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

NCT ID: NCT01528709

Last Updated: 2018-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2017-01-31

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.

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.

Conditions

Saphenous Vein Graft Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

High-dose statin therapy

Atorvastatin 80 mg daily

Group Type: EXPERIMENTAL

Atorvastatin 80 mg daily

Intervention Type: DRUG

Atorvastatin 80 mg daily for 1 year

Moderate-dose statin therapy

Atorvastatin 10 mg daily

Group Type: ACTIVE_COMPARATOR

Atorvastatin 10 mg daily

Intervention Type: DRUG

Atorvastatin 10 mg daily for 1 year

Interventions

Atorvastatin 80 mg daily

Atorvastatin 80 mg daily for 1 year

Intervention Type: DRUG

Atorvastatin 10 mg daily

Atorvastatin 10 mg daily for 1 year

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Boca Raton Regional Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dr. Alexander Kulik

Cardiovascular Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexander Kulik, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Lynn Heart and Vascular Institute, Boca Raton Regional Hospital

Marc Ruel, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Locations

Lynn Heart and Vascular Institute, Boca Raton Regional Hospital

Boca Raton, Florida, United States

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 21958773 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21934497 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19673591 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28611006 (View on PubMed)

Other Identifiers

2011.02

Identifier Type: -

Identifier Source: org_study_id