Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: combined results from the PRIMO-CABG I and II trials.

Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: combined results from the PRIMO-CABG I and II trials.

MedLine Citation:	PMID: 20880552 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	OBJECTIVE: The previous Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery I (PRIMO-CABG I) trial (n = 3099) indicated that C5 complement inhibition with pexelizumab might reduce myocardial infarction (MI) and postoperative mortality. PRIMO-CABG II was designed to investigate the safety and efficacy of terminal complement inhibition in reducing perioperative MI and mortality in patients undergoing CABG surgery who have 2 or more predefined preoperative risk factors. METHODS: PRIMO-CABG II, a randomized, double-blind, placebo-controlled trial, enrolled 4254 patients undergoing CABG with or without valve surgery at 249 hospitals in North America and Western Europe from June 2004 to July 2005. The patients were randomly assigned to receive intravenous pexelizumab or placebo. The primary composite endpoint was the incidence of death or MI within 30 days of randomization. RESULTS: The PRIMO-CABG II trial did not meet its prespecified primary endpoint of death or MI at 30 days, the secondary endpoints of death at 30 days, or the development of new or worsening congestive heart failure (relative risk 0.91, 0.82, and 1.01, respectively; P > .05). However, in a combined analysis of both pivotal trials, PRIMO-CABG I and II (n = 7353), death at 30 days was significantly reduced for the greatest risk subset (n = 2156, pexelizumab 5.7% vs placebo 8.1%, P = .024). Furthermore, this mortality reduction persisted throughout the 180-day follow-up period (pexelizumab 11.1% vs placebo 14.4%, P = .036). CONCLUSIONS: Pexelizumab was associated with a nonsignificant 6.7% reduction in the primary composite endpoint of death or MI at postoperative day 30 in CABG patients enrolled in the PRIMO-CABG II trial, despite the suggestion of a more favorable treatment effect in the previous PRIMO-CABG I trial. However, an exploratory analysis of the combined PRIMO I and II data set using an established predictive risk model showed a mortality benefit for high-risk surgical patients.

Authors:	Peter K Smith; Stanton K Shernan; John C Chen; Michel Carrier; Edward D Verrier; Peter X Adams; Thomas G Todaro; Lawrence H Muhlbaier; Jerrold H Levy;
Publication Detail:	Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-09-28
Journal Detail:	Title: The Journal of thoracic and cardiovascular surgery Volume: 142 ISSN: 1097-685X ISO Abbreviation: J. Thorac. Cardiovasc. Surg. Publication Date: 2011 Jul
Date Detail:	Created Date: 2011-06-20 Completed Date: 2011-08-19 Revised Date: 2011-08-31
Medline Journal Info:	Nlm Unique ID: 0376343 Medline TA: J Thorac Cardiovasc Surg Country: United States
Other Details:	Languages: eng Pagination: 89-98 Citation Subset: AIM; IM
Copyright Information:	Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Affiliation:	Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC 27710, USA. smith058@mc.duke.edu
Data Bank Information
Bank Name/Acc. No.:	ClinicalTrials.gov/NCT00088179
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MeSH Terms
Descriptor/Qualifier:	Adult Aged Aged, 80 and over Anti-Inflammatory Agents / administration & dosage, adverse effects, therapeutic use* Antibodies, Monoclonal / administration & dosage, adverse effects, therapeutic use* Cardiopulmonary Bypass Chi-Square Distribution Complement C5 / antagonists & inhibitors* Coronary Artery Bypass* / adverse effects, mortality Coronary Artery Disease / immunology, surgery* Double-Blind Method Europe Female Humans Infusions, Intravenous Kaplan-Meier Estimate Male Middle Aged Myocardial Infarction / immunology, mortality, prevention & control* North America Proportional Hazards Models Risk Assessment Risk Factors Single-Chain Antibodies / administration & dosage, adverse effects, therapeutic use* Time Factors Treatment Outcome
Chemical
Reg. No./Substance:	0/Anti-Inflammatory Agents; 0/Antibodies, Monoclonal; 0/Complement C5; 0/Single-Chain Antibodies; 0/h5G1.1-scFv
Investigator
Investigator/Affiliation:	Edward D Verrier / ; Michel Carrier / ; John C Chen / ; Axel Haverich / ; Jerrold H Levy / ; Kevin J Malloy / ; Christopher F Mojcik / ; Mark F Newman / ; Scott A Rollins / ; Stanton K Shernan / ; Thomas G Todaro / ; Kenneth M Taylor / ; Frans Van de Werf / ; Phillippe Menasche / ; Craig R Smith / ; David Fullerton / ; Joseph J McPhillips / ; Arshed Ali Quyyumi / ; Philip D Pulaski / ; Francis E Rosato / ; N Phillip Ross / ; William E Wilkinson / ; Kenneth Mahaffey / ; Bernard Chaitman / ; Robert Harrington / ; Kenneth Mahaffey / ; Peter Smith / ; Stuart Russell / ; Bernard Chaitman /
Comments/Corrections
Comment In:	J Thorac Cardiovasc Surg. 2011 Aug;142(2):472; author reply 473 [PMID: 21763876 ]

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