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Completed

NCT Number: NCT02145468

A Phase 3 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 (LATITUDE-TIMI 60)

Losmapimod is a new anti-inflammatory medication which potentially may benefit patients with Acute Coronary Syndrome, (ACS), a condition which includes heart attack. There is a growing understanding that the inflammatory response to ACS is integral to the subsequent evolution of plaque instability. Losmapimod inhibits p38 mitogen activated protein kinase (MAPK), an enzyme which may play a central role in inflammation in the setting of heart attack. Inhibition of p38 MAPK may stabilize atherosclerotic plaques, reduce the risk of subsequent plaque rupture, indirectly improve vascular function and prevent subsequent thrombosis, and thus reduce infarct size and the risk of subsequent cardiac events. This study will test whether losmapimod can safely reduce the risk of a subsequent cardiovascular event (such as death, heart attack, or near heart attack requiring urgent treatment ) when started immediately after ACS (specifically, heart attack). Patients who present with heart attack and qualify for the study will be randomly assigned to receive 3 months treatment with either losmapimod twice daily or placebo, which will be administered in addition to the usual standard of care therapies for heart attack. Following the in-hospital period, subjects will return for outpatient visits at 4 and 12 weeks, as well as a follow up visit at 24 weeks.

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Key information

Conditions

Acute Coronary Syndrome Cardiovascular Diseases Heart Diseases Infarction Ischemia Myocardial Infarction Myocardial Ischemia Necrosis Non-ST Elevated Myocardial Infarction Pathologic Processes Pathological Conditions, Signs and Symptoms ST Elevation Myocardial Infarction Vascular Diseases

Age range

35 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

GSK Investigational Site, Quilmes, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed written informed consent
  • Men or women at least 35 years old. Women must be post-menopausal or using a highly effective method for avoidance of pregnancy
  • Hospitalization for NSTEMI or STEMI (Universal Definition Type 1 MI)
  • With the following timing of symptoms: NSTEMI: Presence of ischemic symptoms (>=5 minutes) at rest within 24 hours prior to randomization (may include qualifying episode). STEMI: Onset of qualifying ischemic symptoms within 12 hours of randomization.
  • At least one of the following
  • Age >=60 years at randomization.
  • Myocardial infarction prior to the qualifying ACS event
  • CABG prior to qualifying ACS event.
  • NSTEMI with new ischemic ST-segment depression >= 0.1 mV in >= 2 contiguous leads.
  • Diabetes mellitus requiring pharmacotherapy.
  • Coexistent clinically diagnosed arterial disease

Exclusion criteria

  • Unable to be randomized prior to coronary revascularization or fibrinolysis for the qualifying MI.
  • Current severe heart failure or shock
  • Ongoing clinical instability
  • History of chronic liver disease
  • Known severe renal impairment
  • Any condition, other than vascular disease, with life expectancy <1 year that might prevent the subject from completing the study.
  • Known active tuberculosis, HIV, active opportunistic or life threatening infections.
  • Vaccination with a live attenuated vaccine within 6 weeks of randomization.
  • Concomitant use of cytotoxic chemotherapy for cancer or known ongoing or anticipated use of chronic severe immunosuppressive agents
  • Positive pregnancy test or is known to be pregnant or lactating
  • Known alcohol or drug abuse within the past 6 months
  • Any current mental condition, which may affect study compliance or prevent understanding of the aims, investigational procedures or possible consequences of the study.
  • Participation in a study of an investigational medication within the past 30 days.
  • Anticipated inability to comply with any study procedures, including participation in study visits according to the visit schedule through 24 weeks.
  • Use of another investigational product within 30 days or 5 half-lives (whichever is longer) or according to local regulations, or currently participating in a study of an investigational device. Subjects must be randomized only one time in this investigational study
  • Any other reason the investigator deems the subject to be unsuitable for the study

Treatment and study plan

Losmapimod 7.5 mg twice daily

Drug

Subjects will receive Losmapimod 7.5 mg as film-coated, round, plain faced tablets.

Other names: GW856553

Placebo twice daily

Drug

Subjects will receive placebo as film-coated, round, plain faced tablets.

Standard therapy

Drug

Subjects will receive standard therapy consistent with the appropriate guidelines from professional societies. The standard therapy includes nitrates, morphine sulfate, beta adrenergic blockers, renin-angiotensin aldosterone inhibitors, other anti-ischemic therapies, and analgesic therapy.

Primary outcomes

  1. Number of Participants With First Occurrence of Major Adverse Cardiovascular Events (MACE) Through Week 12

    Time frame: Up to 12 weeks

    The primary efficacy endpoint is the composite measure of adjudicated MACE that includes the time to first occurrence of CV death (death due to a cardiovascular cause), MI or SRI-UR (Severe Recurrent Ischemia requiring Urgent coronary artery Revascularization). Death for which the Clinical Events Committee (CEC) or investigator were unable to establish cause were analyzed as CV deaths.

Secondary outcomes

  1. Number of Participants With First Occurrence of MACE Through Week 24

    Time frame: Up to Week 24

    Number of participants with first occurrence of MACE through Week 24 including CV death, MI or SRI-UR are presented. Death for which the CEC or investigator were unable to establish cause were analyzed as CV deaths.

  2. Number of Participants With First Occurrence of the Composite of CV Death or MI up to Week 12 and Week 24

    Time frame: Week 12 and Week 24

    Week 12 results are considered the principal secondary endpoint. Number of participants with first occurrence of the composite of CV death or MI up to Week 12 and Week 24 are summarized.

  3. Number of Participants With First Occurrence of the Composite of CV Death, MI or Hospitalization for Heart Failure (HF) up to Week 12 and Week 24.

    Time frame: Week 12 and Week 24

    Number of participants with first occurrence of the composite of CV death, MI or hospitalization for HF up to Week 12 and Week 24 are presented.

  4. Number of Participants With First Occurrence of the Expanded Composite of Arterial CV Events Defined as CV Death, MI, SRI-UR or Stroke Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the expanded composite of arterial CV events defined as CV death, MI, SRI-UR or stroke through to Week 12 and Week 24 are presented.

  5. Number of Participants With First Occurrence of the Composite of Coronary Events Defined as CHD Death, MI, SRI-UR or Any Unplanned Coronary Artery Revascularization Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of coronary events defined as coronary heart disease (CHD) death, MI, SRI-UR or any unplanned coronary artery revascularization through to Week 12 and Week 24 are presented.

  6. Number of Participants With First Occurrence of the Composite of CV Death or Hospitalization for HF Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of CV death or hospitalization for HF through to Week 12 and Week 24 are presented.

  7. Number of Participants With First Occurrence of the Composite of CV Death, MI or Stroke Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of CV death, MI or stroke through to Week 12 and Week 24 are presented.

  8. Number of Participants With First Occurrence of the Expanded Composite of CV Death, MI, SRI-UR, Stroke or Hospitalization for HF Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the expanded composite of CV death, MI, SRI-UR, stroke or hospitalization for HF through to Week 12 and Week 24 are presented.

  9. Number of Participants With First Occurrence of the Composite of CHD Death, MI or SRI-UR Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of CHD death, MI or SRI-UR through to Week 12 and Week 24 are presented.

  10. Number of Participants With First Occurrence of the Composite of CHD Death or MI Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of CHD death or MI through to Week 12 and Week 24 are presented.

  11. Number of Participants With First Occurrence of the Composite of All-cause Death, MI or SRI-UR Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of all-cause death, MI or SRI-UR through to Week 12 and Week 24 are presented.

  12. Number of Participants With First Occurrence of the Composite of All-cause Death or MI Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of all-cause death or MI through to Week 12 and Week 24 are presented.

  13. Number of Participants With First Occurrence of the Composite of CV Death, Type I (Spontaneous) MI or SRI-UR Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of CV death, type I (spontaneous) MI or SRI-UR through to Week 12 and Week 24 are presented.

  14. Number of Participants With First Occurrence of the Composite of CV Death or Type I (Spontaneous) MI Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of the composite of CV death or type I (spontaneous) MI through to Week 12 and Week 24 are presented.

  15. Number of Participants With First Occurrence of Definite or Probable Stent Thrombosis Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24 are presented. Participants receiving stent prior to randomization or during the study prior to Week 12 were included.

  16. Number of Participants Re-hospitalized Within 30 Days of Discharge

    Time frame: Within up to 30 days of post discharge

    Participants who had a death or re-hospitalization within 30 days of discharge, plus participants who were never discharged from the initial hospitalization were included.

  17. Number of Participants With All-cause Mortality Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with all-cause mortality through to Week 12 and Week 24 are presented.

  18. Number of Participants With CV Death Events Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with CV death events through to Week 12 and Week 24 are presented.

  19. Number of Participants With CHD Death Events Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with CHD death events through to Week 12 and Week 24 are presented.

  20. Number of Participants With First Occurrence of Myocardial Infarction (Fatal and Non-fatal) Events Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of myocardial infarction (fatal and non-fatal) events through to Week 12 and Week 24 are presented.

  21. Number of Participants With First Occurrence of Type I (Spontaneous) MI Events Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24 are presented.

  22. Number of Participants With First Occurrence of SRI-UR Events Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24 are presented.

  23. Number of Participants With First Occurrence of Stroke (Fatal and Non-fatal) Events Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24 are presented.

  24. Number of Participants With First Occurrence of Hospitalization for HF Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24 are presented.

  25. Number of Participants With First Occurrence of Any Unplanned Coronary Revascularization Through to Week 12 and Week 24

    Time frame: Week 12, Week 24

    Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24 are presented.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Collaborators

  • The TIMI Study Group

Registry information

Official study title

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.

Acronym: LATITUDE

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
May 23, 2014
Registry last updated
Jun 2, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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