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

Primary Purpose

Saphenous Vein Graft Atherosclerosis

Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Alirocumab 150 MG/ML subcutaneous injection
Matching Placebo subcutaneous injection
Sponsored by
Minneapolis Heart Institute Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Saphenous Vein Graft Atherosclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 18 years or greater.
  2. Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
  3. Undergoing clinically-indicated coronary and SVG angiography.
  4. 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.
  5. 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:

  1. Positive pregnancy test or breast-feeding.
  2. Coexisting conditions that limit life expectancy to less than 18 months or that could affect a patient's compliance with the protocol.
  3. Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2.
  4. Severe peripheral arterial disease limiting vascular access.
  5. History of allergic reaction to iodine-based contrast agents that cannot be premedicated.
  6. Known hypersensitivity to alirocumab.
  7. Any prior use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.

Sites / Locations

  • San Francisco VA Medical Center
  • Atlanta VA Medical Center
  • Minneapolis Heart Institute/ Abbott North Western Hospital-Allina Health
  • Dallas VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Alirocumab 150 MG/ML subcutaneous injection

Matching Placebo subcutaneous injection

Arm Description

Alirocumab 150 mg subcutaneously every 2 weeks

Matching placebo subcutaneously every 2 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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.

Full Information

First Posted
May 18, 2018
Last Updated
September 15, 2021
Sponsor
Minneapolis Heart Institute Foundation
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03542110
Brief Title
The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial
Acronym
ASAP-SVG
Official Title
Effect of Alirocumab on Saphenous Vein Graft Atherosclerosis: The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
Withdrawal of medication and funding support by Sponsor
Study Start Date
August 4, 2018 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
July 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Minneapolis Heart Institute Foundation
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Saphenous Vein Graft Atherosclerosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alirocumab 150 MG/ML subcutaneous injection
Arm Type
Active Comparator
Arm Description
Alirocumab 150 mg subcutaneously every 2 weeks
Arm Title
Matching Placebo subcutaneous injection
Arm Type
Placebo Comparator
Arm Description
Matching placebo subcutaneously every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Alirocumab 150 MG/ML subcutaneous injection
Other Intervention Name(s)
Praluent, Study Drug
Intervention Description
Single-dose, pre-filled, disposable, subcutaneous injection pen
Intervention Type
Drug
Intervention Name(s)
Matching Placebo subcutaneous injection
Other Intervention Name(s)
Placebo, Study Drug
Intervention Description
Single-dose, pre-filled, disposable, subcutaneous injection pen
Primary Outcome Measure Information:
Title
Nominal change in intermediate SVG lesion percent atheroma volume (PAV) from baseline to 78 weeks post randomization, as assessed by intravascular ultrasonography (IVUS).
Description
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.
Time Frame
78 weeks
Secondary Outcome Measure Information:
Title
Nominal change in TAV and normalized TAV of an intermediate SVG lesion from baseline to 78 weeks
Description
evaluate the effect of alirocumab on the change in total and normalized total atheroma volume (TAV) of an intermediate SVG lesion
Time Frame
78 weeks
Title
Angiographic failure of target SVG lesion from baseline to 78 weeks.
Description
To evaluate the effect of alirocumab on the incidence of angiographic failure of an intermediate target SVG lesion.
Time Frame
78 weeks
Title
Incidence of target SVG failure and major adverse cardiac events.
Description
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.
Time Frame
Randomization to 80 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emmanouil S Brilakis, MD, PhD
Organizational Affiliation
Minneapolis Heart Institute and Foundation/ Abbott Northwestern Hospital-Allina Health
Official's Role
Study Chair
Facility Information:
Facility Name
San Francisco VA Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Facility Name
Atlanta VA Medical Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Minneapolis Heart Institute/ Abbott North Western Hospital-Allina Health
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Dallas VA Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial

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