Study Design

Study Design:

Patients Enrolled: 150
NYHA Class: NYHA class III, 96% in placebo and 5 mg/kg arm; 92% in 10 mg/kg arm
Mean Follow Up: 28 weeks
Mean Patient Age: 62 years
Female: 19%
Mean Ejection Fraction: Mean LVEF 24%

Patient Populations:

Age ≥18 years; stable NYHA class III or IV heart failure associated with a radionuclide LVEF ≤35% within 14 days; treatment with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor (or an angiotensin II receptor blocker if intolerant of ACE inhibitors) for at least 85% of the time during the prior three months. Heart failure is considered stable if none of the following occurred within two weeks before screening: change in NYHA functional class, hospitalization for heart failure, or administration of any intravenous medication for heart failure.

Exclusions:

Hemodynamically significant obstructive valvular disease, cor pulmonale, restrictive or hypertrophic cardiomyopathy, constrictive pericarditis, or congenital heart disease; acute myocardial infarction or coronary revascularization procedure within two months; likely to undergo coronary revascularization or heart transplant during the anticipated duration of the study; resuscitated from sudden death or had a therapeutic discharge of an implanted implantable cardioverter defibrillator within three months; serious infection within two months; latent tuberculosis or had tuberculosis within three years; documented human immunodeficiency virus infection; any other opportunistic infection within six months' use of infliximab or other therapeutic agents that could interfere with the actions of TNF-alpha within three months; or had received within two weeks or were likely to receive during the study any of the following: a class IC or III antiarrhythmic other than amiodarone, a calcium channel blocker other than amlodipine for hypertension or angina, a positive inotrope other than digoxin, or a nonsteroidal anti-inflammatory drug other than aspirin

Primary Endpoints:

Change in clinical status at 14 weeks. Clinical status was assessed by the clinical composite score, and patients were categorized as: 1) improved if the patient showed an improved New York Heart Association (NYHA) class or moderate or marked improvement in global assessment; 2) worse if the patient died, was hospitalized for heart failure, or had worsening NYHA class or moderate or marked worsening of the patient global assessment; or 3) unchanged.

Secondary Endpoints:

Change in inflammatory markers during the 28-week trial period; change in LVEF at 14 and 28 weeks; composite of death or hospitalization for worsening heart failure at 28 weeks; and change in Minnesota Living With Heart Failure score at 14 and 28 weeks

Drug/Procedures Used:

Potential trial participants underwent a screening evaluation two weeks before randomization. If eligible, patients were randomized in a double-blind manner to placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51). Patients were treated with the study drug immediately after randomization and at the two- and six-week visits as a two-hour intravenous infusion.

Concomitant Medications:

Beta-blockers, digoxin, and spironolactone were allowed, if started ≥3 months prior to screening and were to be continued throughout the study period. Vasodilator or nitrate use was permitted. All cardiac medication doses were to be constant for at least two weeks before and during screening.