Evidence map›Paper›PMID 27043082›Full record

Trial reportJAMA2016

Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.

Michelle L O'Donoghue, Ruchira Glaser, Matthew A Cavender, Philip E Aylward, Marc P Bonaca, Andrzej Budaj, Richard Y Davies, Mikael Dellborg, Keith A A Fox, Jorge Antonio T Gutierrez and 20 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in JAMA, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02145468 (A Clinical Outcomes Study to Compare the Incidence of Major Adverse Cardiovascular Events in Subjects Presenting With Acute Coronary Syndrome Treated With Losmapimod Compared to Placebo), which is not on this map. Cited by 132 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 5 pooled it
21.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02145468 phase3completednot on this map

A Clinical Outcomes Study to Compare the Incidence of Major Adverse Cardiovascular Events in Subjects Presenting With Acute Coronary Syndrome Treated With Losmapimod Compared to Placebo (PM1116197) LosmApimod To Inhibit p38 MAP Kinase as a TherapeUtic Target and moDify Outcomes After an Acute Coronary syndromE (LATITUDE)-TIMI 60.

TypeinterventionalSponsorGlaxoSmithKlineRan2014 to 2015Enrolled3,503ConditionsAcute Coronary SyndromeArmsLosmapimod 7.5 mg twice daily, Placebo twice daily, Standard therapy
3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 5 syntheses or guidelines pooled it, 240 citations in OpenAlex.

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72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 15 institutions in 19 countries.

Michelle L O'DonoghueTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Ruchira GlaserMetabolic Pathways and Cardiovascular Unit, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.
Matthew A CavenderTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Philip E AylwardSouth Australian Health and Medical Research Institute, Flinders University Medical Centre, Adelaide, South Australia, Australia.
Marc P BonacaTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Andrzej BudajPostgraduate Medical School, Grochowski Hospital, Warsaw, Poland.
Richard Y DaviesMetabolic Pathways and Cardiovascular Unit, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.
Mikael DellborgSahlgrenska University Hospital/Ostra and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Keith A A FoxCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland.
Jorge Antonio T GutierrezTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Christian HammKerckhoff Heart Center, Bad Nauheim, University of Giessen, Giessen, Germany.
Robert G KissDepartment of Cardiology, Military Hospital, Budapest, Hungary.
František KovarDepartment of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
Julia F KuderTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Kyung Ah ImTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
John J LeporeMetabolic Pathways and Cardiovascular Unit, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.
Jose L Lopez-SendonCardiovascular Division, University Hospital La Paz, Madrid, Spain.
Ton Oude OphuisCanisius-Wilhelmina Hospital, Nijmegen, the Netherlands.
Alexandr ParkhomenkoUkranian Strazhesko Institute of Cardiology, Kiev, Ukraine.
Jennifer B ShannonPAREXEL International, Durham, North Carolina.
Jindrich SpinarUniversity Hospital, Jihlavska, Brno, Czech Republic.
Jean-Francois TanguayMontreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
Mikhail RudaCardiology Research Center, Moscow, Russia.
P Gabriel StegDépartement Hospitalo-Universitaire FIRE, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, and Université Paris-Diderot, Paris, France.
Pierre TherouxMontreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
Stephen D WiviottTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Ian LawsMetabolic Pathways and Cardiovascular Unit, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.
Marc S SabatineTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
David A MorrowTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
LATITUDE-TIMI 60 Investigators
Pfizer (Canada) · CAAstraZeneca (Brazil) · BRGlaxoSmithKline (Brazil) · BRQuest University Canada · CATakeda (France) · FRDaiichi Sankyo (Germany) · DESanofi (France) · FRBaim Institute for Clinical Research · USBrigham and Women's Hospital · USEisai (Japan) · JPGlaxoSmithKline (India) · INGlaxoSmithKline (United States) · USMerck (Germany) · DENovartis (Switzerland) · CHThrombolysis in Myocardial Infarction Study Group · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

importancep38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes.

objectiveTo evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: LATITUDE-TIMI 60, a randomized, placebo-controlled, double-blind, parallel-group trial conducted at 322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A consisted of a leading cohort (n = 3503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22,000 patients). Patients were considered potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk.

interventionsPatients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12.

resultsIn part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%] were women), 99.1% had complete ascertainment for the primary outcome. The primary end point occurred by 12 weeks in 123 patients treated with placebo (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95% CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were 16.0% with losmapimod and 14.2% with placebo. CONCLUSIONS AND RELEVANCE: Among patients with acute MI, use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events. The results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population.

trial registrationclinicaltrials.gov Identifier: NCT02145468.

Indexed as

AgedAlgorithmsC-Reactive ProteinCyclopropanesDouble-Blind MethodDrug Administration ScheduleFemaleHospitalizationHumansMaleMiddle AgedMyocardial InfarctionMyocardial IschemiaMyocardial Revascularizationp38 Mitogen-Activated Protein KinasesProtein Kinase Inhibitors6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamideC-Reactive ProteinCyclopropanesp38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsPyridines

Identifiers

PMID27043082
OpenAlexW2337488815

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.