Last updated: 11/08/2018 19:24:59
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)LATITUDE
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official 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.
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Allocation:
Randomized
Primary outcomes:
Number of participants with first occurrence of Major Adverse Cardiovascular Events (MACE) through Week 12
Timeframe: Up to 12 weeks
Secondary outcomes:
Number of participants with first occurrence of MACE through Week 24
Timeframe: Up to Week 24
Number of participants with first occurrence of the composite of CV death or MI up to Week 12 and Week 24
Timeframe: Week 12 and Week 24
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.
Timeframe: Week 12 and 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
Timeframe: Week 12, Week 24
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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: Week 12, Week 24
Number of participants with first occurrence of definite or probable stent thrombosis through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants re-hospitalized within 30 days of discharge
Timeframe: Within up to 30 days of post discharge
Number of participants with all-cause mortality through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants with CV death events through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants with CHD death events through to Week 12 and Week 24
Timeframe: 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
Timeframe: Week 12, Week 24
Number of participants with first occurrence of type I (spontaneous) MI events through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants with first occurrence of SRI-UR events through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants with first occurrence of stroke (fatal and non-fatal) events through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants with first occurrence of hospitalization for HF through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Number of participants with first occurrence of any unplanned coronary revascularization through to Week 12 and Week 24
Timeframe: Week 12, Week 24
Interventions:
Drug: Losmapimod 7.5 mg twice daily
Drug: Placebo twice daily
Drug: Standard therapy
Enrollment:
3503
Observational study model:
Not applicable
Primary completion date:
2015-14-12
Time perspective:
Not applicable
Clinical publications:
M L O’Donoghue, R Glaser, M A Cavender,P E Aylward, M P Bonaca, A Budaj, R Y Davies, M Dellborg, K A A Fox, J A T Gutierrez, C Hamm, R G Kiss, F Kovar, J F Kuder, KA Im, J Lepore, J L Lopez-Sendon, T Oude Ophuis, A Parkhomenko, J Shannon, J Spinar, J-F Tanguay, M Ruda, P G Steg, P Theroux, S D Wiviott, I Laws, M S Sabatine, and D A Morrow on behalf of the LATITUDE-TIMI 60 Investigators. Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction. A Randomized Clinical Trial. JAMA-J Am Med Assoc. 2016;315(15):1591-1599.
Medical condition
acute coronary syndrome
Product
losmapimod
Collaborators
The TIMI Study Group
Study date(s)
June 2014 to December 2015
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
35+ years
Accepts healthy volunteers
No
- 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
- Unable to be randomized prior to coronary revascularization or fibrinolysis for the qualifying MI.
- Current severe heart failure or shock
Inclusion and exclusion criteria
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
Trial location(s)
Location
GSK Investigational Site
Bangkok, Thailand, 10400
147.9 miles (236.6 km) away from your location
Status
Study Complete
Location
GSK Investigational Site
Bangkok, Thailand, 10700
148.6 miles (237.8 km) away from your location
Status
Study Complete
Location
GSK Investigational Site
Bangkok, Thailand, 10330
150.3 miles (240.5 km) away from your location
Status
Study Complete
Location
GSK Investigational Site
Chiangmai, Thailand, 50200
243.4 miles (389.4 km) away from your location
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2015-14-12
Actual study completion date
2015-14-12
Plain language summaries
Summary of results in plain language
Available language(s): Czech, English, Polish, French, Spanish
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
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