The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial

Study Overview
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Brief Summary
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This is a phase IV, multi-center, double-blind, randomized, placebo- controlled study evaluating the effect of alirocumab on SVG atherosclerotic disease burden, as assessed by IVUS at baseline and following 78 weeks of treatment in subjects with at least one intermediate SVG lesion receiving optimal statin therapy. Subjects will be randomized 1:1 into 2 treatment groups: alirocumab 150 mg subcutaneously every 2 weeks or placebo subcutaneously every 2 weeks.

Official Title
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Effect of Alirocumab on Saphenous Vein Graft Atherosclerosis: The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial

Conditions
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Saphenous Vein Graft Atherosclerosis

Intervention / Treatment
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* Drug: Alirocumab 150 MG/ML subcutaneous injection
* Drug: Matching Placebo subcutaneous injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or greater. Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up. Undergoing clinically-indicated coronary and SVG angiography. Have at least one target saphenous vein graft with an intermediate SVG lesion (defined as a lesion with 30-60% angiographic diameter stenosis) amenable to examination with IVUS. The SVG should have no thrombus or ulceration and should not be considered responsible for the patient's clinical presentation and referral for angiography. Receiving optimal statin therapy defined as use of a high intensity statin (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily), any statin therapy with achieved LDL-C level <70mg/dL, or maximally-tolerated statin dose for patients who are statin intolerant statin. Exclusion Criteria: Positive pregnancy test or breast-feeding. Coexisting conditions that limit life expectancy to less than 18 months or that could affect a patient's compliance with the protocol. Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2. Severe peripheral arterial disease limiting vascular access. History of allergic reaction to iodine-based contrast agents that cannot be premedicated. Known hypersensitivity to alirocumab. Any prior use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alirocumab 150 MG/ML subcutaneous injection<br>Alirocumab 150 mg subcutaneously every 2 weeks | Drug: Alirocumab 150 MG/ML subcutaneous injection<br>* Single-dose, pre-filled, disposable, subcutaneous injection pen<br>* Other names: Praluent, Study Drug;|
| Placebo Comparator: Matching Placebo subcutaneous injection<br>Matching placebo subcutaneously every 2 weeks | Drug: Matching Placebo subcutaneous injection<br>* Single-dose, pre-filled, disposable, subcutaneous injection pen<br>* Other names: Placebo, Study Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nominal change in intermediate SVG lesion percent atheroma volume (PAV) from baseline to 78 weeks post randomization, as assessed by intravascular ultrasonography (IVUS). | To evaluate the effect of alirocumab on the change in burden of saphenous vein graft (SVG) atherosclerosis as measured by percent atheroma volume (PAV) in patients with intermediate SVG lesions who are undergoing clinically-indicated coronary angiography and are receiving optimal statin therapy. | 78 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nominal change in TAV and normalized TAV of an intermediate SVG lesion from baseline to 78 weeks | evaluate the effect of alirocumab on the change in total and normalized total atheroma volume (TAV) of an intermediate SVG lesion | 78 weeks | 
| Angiographic failure of target SVG lesion from baseline to 78 weeks. | To evaluate the effect of alirocumab on the incidence of angiographic failure of an intermediate target SVG lesion. | 78 weeks | 
| Incidence of target SVG failure and major adverse cardiac events. | To evaluate the effect of alirocumab on the incidence of target SVG failure (defined as the composite of death, myocardial infarction, and target lesion revascularization) and the incidence of major adverse cardiac events (MACE, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up. | Randomization to 80 weeks |