TY - JOUR
T1 - The Study of LoSmapimod treatment on inflammation and InfarCtSizE (SOLSTICE)
T2 - Design and rationale
AU - Melloni, Chiara
AU - Sprecher, Dennis L.
AU - Sarov-Blat, Lea
AU - Patel, Manesh R.
AU - Heitner, John F.
AU - Hamm, Christian W.
AU - Aylward, Philip
AU - Tanguay, Jean Francois
AU - Dewinter, Robbert J.
AU - Marber, Michael S.
AU - Lerman, Amir
AU - Hasselblad, Vic
AU - Granger, Christopher B.
AU - Newby, L. Kristin
N1 - Funding Information:
The SOLSTICE trial was funded by GSK. No extramural funding was used to support this work. The authors are solely responsible for the drafting and editing of the manuscript and its final contents. An Executive Steering Committee of academic representatives in collaboration with GSK scientists designed the study and developed the protocol. Academic and operational leadership and North American site management and clinical events classification were the responsibilities of the Duke Clinical Research Institute (DCRI). Core laboratory services were provided by Quest Diagnostics (Valencia, CA). GlaxoSmithKline was responsible for data management and database development, site management outside North America, safety monitoring, and expedited reporting functions. An independent data monitoring committee was used to ensure patient safety and help preserve the scientific validity of the study.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ahj.2012.07.030
DO - 10.1016/j.ahj.2012.07.030
M3 - Article
C2 - 23137494
AN - SCOPUS:84868602480
SN - 0002-8703
VL - 164
SP - 646-e3
JO - American heart journal
JF - American heart journal
IS - 5
ER -