Back to resultsMetabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes
Primary Purpose
Myocardial Ischemia
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Ranolazine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Ischemia focused on measuring Acute Coronary Syndrome, Myocardial Infarction, Heart Attack, Angina, Chest pain, Ischemia, Non-ST Elevation Acute Coronary Syndrome
Eligibility Criteria
Inclusion Criteria: Hospitalized with non-ST elevation acute coronary syndrome Ischemic symptoms (more than or equal to 5 minutes) at rest within 48 hours of study entry At least one additional risk factor (e.g., elevated cardiac enzymes, ST-depression, diabetes) Exclusion Criteria: Persistent acute ST-segment elevation Successful revascularization during the qualifying hospitalization, prior to study entry Acute pulmonary edema, hypotension, or evidence of cardiogenic shock Clinically significant liver disease End stage kidney disease requiring dialysis Concomitant use of drugs known to prolong the QT interval, or any digitalis drugs Use at study entry of drugs that are strong inhibitors of cytochrome P450 3A4 Pregnant or lactating women, or women of child bearing potential not using an acceptable form of birth control Additional study entry criteria will be evaluated during initial screening.
Sites / Locations
- The TIMI Study Group
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Ranolazine
Placebo
Outcomes
Primary Outcome Measures
Time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction or recurrent ischemia through the end of the follow-up in non-ST elevation ACS.
Secondary Outcome Measures
Composite of cardiovascular death, myocardial infarction, or severe recurrent ischemia. Safety of long-term treatment with ranolazine compared to placebo; safety endpoints are death from any cause and symptomatic documented arrhythmia.
Full Information
NCT ID
NCT00099788
First Posted
December 21, 2004
Last Updated
November 24, 2009
Sponsor
Gilead Sciences
Collaborators
The TIMI Study Group
1. Study Identification
Unique Protocol Identification Number
NCT00099788
Brief Title
Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes
Official Title
A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multinational, Clinical Trial to Evaluate the Efficacy and Safety of Ranolazine vs Placebo in Patients With Non-ST Segment Elevation Acute Coronary Syndromes
Study Type
Interventional
2. Study Status
Record Verification Date
November 2009
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
February 2007 (Actual)
Study Completion Date
February 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Gilead Sciences
Collaborators
The TIMI Study Group
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
MERLIN-TIMI 36 is a multi-national, double-blind, randomized, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of ranolazine during acute and long-term treatment in approximately 5,500 patients with non-ST elevation acute coronary syndromes (ACS) treated with standard therapy. The primary efficacy endpoint in MERLIN-TIMI 36 is time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction or recurrent ischemia in patients with non-ST elevation ACS receiving standard therapy. The study also evaluates the safety of long-term treatment with ranolazine compared to placebo.
Detailed Description
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Skene A, McCabe CH, Braunwald E; MERLIN-TIMI 36 Investigators. Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial. Am Heart J. 2006 Jun;151(6):1186.e1-9.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Ischemia
Keywords
Acute Coronary Syndrome, Myocardial Infarction, Heart Attack, Angina, Chest pain, Ischemia, Non-ST Elevation Acute Coronary Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
6560 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Ranolazine
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa
Intervention Description
IV to oral transition.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
IV to oral transition.
Primary Outcome Measure Information:
Title
Time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction or recurrent ischemia through the end of the follow-up in non-ST elevation ACS.
Time Frame
First occurrence
Secondary Outcome Measure Information:
Title
Composite of cardiovascular death, myocardial infarction, or severe recurrent ischemia. Safety of long-term treatment with ranolazine compared to placebo; safety endpoints are death from any cause and symptomatic documented arrhythmia.
Time Frame
First occurence
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Hospitalized with non-ST elevation acute coronary syndrome
Ischemic symptoms (more than or equal to 5 minutes) at rest within 48 hours of study entry
At least one additional risk factor (e.g., elevated cardiac enzymes, ST-depression, diabetes)
Exclusion Criteria:
Persistent acute ST-segment elevation
Successful revascularization during the qualifying hospitalization, prior to study entry
Acute pulmonary edema, hypotension, or evidence of cardiogenic shock
Clinically significant liver disease
End stage kidney disease requiring dialysis
Concomitant use of drugs known to prolong the QT interval, or any digitalis drugs
Use at study entry of drugs that are strong inhibitors of cytochrome P450 3A4
Pregnant or lactating women, or women of child bearing potential not using an acceptable form of birth control
Additional study entry criteria will be evaluated during initial screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Morrow, MD
Organizational Affiliation
TIMI Study Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
The TIMI Study Group
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
16781216
Citation
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Skene A, McCabe CH, Braunwald E; MERLIN-TIMI 36 Investigators. Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial. Am Heart J. 2006 Jun;151(6):1186.e1-9. doi: 10.1016/j.ahj.2006.01.004.
Results Reference
background
PubMed Identifier
33840228
Citation
Zelniker TA, Morrow DA, Scirica BM, Furtado JD, Guo J, Mozaffarian D, Sabatine MS, O'Donoghue ML. Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36. J Am Heart Assoc. 2021 Apr 20;10(8):e017401. doi: 10.1161/JAHA.120.017401. Epub 2021 Apr 12.
Results Reference
derived
PubMed Identifier
26059896
Citation
Gutierrez JA, Karwatowska-Prokopczuk E, Murphy SA, Belardinelli L, Farzaneh-Far R, Walker G, Morrow DA, Scirica BM. Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial. Clin Cardiol. 2015 Aug;38(8):469-75. doi: 10.1002/clc.22425. Epub 2015 Jun 8.
Results Reference
derived
PubMed Identifier
25210025
Citation
Scirica BM, Belardinelli L, Chaitman BR, Waks JW, Volo S, Karwatowska-Prokopczuk E, Murphy SA, Cheng ML, Braunwald E, Morrow DA. Effect of ranolazine on atrial fibrillation in patients with non-ST elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial. Europace. 2015 Jan;17(1):32-7. doi: 10.1093/europace/euu217. Epub 2014 Sep 10.
Results Reference
derived
PubMed Identifier
24852915
Citation
Nieminen T, Scirica BM, Pegler JR, Tavares C, Pagotto VP, Kanas AF, Sobrado MF, Nearing BD, Umez-Eronini AA, Morrow DA, Belardinelli L, Verrier RL. Relation of T-wave alternans to mortality and nonsustained ventricular tachycardia in patients with non-ST-segment elevation acute coronary syndrome from the MERLIN-TIMI 36 trial of ranolazine versus placebo. Am J Cardiol. 2014 Jul 1;114(1):17-23. doi: 10.1016/j.amjcard.2014.03.056. Epub 2014 Apr 16.
Results Reference
derived
PubMed Identifier
24530676
Citation
O'Malley RG, Bonaca MP, Scirica BM, Murphy SA, Jarolim P, Sabatine MS, Braunwald E, Morrow DA. Prognostic performance of multiple biomarkers in patients with non-ST-segment elevation acute coronary syndrome: analysis from the MERLIN-TIMI 36 trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36). J Am Coll Cardiol. 2014 Apr 29;63(16):1644-53. doi: 10.1016/j.jacc.2013.12.034. Epub 2014 Feb 13. Erratum In: J Am Coll Cardiol. 2014 Jun 17;63(23):2642.
Results Reference
derived
PubMed Identifier
24481910
Citation
Rhee JW, Wiviott SD, Scirica BM, Gibson CM, Murphy SA, Bonaca MP, Morrow DA, Mega JL. Clinical features, use of evidence-based therapies, and cardiovascular outcomes among patients with chronic kidney disease following non-ST-elevation acute coronary syndrome. Clin Cardiol. 2014 Jun;37(6):350-6. doi: 10.1002/clc.22253. Epub 2014 Jan 30.
Results Reference
derived
PubMed Identifier
20644019
Citation
Scirica BM, Braunwald E, Belardinelli L, Hedgepeth CM, Spinar J, Wang W, Qin J, Karwatowska-Prokopczuk E, Verheugt FW, Morrow DA. Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: observations from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2010 Aug 3;122(5):455-62. doi: 10.1161/CIRCULATIONAHA.110.937136. Epub 2010 Jul 19.
Results Reference
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PubMed Identifier
20385930
Citation
Mega JL, Hochman JS, Scirica BM, Murphy SA, Sloan S, McCabe CH, Merlini P, Morrow DA. Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36). Circulation. 2010 Apr 27;121(16):1809-17. doi: 10.1161/CIRCULATIONAHA.109.897231. Epub 2010 Apr 12.
Results Reference
derived
PubMed Identifier
20357382
Citation
Chisholm JW, Goldfine AB, Dhalla AK, Braunwald E, Morrow DA, Karwatowska-Prokopczuk E, Belardinelli L. Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non-ST elevation acute coronary syndrome. Diabetes Care. 2010 Jun;33(6):1163-8. doi: 10.2337/dc09-2334. Epub 2010 Mar 31.
Results Reference
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PubMed Identifier
20298924
Citation
Morrow DA, Scirica BM, Sabatine MS, de Lemos JA, Murphy SA, Jarolim P, Theroux P, Bode C, Braunwald E. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2010 Mar 23;55(12):1189-1196. doi: 10.1016/j.jacc.2009.09.068.
Results Reference
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PubMed Identifier
19389561
Citation
Wilson SR, Scirica BM, Braunwald E, Murphy SA, Karwatowska-Prokopczuk E, Buros JL, Chaitman BR, Morrow DA. Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. J Am Coll Cardiol. 2009 Apr 28;53(17):1510-6. doi: 10.1016/j.jacc.2009.01.037.
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Scirica BM, Morrow DA, Budaj A, Dalby AJ, Mohanavelu S, Qin J, Aroesty J, Hedgepeth CM, Stone PH, Braunwald E. Ischemia detected on continuous electrocardiography after acute coronary syndrome: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2009 Apr 21;53(16):1411-21. doi: 10.1016/j.jacc.2008.12.053.
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PubMed Identifier
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Citation
Morrow DA, Scirica BM, Chaitman BR, McGuire DK, Murphy SA, Karwatowska-Prokopczuk E, McCabe CH, Braunwald E; MERLIN-TIMI 36 Investigators. Evaluation of the glycometabolic effects of ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized controlled trial. Circulation. 2009 Apr 21;119(15):2032-9. doi: 10.1161/CIRCULATIONAHA.107.763912. Epub 2009 Apr 6.
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Citation
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E; MERLIN-TIMI 36 Trial Investigators. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. doi: 10.1001/jama.297.16.1775.
Results Reference
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Links:
URL
http://www.timi.org
Description
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Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes
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