Aggressive Cholesterol Therapy to Inhibit Vein Graft Events After CABG (ACTIVE Trial) (ACTIVE)

• ClinicalTrials.gov Identifier: NCT01528709
• Recruitment Status: Completed
• First Posted: February 8, 2012
• Results First Posted: August 9, 2018
• Last Update Posted: September 7, 2018
• Sponsor: Boca Raton Regional Hospital
• Collaborator: Pfizer
• Information provided by (Responsible Party): Dr. Alexander Kulik, Boca Raton Regional Hospital

Study Description

Brief Summary:

During coronary artery bypass graft surgery (CABG), saphenous vein from the leg is used to bypass the atherosclerotic blockages in the arteries of the heart. Unfortunately, vein bypasses themselves develop blockages over time, a process termed saphenous vein graft disease. By lowering cholesterol levels in the blood, statin medications are used after surgery to prevent the development of atherosclerotic blockages in the vein bypasses. Recently, higher doses of statin medications have been introduced, with some studies showing that they are more effective than traditional doses when used in heart attack patients. Furthermore, laboratory tests have shown that higher doses of statin medications can slow the development of atherosclerosis. Despite these benefits, very little is known regarding the use of high-dose statin therapy after bypass surgery in humans.

The goal of this study will be to see if high-dose statin therapy will prevent the development of vein graft occlusion during the first year after bypass surgery. Patients will be randomized to receive either high-dose statin therapy or conventional moderate-dose statin therapy starting within 4 days of surgery and continuing for the duration of one year after the operation. The statin medication will be given in capsule form. During the course of this study, neither the patient nor the health care team will know which treatment each patient is receiving. One year after bypass surgery, a computed tomography (CT) coronary angiogram will be performed to evaluate the patency of the vein bypasses.

Condition or disease	Intervention/treatment	Phase
Saphenous Vein Graft Disease	Drug: Atorvastatin 80 mg daily; Drug: Atorvastatin 10 mg daily	Phase 3

Detailed Description:

The current clinical guidelines recommend treatment to achieve LDL levels <100 mg/dL after surgical coronary revascularization. However, recent studies have illustrated that even more intensive lipid reduction with high-dose statins can further improve cardiovascular outcomes. Targeting LDL levels to 70 mg/dL after CABG with intensive statin therapy may prevent the process of postoperative saphenous vein graft disease and lead to improved graft patency. Therefore, in the ACTIVE Trial, we will conduct a randomized controlled trial comparing high-dose (80 mg atorvastatin) to moderate-dose (10 mg atorvastatin)statin therapy in patients undergoing CABG with saphenous vein grafts. The effect of aggressive cholesterol therapy on the process of vein graft disease will be examined with computed tomography (CT) coronary angiography one year after CABG. This study will address the subject of postoperative high-dose statin therapy and help determine the optimal lipid-lowering strategy following CABG.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 173 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Aggressive Cholesterol Therapy to Inhibit Vein Graft Events (ACTIVE Trial): Does High-Dose Postoperative Statin Therapy Improve Graft Patency After Coronary Bypass?
• Study Start Date: March 2012
• Actual Primary Completion Date: January 2017
• Actual Study Completion Date: January 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: High-dose statin therapy; Atorvastatin 80 mg daily	Drug: Atorvastatin 80 mg daily; Atorvastatin 80 mg daily for 1 year
Active Comparator: Moderate-dose statin therapy; Atorvastatin 10 mg daily	Drug: Atorvastatin 10 mg daily; Atorvastatin 10 mg daily for 1 year

Outcome Measures

Primary Outcome Measures :

1. Saphenous Vein Graft Occlusion (Percentage of Vein Grafts Occluded) Based on CT Coronary Angiography at 1 Year [ Time Frame: 1 year after CABG ]
   Vein graft patency will be assessed in a blinded fashion by CT coronary angiography 1 year after CABG

Secondary Outcome Measures :

1. Vein Graft Stenosis 1 Year After CABG Based on CT Coronary Angiography [ Time Frame: Within 1 year after CABG ]
   Vein graft stenosis 1 year after CABG based on CT coronary angiography

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients undergoing first-time CABG with at least 1 saphenous vein graft

Exclusion Criteria:

• Redo-CABG
• Statin allergy
• Severe renal dysfunction
• Severe liver disease

Contacts and Locations

Locations

United States, Florida

Lynn Heart and Vascular Institute, Boca Raton Regional Hospital

Boca Raton, Florida, United States, 33486

Canada, Ontario

University of Ottawa Heart Institute

Ottawa, Ontario, Canada, K1Y 4W7

Sponsors and Collaborators

Boca Raton Regional Hospital

Pfizer

Investigators

• Principal Investigator: Alexander Kulik, MD MPH; Lynn Heart and Vascular Institute, Boca Raton Regional Hospital
• Principal Investigator: Marc Ruel, MD MPH; Ottawa Heart Institute Research Corporation

More Information

Publications:

Kulik A, Voisine P, Mathieu P, Masters RG, Mesana TG, Le May MR, Ruel M. Statin therapy and saphenous vein graft disease after coronary bypass surgery: analysis from the CASCADE randomized trial. Ann Thorac Surg. 2011 Oct;92(4):1284-90; discussion 1290-1. doi: 10.1016/j.athoracsur.2011.04.107.

Kulik A, Ruel M. Lipid-lowering therapy and coronary artery bypass graft surgery: what are the benefits? Curr Opin Cardiol. 2011 Nov;26(6):508-17. doi: 10.1097/HCO.0b013e32834b9fb1. Review.

Kulik A, Ruel M. Statins and coronary artery bypass graft surgery: preoperative and postoperative efficacy and safety. Expert Opin Drug Saf. 2009 Sep;8(5):559-71. doi: 10.1517/14740330903188413. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kulik A, Abreu AM, Boronat V, Ruel M. Intensive versus moderate atorvastatin therapy and one-year graft patency after CABG: Rationale and design of the ACTIVE (Aggressive Cholesterol Therapy to Inhibit Vein Graft Events) randomized controlled trial (NCT01528709). Contemp Clin Trials. 2017 Aug;59:98-104. doi: 10.1016/j.cct.2017.06.006. Epub 2017 Jun 10.

• Responsible Party: Dr. Alexander Kulik, Cardiovascular Surgeon, Boca Raton Regional Hospital
• ClinicalTrials.gov Identifier: NCT01528709
• Other Study ID Numbers: 2011.02
• First Posted: February 8, 2012
• Results First Posted: August 9, 2018
• Last Update Posted: September 7, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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.: No

Keywords provided by Dr. Alexander Kulik, Boca Raton Regional Hospital:

Statin,; CABG,; saphenous vein graft,; graft occlusion,; lipids

Additional relevant MeSH terms:

Aggression; Behavioral Symptoms; Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors