Clinical trial NCT00099788: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myocardial Ischemia
Keywords: Acute Coronary Syndrome
Myocardial Infarction
Heart Attack
Angina
Chest pain
Ischemia
Non-ST Elevation Acute Coronary Syndrome
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: The TIMI Study Group
First posted: 2004-12-21
Enrollment: 6560
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: First occurrence
Secondary outcomes:
measure: 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.
timeFrame: First occurence
Other outcomes:
Locations:
city: Boston
country: United States
facility: The TIMI Study Group
state: Massachusetts
Study officials:
affiliation: The TIMI Study Group
name: David A Morrow, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
citation: 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.
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.
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.