NCT00099788

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6,560

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Oct 2004

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2004

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

December 21, 2004

Completed
Same day until next milestone

First Posted

Study publicly available on registry

December 21, 2004

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2007

Completed
Last Updated

November 26, 2009

Status Verified

November 1, 2009

Enrollment Period

2.3 years

First QC Date

December 21, 2004

Last Update Submit

November 24, 2009

Conditions

Myocardial Ischemia

Keywords

Acute Coronary SyndromeMyocardial InfarctionHeart AttackAnginaChest painIschemiaNon-ST Elevation Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (1)

  • 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.

    First occurrence

Secondary Outcomes (1)

  • 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.

    First occurence

Study Arms (2)

1

EXPERIMENTAL

Ranolazine

Drug: Ranolazine

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

RanolazineDRUG

IV to oral transition.

Also known as: Ranexa
1
PlaceboDRUG

IV to oral transition.

2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The TIMI Study Group

Boston, Massachusetts, 02115, United States

Location

Related Publications (15)

  • 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.

    PMID: 16781216BACKGROUND

  • 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.

    PMID: 33840228DERIVED

  • 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.

    PMID: 26059896DERIVED

  • 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.

    PMID: 25210025DERIVED

  • 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.

    PMID: 24852915DERIVED

  • 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.

    PMID: 24530676DERIVED

  • 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.

    PMID: 24481910DERIVED

  • 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.

    PMID: 20644019DERIVED

  • 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.

    PMID: 20385930DERIVED

  • 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.

    PMID: 20357382DERIVED

  • 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.

    PMID: 20298924DERIVED

  • 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.

    PMID: 19389561DERIVED

  • 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.

    PMID: 19371824DERIVED

  • 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.

    PMID: 19349325DERIVED

  • 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.

    PMID: 17456819DERIVED

Related Links

MeSH Terms

Conditions

Myocardial IschemiaAcute Coronary SyndromeMyocardial InfarctionAngina PectorisChest PainIschemia

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisPainNeurologic ManifestationsSigns and Symptoms

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • David A Morrow, MD

    The TIMI Study Group

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

December 21, 2004

First Posted

December 21, 2004

Study Start

October 1, 2004

Primary Completion

February 1, 2007

Study Completion

February 1, 2007

Last Updated

November 26, 2009

Record last verified: 2009-11

Locations

US(1)