Azithromycin and Coronary Events Study (ACES)

To determine whether treatment with azithromycin decreases the rate of coronary heart disease events among patients with stable documented coronary artery disease.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Heart Diseases; Cardiovascular Diseases; Coronary Disease
• Intervention / Treatment: Drug: azithromycin

Detailed Description

BACKGROUND:

Cumulative evidence from past studies supports but does not prove a causal association between Chlamydia pneumoniae infection and development or progression of atherosclerotic cardiovascular disease. Evidence supporting an association raises the question of whether a causal effect of Chlamydia pneumonia infection, if present, may be ameliorated by antibiotic treatment, resulting in decreased CHD outcomes. The ACES is a randomized, double-blind, placebo-controlled study to determine whether treatment with azithromycin decreases the rate of coronary heart disease events among patients with stable documented coronary artery disease.

DESIGN NARRATIVE:

A randomized, double-blind, multicenter trial of azithromycin versus placebo among adults with documented prevalent coronary artery disease. Patients were enrolled over an 18-month period from a total of 28 centers. Following enrollment, an electrocardiogram was obtained, and patients with a prolonged QT interval were excluded. Eligible patients were then randomized to receive either placebo or azithromycin 600 milligrams orally once a week for a year. At the time of enrollment, a blood sample was obtained for C. pneumoniae antibody testing. Patients were contacted at one, three, and six weeks, and at three, six, nine, and twelve months. The patients were followed for a mean of four years for the composite primary outcome of coronary heart disease death, non-fatal myocardial infarction, hospitalization for unstable angina, and requirement for coronary artery bypass grafting or percutaneous revascularization. After the first year of the study, each patient was contacted every six months to determine the occurrence of outcomes. In addition, when available, computerized hospitalization and outpatient data were reviewed. Outcome events were classified using standardized algorithms. The relationship of antibody titer at baseline to the efficacy of azithromycin and outcome was a secondary analysis. The primary analysis was according to the intent-to-treat principle.

In addition to the therapeutic trial a serologic follow-up substudy was conducted on 25 percent of patients enrolled in the therapeutic trial. The subset of patients were randomized to obtain blood samples at three and six months, one and two years, and at the end of the study for serologies. The purpose of the substudy was to determine the effect of azithromycin on serologic titers to C. pneumoniae and to evaluate whether the occurrence of coronary heart disease events is associated with a change in antibody titer.

Protocol planning will take place for the first six months of the trial, followed by one and a half years of patient enrollment. Patient followup continues for three years after the recruitment period and the final six months will be a close out and analysis phase.

The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Men and women over the age of 18 who have stable, documented coronary artery disease (CAD). Evidence of CAD was by any one of: history of MI; greater than 50% stenosis in any coronary artery; or history of coronary revascularization procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Masking: Double

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: J. Grayston, University of Washington

Publications and helpful links

General Publications

• Jackson LA. Description and status of the azithromycin and coronary events study (ACES). J Infect Dis. 2000 Jun;181 Suppl 3:S579-81. doi: 10.1086/315628.
• Anderson JL. Infection, antibiotics, and atherothrombosis--end of the road or new beginnings? N Engl J Med. 2005 Apr 21;352(16):1706-9. doi: 10.1056/NEJMe058019. No abstract available.
• Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E, Knirsch C; ACES Investigators. Azithromycin for the secondary prevention of coronary events. N Engl J Med. 2005 Apr 21;352(16):1637-45. doi: 10.1056/NEJMoa043526.

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: October 27, 1999
• First Submitted That Met QC Criteria: October 27, 1999
• First Posted (Estimate): October 28, 1999

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: May 1, 2005

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Vascular Diseases; Myocardial Infarction; Infarction; Heart Diseases; Coronary Disease; Cardiovascular Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 120 (Tumor Vaccine Group); M01RR007122-13 (U.S. NIH Grant/Contract); M01RR000048-44 (U.S. NIH Grant/Contract); M01RR000645-34 (U.S. NIH Grant/Contract)