The study of LoSmapimod treatment on inflammation and InfarCtSizE (SOLSTICE): design and rationale

Am Heart J. 2012 Nov;164(5):646-653.e3. doi: 10.1016/j.ahj.2012.07.030. Epub 2012 Oct 16.

Abstract

The p38 mitogen-activated protein kinase (MAPK) is a nexus point in inflammation, sensing, and stimulating cytokine production and driving cell migration and death. In acute coronary syndromes, p38MAPK inhibition could stabilize ruptured atherosclerotic plaques, pacify active plaques, and improve microvascular function, thereby reducing infarct size and risk of subsequent cardiac events. The SOLSTICE trial is randomized, double-blind, placebo-controlled, parallel group, multicenter phase 2a study of 535 patients that evaluates the safety and efficacy of losmapimod (GW856553), a potent oral p38MAPK inhibitor, vs placebo in patients with non-ST-segment elevation myocardial infarction expected to undergo an invasive strategy. The coprimary end points are reduction in high-sensitivity C-reactive protein at 12 weeks and reduction in infarct size as assessed by troponin area under the curve at 72 hours. A key secondary end point is 72-hour and 12-week B-type natriuretic peptide levels as a measure of cardiac remodeling and ventricular strain. The primary safety assessments are serious and nonserious adverse events, results of liver function testing, and major adverse cardiac events. Cardiac magnetic resonance imaging (N = 117) and coronary flow reserve (N = 13) substudies will assess the effects of losmapimod on infarct size, myocardial function, and coronary vasoregulation. Information gained from the SOLSTICE trial will inform further testing of this agent in larger clinical trials.

Trial registration: ClinicalTrials.gov NCT00910962.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cardiac Surgical Procedures*
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / adverse effects
  • Cyclopropanes / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery
  • Patient Selection
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Research Design*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • 6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide
  • Biomarkers
  • Cyclopropanes
  • Protein Kinase Inhibitors
  • Pyridines
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • ClinicalTrials.gov/NCT00910962