A randomized controlled, phase 2 trial of the viral serpin Serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention

Circ Cardiovasc Interv. 2010 Dec;3(6):543-8. doi: 10.1161/CIRCINTERVENTIONS.110.953885. Epub 2010 Nov 9.


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: http://www.clinicaltrials.gov. Unique identifier: NCT00243308.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / surgery*
  • Adult
  • Aged
  • Angioplasty, Balloon, Coronary / methods*
  • Biomarkers
  • Double-Blind Method
  • Female
  • Humans
  • Inflammation / etiology
  • Male
  • Middle Aged
  • Myocardium / pathology
  • Necrosis
  • Serine Proteinase Inhibitors / therapeutic use*
  • Serpins / adverse effects
  • Serpins / therapeutic use*
  • Ultrasonography, Interventional


  • Biomarkers
  • Serine Proteinase Inhibitors
  • Serpins

Associated data

  • ClinicalTrials.gov/NCT00243308