Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes (FREEDOM)

Cardiovascular Diseases Clinical Trial

Official title:

Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00086450
• Other study ID #: GCO 02-0163
• Secondary ID: U01HL071988R01 H
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 1, 2004
• Last updated: April 8, 2013
• Start date: April 2004
• Est. completion date: December 2018

Study information

• Verified date: April 2013
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare 5-year mortality rates in diabetic individuals with multivessel coronary artery disease (CAD) who undergo either coronary artery bypass grafting (CABG) surgery or percutaneous coronary stenting.

Description:

BACKGROUND:

The study addresses the critically important problem of how to best revascularize diabetic individuals with multivessel CAD. CAD and diabetes diagnoses are increasing at alarming rates, and much of the information regarding optimal revascularization comes from the Bypass Angioplasty Revascularization Investigation (BARI) study. After five years, data from the BARI study showed 15 excess deaths for every 100 diabetic participants revascularized by percutaneous coronary intervention (PCI) compared to CABG, and at 7 years there were more than 20 deaths. These findings provide compelling evidence for some physicians to conclude that diabetic patients with multivessel disease in need of revascularization are best handled by CABG. But a consensus has not yet been reached because these findings have not been uniformly confirmed by registries and other studies. With the recent introduction of coated stents that significantly reduce or eliminate restenosis, a prevailing belief is that adequate revascularization can be achieved by PCI even in diabetic individuals. New developments in percutaneous techniques should translate to improved prognosis to offset the advantage of CABG seen in the BARI study. Since these new drug eluting stents are not yet approved and are not likely to be on the market for several years, a small window of time exists to gather the evidence to support the strategy that provides optimal revascularization in diabetic individuals.

DESIGN NARRATIVE:

FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) is a multicenter, two-arm, open label, prospective, randomized superiority trial with equal allocation, of 5 years duration with a minimum of 3 years of follow-up. The main objective of the study is to evaluate whether PCI with drug-eluting stenting (PCI/DES) is more or less effective than the existing standard of care, CABG. The study population will consist of 2,400 adults with diabetes mellitus (Type 1 or Type 2) with angiographically confirmed multivessel CAD and morphology amenable to either PCI or CABG, with indication for revascularization based upon symptoms or angina and/or objective evidence of myocardial ischemia. Patients who consent will be randomized on a 1:1 basis either to CABG or multivessel stenting using drug-eluting stents, and followed at 30 days, 1 year, and then annually for at least 3 years, but up to 5 years. A registry of 2000 patients will also be recruited concurrently, comprised of eligible non-consenting patients for the randomized trial. Eligible patients will be randomized to receive either CABG or multivessel stenting using drug-eluting stents. Patients randomized to the PCI/DES arm will receive, at the discretion of the primary physician or interventionalists, either CYPHER Sirolimus eluting stent (Cordis Corporation, Warren, NJ, USA) or the TAXUS paclitaxel-eluting stent (Boston Scientific Corporation, Natick, MA, USA). However, it is intended that only one type of drug-eluting stent be used in a given patient during the course of the trial. The primary outcome of the study is the composite of all-cause mortality, nonfatal myocardial infarction, and stroke at the end of the 5-year patient accrual and follow-up period (minimum follow-up is 3 years). The main secondary endpoint that will be assessed is the 1-year major adverse cardiac and cerebrovascular event (MACCE) rates, including the first of one of the following: death, myocardial infarction, stroke, or repeat revascularization. Additional secondary endpoints include: all-cause and cardiovascular mortality at 1, 2, and 3 years; rates of individual MACCE endpoints at 30 days post-procedure; quality of life at 30 days, 6 months, and annually post-procedure; long term costs and cost-effectiveness.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1900
• Est. completion date: December 2018
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diabetes mellitus (Type 1 or Type 2), defined according to the American Diabetes Association as either:

1. presence of classic symptoms of diabetes mellitus with unequivocal elevation of plasma glucose (2-hour post-prandial or random of greater than 200 mg/dL (11mmol/L) or

2. fasting plasma glucose elevation on more than one occasion of at least 126 mg/dL (7mmol/L)

• Currently undergoing pharmacological or non-pharmacological treatment for diabetes

• Angiographically confirmed multivessel CAD [critical (greater than or equal to 70%) lesions in at least two major epicardial vessels and in at least two separate coronary artery territories (LAD, LCX, RCA)] amenable to either PCI or CABG

• Angiographic characteristics amendable to both PCI/DES and CABG

• Indication for revascularization based upon symptoms of angina and/or objective evidence of myocardial ischemia

Exclusion Criteria:

• Severe congestive heart failure (class III or IV according to New York Heart Association [NYHA] or pulmonary edema)

• Prior CABG surgery

• Prior valve surgery

• Prior PCI with stent implantation within 6 months of study entry

• Stroke within 6 months of study entry; if stroke occurred more than 6 months prior to study entry, must have significant residual neurologic involvement, as reflected in a Rankin Score of greater than 1

• Prior history of significant bleeding (within 6 months of study entry) that may occur during CABG or PCI/DES related anticoagulation

• In-stent restenosis of a target vessel

• Two or more chronic total occlusions in major coronary territories

• Left main stenosis (at least 50% diameter stenosis)

• Acute ST-elevation MI (Q-wave) within 72 hours of study entry requiring revascularization

• Abnormal creatine kinase level (greater than twice the normal limit); or abnormal CK-MB level at study entry

• Planned simultaneous surgical procedure unrelated to coronary revascularization (e.g., valve repair/replacement, aneurysmectomy, carotid endarterectomy, or carotid stent)

• Cannot undergo either CABG or PCI/DES because of a coexisting medical condition

• Significant leukopenia, neutropenia, thrombocytopenia, anemia, or known bleeding diathesis

• Intolerance to aspirin or both clopidogrel and ticlopidine

• Dementia with a score of less than 20 on the Mini Mental Status Examination (MMSE)

• Extra-cardiac illness that is expected to limit survival to less than 5 years (e.g., oxygen-dependent chronic obstructive pulmonary disease, active hepatitis, significant hepatic failure, or severe kidney disease)

• Pregnant

• Currently enrolled in another clinical trial

• Unable to attend required follow-up visits

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Heart Diseases

Intervention

Procedure:
• Coronary Artery Bypass Graft
For CABG, participants will receive general anesthesia and will have a breathing tube placed in their throat and they will be unconscious during the operation. An incision is made through the chest bone and muscle, which allows the surgeon access to the heart and diseased vessels. The surgeon will use one or more healthy vessels (either from an artery in the shoulder or a vein in the leg) and will bypass the diseased vessel with the healthy vessel(s). This bypass will provide needed blood supply to the heart.

Device:
• Percutaneous Coronary Intervention
For PCI, the participant will have two or more drug-eluting stents permanently implanted in their clogged arteries. Drug-eluting stents are coated with a drug that may prevent the disease in the vessel from coming back. The brand names of the stents used in this study are TAXUS and CYPHER. The participant will receive a local anesthetic. A small puncture will be made and a balloon-tipped catheter is introduced through the small puncture in the leg/arm and advanced through the artery to the diseased heart vessel. The balloon is then inflated to enlarge the opening in the vessel. After enlarging the vessel, the drug-eluting stent will be placed using a similar balloon catheter. This balloon will be inflated, expanding the stent and placing it in the diseased vessel. Once the stent is fully expanded, the balloon is deflated and removed, leaving the stent in place in the artery.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Valentin Fuster	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of all-cause mortality, non-fatal myocardial infarction, and stroke		Measured through Year 5	Yes
Secondary	Major MACCE rates, including the first of one of the following: death, myocardial infarction, stroke, or repeat revascularization		Measured at Year 1	Yes
Secondary	All-cause and cardiovascular mortality		Measured at Years 1, 2, and 3	Yes
Secondary	Rates of individual MACCE endpoints		Measured at Day 30	Yes
Secondary	Quality of life		Measured at Day 30, Month 6, and Year 1	No
Secondary	Long-term costs and cost-effectiveness		Measured throughout the study	No