Pexelizumab for the Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery Study - PRIMO-CABG

Description:

The goal of the trial was to evaluate if treatment with pexelizumab will be associated with a reduction in death or myocardial infarction (MI) at 30 days compared with placebo among patients undergoing coronary artery bypass graft (CABG) surgery.

Hypothesis:

Treatment with pexelizumab will be associated with a reduction in 30-day death or MI compared with placebo among patients undergoing CABG surgery.

Study Design

Study Design:

Patients Enrolled: 3,099
Mean Follow Up: 180 days

Patient Populations:

Undergoing CABG surgery with cardiopulmonary bypass with or without concomitant valve surgery

Primary Endpoints:

Death or MI at 30 days in the CABG-only cohort

Secondary Endpoints:

Death or MI at 30 days in all patients (CABG-only and CABG + valve cohorts), death or MI at four days in CABG-only cohort and all patients, and death at 180 days

Drug/Procedures Used:

Patients undergoing CABG with or without concomitant valve surgery were randomized to pexelizumab (bolus + 24 hour infusion; n=1,553) or matching placebo (n=1,546).

Principal Findings:

Pexelizumab treatment was associated with a reduction in periprocedural MI versus control (8.4% vs 11.1%, p=0.01). Death or MI at four days occurred less frequently in the pexelizumab arm compared with placebo in both the all-patient analysis (9.1% vs. 11.9%, relative risk reduction [RRR] 24%, p=0.008) and the cohort of patients who underwent CABG only (7.4% vs. 10.0%, RRR 26%, p=0.014).

Death or MI by 30 days remained lower in the pexelizumab arm in the all-patient analysis (11.5% vs. 14.0%, p=0.030), but did not reach statistical significance in the primary endpoint analysis in the CABG-only cohort (9.8% vs. 11.8%, p=0.069). In the subgroup of patients with >1 cardiac risk factor, death, or MI at 30 days was lower in the pexelizumab arm in the CABG-only patients (11.7% vs. 16.3%, RRR 28%, p=0.003).

Mortality through 180 days trended lower in the pexelizumab arm, but did not reach statistical significance (p=0.2). Event-free (death or MI) survival through 180 days was higher in the pexelizumab arm vs placebo (RRR 17%, p=0.03). There were no differences in the frequency of adverse events between treatment arms, including infection.

Interpretation:

Among patients undergoing CABG surgery, treatment with pexelizumab was not associated with a significant reduction in the primary endpoint of death or MI at 30-day follow-up compared with placebo, but was associated with reductions in death or MI at four days and periprocedural MI. Additionally, a significant reduction was observed when including the entire study cohort (CABG only + CABG/valve patients). These benefits were maintained through 6 months. The PRIMO-CABG trial was the first large-scale randomized trial to evaluate the anti-inflammatory agent pexelizumab, a terminal complement inhibitor, in patients undergoing CABG.

References:

Verrier ED, et al. Terminal Complement Blockade With Pexelizumab During Coronary Artery Bypass Graft Surgery Requiring Cardiopulmonary Bypass. JAMA. 2004;291:2319-2327.

Presented by Dr. Edward D. Verrier at the November 2003 American Heart Association Annual Scientific Sessions, Orlando, FL.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Novel Agents

Keywords: Antibodies, Monoclonal, Humanized, Complement System Proteins, Myocardial Infarction, Follow-Up Studies, Saphenous Vein, Risk Factors, Cardiopulmonary Bypass, Coronary Artery Bypass, Single-Chain Antibodies


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