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A randomized controlled, phase 2 trial of the viral serpin Serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention.
MedLine Citation:
PMID:  21062996     Owner:  NLM     Status:  In-Process    
BACKGROUND: Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus-derived serpin Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Our objective was to evaluate the safety and efficacy of Serp-1 in patients with ACS undergoing percutaneous coronary intervention.
METHODS AND RESULTS: This double-blind pilot trial included 48 ACS patients undergoing percutaneous coronary intervention randomly assigned to Serp-1 at doses of 5 μg/kg (n=19) or 15 μg/kg (n=17) or to placebo (n=12). Serp-1 was given by intravenous bolus immediately before intervention and 24 and 48 hours later. Patients were assessed for safety (primary objective) and efficacy outcomes, including biomarker analysis. In-stent neointimal hyperplasia was evaluated by intravascular ultrasound at 6 months. Key safety outcomes including coagulation parameters and adverse events did not differ between Serp-1 and placebo groups. A dose-dependent reduction in troponin I levels was observed with Serp-1 at 8, 16, 24, and 54 hours (P<0.05) and in creatine kinase-MB levels at 8, 16, and 24 hours after dose (P<0.05). The composite of death, myocardial infarction, or coronary revascularization occurred in 2 of 12 patients with placebo, 5 of 19 in the low-dose group, and none of 17 patients with the high-dose (P=0.058). Intravascular ultrasound did not detect changes in neointimal hyperplasia among groups.
CONCLUSIONS: This is the first study of a viral serpin demonstrating its safety in ACS patients. The significant reduction in myocardial damage biomarkers supports further assessment of Serp-1 in ACS patients undergoing stent deployment.
CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT00243308.
Jean-Claude Tardif; Philippe L L'Allier; Jean Grégoire; Reda Ibrahim; Grant McFadden; William Kostuk; Merril Knudtson; Marino Labinaz; Ron Waksman; Carl J Pepine; Colin Macaulay; Marie-Claude Guertin; Alexandra Lucas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-09
Journal Detail:
Title:  Circulation. Cardiovascular interventions     Volume:  3     ISSN:  1941-7632     ISO Abbreviation:  Circ Cardiovasc Interv     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101499602     Medline TA:  Circ Cardiovasc Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  543-8     Citation Subset:  IM    
Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
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Comment In:
Circ Cardiovasc Interv. 2010 Dec;3(6):528-30   [PMID:  21156927 ]

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