A Trial of Alirocumab and Plaque Regression in Peripheral Arterial Disease
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|ClinicalTrials.gov Identifier: NCT02959047|
Recruitment Status : Recruiting
First Posted : November 8, 2016
Last Update Posted : October 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Peripheral Arterial Disease||Drug: Alirocumab Drug: Matching placebo||Phase 4|
PAD is characterized by lower limb arterial obstruction due to atherosclerosis. There are over 8.5 million people with PAD in the U.S. Recent data in a general population over 40 demonstrated an incidence of PAD defined by ankle brachial index (ABI) of 4.3%. Another study of over 3000 patients, mean age 59, demonstrated a prevalence of 3.9%. The prevalence is age-dependent, rising to 14.5% in those over 70. In populations at risk including diabetics or smokers, the incidence is nearly 30%. Standard cardiovascular (CV) risk factors are also risks for PAD, especially smoking, diabetes, hypertension, African-American race and chronic kidney disease. The annual rate of CV events including myocardial infarction, stroke, and CV death is 5-7%. The adjusted risk of dying of a CV event is 2-fold higher than those without PAD.
Magnetic resonance imaging (MRI) methods can accurately quantify atherosclerotic plaque in the superficial femoral artery (SFA) in patients with PAD. These measures can be performed rapidly and reproducibly with an intraclass correlation of 0.997 for intraobserver reproducibility, 0.987 for intraobserver, and 0.996 for test-retest reproducibility, Plaque regression with statins have been shown using these techniques in PAD.
Alirocumab is a PCSK9 inhibitor that effectively reduces LDL cholesterol up to 70% in patients on statins or intolerant to statins. This injectable agent has proven safe and well-tolerated, but has not yet been studied specifically in patients with peripheral arterial disease.The study will be a double blind, placebo-controlled, randomized study of Alirocumab vs. placebo in 54 patients with PAD.
Baseline visit: Informed consent will be signed. Vital signs will be taken and blood drawn fasting for baseline values. A MRI would be performed with black blood imaging of the SFA of both legs. Approximately 10-15 cm of each leg would be covered, using a specifically designed surface coil (Machnet, Leiden, NL). The imaging would start at the bifurcation of the common femoral and proceed distally. The pulse sequence used will be a black blood turbo spin echo proton density weighted sequence with 3mm slice thickness and 3mm gaps that will be subsequently interleaved. A single slice with an extensive amount of plaque will be chosen for imaging of plaque characteristics including T1- and T2-W imaging. Finally, a calf muscle perfusion study will be performed in the leg that is most symptomatic and/or has the lowest ABI in the absence of claudication symptoms. The calf will be wrapped in a flexible surface coil in a 3T scanner. Subjects will be placed supine in the MR scanner with the calf at the magnet isocenter. A thigh cuff will be inflated up to 250 mmHg for 5 min. Arterial spin labeling images of the mid-calf will be obtained immediately after release of the cuff.Regions of interest will be drawn on the relative blood flow maps corresponding to calf muscle groups to measure perfusion in ml/min/100g.
Randomization: The study statistician will do a block randomization and let the pharmacy know. Patients in the treatment group will begin treatment with alirocumab or matching placebo, 150 mg subcutaneously every 2 weeks. Treatment will continue for 26 treatments or 1 year.
Final Visit: This will be a repeat of the initial visit with vital signs, blood draw for lipid panel, and repeat MRI with the exact same protocol as on the initial visit.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Double Blind, Randomized Trial of Alirocumab and Plaque Regression in Peripheral Arterial Disease|
|Actual Study Start Date :||July 17, 2017|
|Estimated Primary Completion Date :||July 17, 2020|
|Estimated Study Completion Date :||July 17, 2021|
Alirocumab 150mg SQ every 2 weeks
150mg SQ every 2 weeks
Other Name: Praluent
Placebo Comparator: Placebo
Drug: Matching placebo
SQ every 2 weeks
- Change in superficial femoral plaque volume (summed from both legs) [ Time Frame: 1 year ]Measured by black blood MRI, expressed in cm3
- Change in calf muscle perfusion in the most symptomatic leg [ Time Frame: 1 year ]Measured by arterial spin labeling MRI, expressed in ml/min/100g
- Change in plaque characteristics [ Time Frame: 1 year ]% lipid in one slice from each leg
- Change in 6-minute walk test [ Time Frame: 1 year ]expressed in feet
- Change in LDL cholesterol [ Time Frame: 1 year ]
- Change in high sensitivity c-reactive protein [ Time Frame: 1 year ]
- Change in fibrinogen [ Time Frame: 1 year ]
- Change in lipoprotein (a) [ Time Frame: 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02959047
|Contact: Christopher M Kramer, MDfirstname.lastname@example.org|
|Contact: Jennifer R Kay, BSNemail@example.com|
|United States, Illinois|
|Northwestern University||Not yet recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Mary McDermott, MD 312-503-6419 firstname.lastname@example.org|
|United States, Virginia|
|University of Virginia Health System||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Christopher M Kramer 434-243-0736 email@example.com|
|Principal Investigator:||Christopher M Kramer, MD||University of Virginia Health System|