                  external iliac artery, accompanied by a biphasic or monophasic Doppler wave form
                  at the common femoral artery (loss of early diastolic flow reversal or loss of
                  forward flow during diastole), OR

               -  Vascular Noninvasive Physiologic Tests: Ankle-brachial index less than or equal
                  to 0.9 (or abnormal ankle PVR waveform at ankle if arteries are incompressible*)
                  with resting thigh-brachial index (thigh-BI) less than 1.1, and common femoral
                  artery Doppler systolic acceleration time greater than 140 msec [these tests may
                  be ordered for study screening].

                    -  Abnormal PVR waveform must lack augmentation at the ankle, have a delayed,
                       rounded systolic peak, and straight or convex downslope, and must be
                       reviewed by the core lab.

        Note: MRA/CTA, and contrast arteriogram images images must be submitted to the Clinical
        Coordinating Center and Doppler waveform tracings to the Noninvasive Test Committee for
        over read pre- or post-randomization

          -  Highest ankle pressure reduced by at least 25 mm Hg after exercise compared to resting
             pressure (or loss of previously present Doppler signal for both the posterior tibial
             and anterior tibial arteries immediately after exercise if arteries were
             incompressible) Note: The highest ankle pressure result is determined by using the
             higher result of either the dorsalis pedis or posterior tibial artery measurement.

          -  Subject has moderate to severe claudication symptoms, defined as less than 11 minutes
             MWD at baseline (initial) Gardner treadmill test

        Exclusion Criteria:

          -  Presence of critical limb ischemia (Rutherford Grade II or III59 PAD, defined as pain
             at rest, ischemic ulceration, gangrene) or acute limb ischemia (pain, pallor,
             pulselessness, paresthesias, paralysis) in either leg

          -  Common femoral artery (CFA) occlusion or greater than or equal to 50% stenosis by
             angiography, MRA, CTA, or duplex ultrasound or doubling of systolic velocity in the
             ipsilateral common femoral artery by duplex ultrasound, or 50% diameter stenosis by
             visual estimate in the CFA by angiography, MRA, or CTA, (inadequate outflow for iliac
             stent intervention), if available pre-randomization

          -  Known total aortoiliac occlusion from the renal arteries to the inguinal ligaments
             (all other occlusions, including aortic occlusion, ARE eligible)

          -  Participant has bilateral claudication symptoms and the limb that is more symptomatic
             does not show evidence of aortoiliac insufficiency as described in inclusion criterion
             number 5

          -  Participant has bilateral claudication symptoms, but both limbs are equally
             symptomatic and one side does not show evidence of aortoiliac insufficiency as
             described in inclusion criterion number 5

          -  Subject meets the following exclusions based upon modified American College of Sports
             Medicine criteria for exercise training:

             i. Ambulation limited by co-morbid condition other than claudication, for example:1.
             severe coronary artery disease; 2. angina pectoris; 3. chronic lung disease;4.
             neurological disorder such as hemiparesis;5. arthritis, or other musculoskeletal
             conditions including amputation ii. Poorly-controlled hypertension (SBP greater than
             180 mm Hg) iii.Poorly-controlled diabetes mellitus iv. Other active significant
             medical problems such as cancer, known chronic renal disease (serum creatinine greater
             than 2.0 mg/dl within 60 days or renal replacement therapy), known chronic liver
             disease or anemia, active substance abuse, or known history of dementia

          -  Contraindication to exercise testing according to AHA/ACC guideline, specifically:
             Acute myocardial infarction (within 3-5 days), unstable angina, uncontrolled cardiac
             arrhythmias causing symptoms or hemodynamic compromise, active endocarditis,
             symptomatic severe aortic stenosis, acute pulmonary embolus or pulmonary infarction,
             acute noncardiac disorder that may affect exercise performance or be aggravated by
             exercise such as infection, thyrotoxicosis, acute myocarditis or pericarditis, known
             physical disability that would preclude safe and adequate test performance, known
             thrombosis of the lower extremity, known left main coronary stenosis or its
             equivalent, moderate stenotic valvular heart disease, electrolyte abnormalities, known
             pulmonary hypertension, tachyarrhythmias or bradyarrhythmias, hypertrophic
             cardiomyopathy, mental impairment leading to inability to cooperate, or high degree
             atrioventricular block

          -  Arterial insufficiency of target lesion due to restenosis of an angioplasty/stent or
             bypass is not eligible

          -  Recent (less than 3 months) infrainguinal revascularization (surgery or endovascular
             intervention)

          -  Recent major surgery in the last 3 months

          -  Abdominal aortic aneurysm greater than 4 cm or iliac artery aneurysm greater than 1.5
             cm is present

          -  Patients who are pregnant, planning to become pregnant, or lactating

          -  Unwilling or unable to attend regular (3 times a week) supervised exercise sessions.
             (Please review this commitment carefully with each prospective participant.)

          -  Weight greater than 350 lbs or 159 kg (may exceed treadmill and angiography table
             limits)

          -  Inability to understand and sign informed consent forms due to cognitive or language
             barriers (interpreter permitted)

          -  Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid
             reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) and
             which would preclude patient from participation in angiographic procedures

          -  Allergy to stainless steel or nitinol

          -  Allergy or other intolerance to cilostazol (bleeding history) or history of congestive
             heart failure [if ejection fraction is shown to be greater than or equal to 50%
             patient may be enrolled]

          -  Nonatherosclerotic cause of PAD (fibromuscular dysplasia, dissection, trauma, etc)

          -  Inability to walk on a treadmill without grade at a speed of at least 2 mph for at
             least 2 minutes on the first treadmill test

          -  ST-segment depression greater than 1 mm in any of the standard 12 ECG leads or
             sustained (greater than 30 seconds) arrhythmia other than tachycardia or occasional
             premature atrial or ventricular contractions during exercise testing

          -  Post-exercise systolic blood pressure within the first five minutes after eligibility
             treadmill test lower than pre-exercise systolic blood pressure

          -  A peak heart rate greater than 80% of maximum (calculated by subtracting age from 220)
             while reporting "onset" of claudication symptoms (level 3 or 4) during the second
             baseline examination

          -  Repeat treadmill test shows a MWD result that is greater than 25% different than the
             subject's initial Gardner treadmill test result. Current active involvement in a
             supervised exercise program (e.g., with a trainer, exercise protocol, and goals, such
             as in cardiac or pulmonary rehabilitation) for more than 2 weeks within the prior 6
             weeks.