MULTivessel Immediate Versus STAged RevaScularization in Acute Myocardial Infarction -The MULTISTARS AMI Trial (MULTISTARS AMI)

• ClinicalTrials.gov Identifier: NCT03135275
• Recruitment Status: Completed
• First Posted: May 1, 2017
• Last Update Posted: January 11, 2024
• Sponsor: University of Zurich
• Information provided by (Responsible Party): University of Zurich

Tracking Information

• First Submitted Date: April 10, 2017
• First Posted Date: May 1, 2017
• Last Update Posted Date: January 11, 2024
• Actual Study Start Date: October 2016
• Actual Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 12, 2019): The primary outcome measure is a composite of all-cause death, non-fatal myocardial infarction, unplanned ischemia-driven revascularization, hospitalization for heart failure, and stroke at 1 year [ Time Frame: 1-year ]
• Original Primary Outcome Measures (submitted: April 25, 2017): The composite endpoint of all cause of death, non-fatal myocardial infarction, unplanned ischemia-driven coronary revascularization [ Time Frame: 1-year ]

Current Secondary Outcome Measures (submitted: October 5, 2021)

• All-cause death, non-fatal myocardial infarction, unplanned ischemia-driven revascularization, hospitalization for heart failure, and stroke [ Time Frame: 6 months ]
  Primary endpoint
• All-cause death [ Time Frame: 6 months, 1 year ]
  Single components of the primary endpoint
• Non-fatal myocardial infarction [ Time Frame: 6 months, 1 year ]
  Single components of the primary endpoint
• Unplanned ischemia-driven revascularization [ Time Frame: 6 months, 1 year ]
  Single components of the primary endpoint
• Hospitalization for heart failure [ Time Frame: 6 months, 1 year ]
  Single components of the primary endpoint
• Stroke [ Time Frame: 6 months, 1 year ]
  Single components of the primary endpoint
• Target lesion revascularization (TLR) [ Time Frame: 6 months, 1 year ]
• Target vessel revascularization (TVR) [ Time Frame: 6 months, 1 year ]
• Non-cardiovascular death [ Time Frame: 6 months, 1 year ]
• Cardiac death [ Time Frame: 6 months, 1 year ]
• Cardiovascular death [ Time Frame: 6 months, 1 year ]
• Cardiac death or myocardial infarction [ Time Frame: 6 months, 1 year ]
• All-cause death or myocardial infarction [ Time Frame: 6 months, 1 year ]
• Stent thrombosis [ Time Frame: 6 months, 1 year ]
• Acute renal insufficiency or dialysis [ Time Frame: 6 months, 1 year ]
• Procedural success [ Time Frame: 6 months, 1 year ]
• Bleeding event (BARC definition) [ Time Frame: 6 months, 1 year ]
• Quality of life (EQ-5D questionnaire) [ Time Frame: 6 months, 1 year ]

Original Secondary Outcome Measures (submitted: April 25, 2017)

• Target Lesion Revascularization (TLR) [ Time Frame: 1 year ]
• Target Vessel Revascularization (TVR) [ Time Frame: 1-year ]
• All revascularizations [ Time Frame: 1-year ]
• Target Vessel Failure (TVF) [ Time Frame: 1-year ]
• Myocardial infarction (Q-wave and non-Q-wave) [ Time Frame: 1-year ]
• Cardiac death [ Time Frame: 1-year ]
• Non cardiac death [ Time Frame: 1-year ]
• All cause of death [ Time Frame: 1-year ]
• Cardiac death or myocardial infarction [ Time Frame: 1-year ]
• All cause of death or myocardial infarction [ Time Frame: 1-year ]
• Stent thrombosis [ Time Frame: 1-year ]
• Stroke [ Time Frame: 1-year ]
• Hospitalization for heart failure [ Time Frame: 1-year ]
• Dialysis or acute renal insufficiency [ Time Frame: 1-year ]
• Bleeding (BARC classification) [ Time Frame: 1-year ]
• The composite endpoint of all cause of death, non-fatal myocardial infarction, unplanned ischemia-driven coronary revascularization [ Time Frame: 30 days ]
• The composite endpoint of all cause of death, non-fatal myocardial infarction, unplanned ischemia-driven coronary revascularization [ Time Frame: 3 months ]
• The composite endpoint of all cause of death, non-fatal myocardial infarction, unplanned ischemia-driven coronary revascularization [ Time Frame: 6 months ]

• Current Other Pre-specified Outcome Measures (submitted: September 12, 2019): Cost-effectiveness analysis [ Time Frame: 1 year ]
• Original Other Pre-specified Outcome Measures (submitted: April 25, 2017): Cost-effectiveness analysis [ Time Frame: 1-year ]

Descriptive Information

• Brief Title: MULTivessel Immediate Versus STAged RevaScularization in Acute Myocardial Infarction -The MULTISTARS AMI Trial
• Official Title: MULTivessel Immediate Versus STAged RevaScularization in Acute Myocardial Infarction - The MULTISTARS AMI Trial
• Brief Summary: The primary objective of the trial is to compare, in patients presenting with ST segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD), the safety and efficacy of immediate complete revascularization of all significant coronary lesions versus culprit vessel only revascularization and staged percutaneous coronary intervention (PCI) of all significant coronary lesions (within 19 to 45 days), in a non-inferiority trial using a third generation, biodegradable-polymer, everolimus-eluting stent.

Detailed Description

An investigator-initiated, randomized, multicenter, two-arm, open-label study of consecutive patients presenting with STEMI and MVD in stable hemodynamic conditions, undergoing after successful PCI of the culprit lesion either (1:1 randomization) immediate revascularization of all additional target lesions during the index procedure or staged PCI of all additional target lesions (within 19 to 45 days) using the Boston Scientific Synergy™ stent.

The goal of this trial is to compare two treatment strategies that are currently performed in clinical practice: immediate complete revascularization versus staged complete revascularization in patients with STEMI and MVD.

Patients randomized to immediate complete revascularization will have treated during the index procedure, after revascularization of the culprit lesion, all significant non-culprit coronary lesions.

Patients randomized to staged complete revascularization will have treated during the index procedure only the culprit lesion, and they will be hospitalized after 19-45 days for complete revascularization of all significant non-culprit coronary lesions.

For both groups, lesion are considered significant when causing a ≥70% diameter stenosis by visual estimation in at least two projections on the coronary angiogram.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• ST-elevation Myocardial Infarction
• Multivessel Coronary Disease

Intervention

• Procedure: Staged complete PCI
  During the index procedure, patients will have treated with primary PCI the culprit lesion only. Patients will be hospitalized again after 19-45 days to undergo PCI of all the other significant coronary lesions. All the revascularizations will be performed with Synergy™ stent.
• Procedure: Immediate complete PCI
  During the index procedure, patients will have treated with primary PCI the culprit lesion, as well as all the other significant coronary lesions. All the revascularizations will be performed with Synergy™ stent.
• Device: Synergy™ stent
  Bioabsorbable Polymer Drug-Eluting Stent

Study Arms

• Active Comparator: Staged complete PCI
  Patients randomized to staged complete PCI will have treated during the index admission only the culprit lesion and they will be hospitalized after 19-45 days, to complete the coronary revascularization on all the other significant coronary lesions. All the revascularizations will be performed with Synergy™ stent.
  Interventions:

  • Procedure: Staged complete PCI
  • Device: Synergy™ stent
• Experimental: Immediate complete PCI
  Patients randomized to immediate complete PCI will have treated immediately after the revascularization of the culprit lesion during the index procedure all the other significant coronary lesions. All the revascularizations will be performed with Synergy™ stent.
  Interventions:

  • Procedure: Immediate complete PCI
  • Device: Synergy™ stent

Publications *

• Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, Berry C, Oldroyd KG; PRAMI Investigators. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013 Sep 19;369(12):1115-23. doi: 10.1056/NEJMoa1305520. Epub 2013 Sep 1.
• Gershlick AH, Khan JN, Kelly DJ, Greenwood JP, Sasikaran T, Curzen N, Blackman DJ, Dalby M, Fairbrother KL, Banya W, Wang D, Flather M, Hetherington SL, Kelion AD, Talwar S, Gunning M, Hall R, Swanton H, McCann GP. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. J Am Coll Cardiol. 2015 Mar 17;65(10):963-72. doi: 10.1016/j.jacc.2014.12.038.
• Engstrom T, Kelbaek H, Helqvist S, Hofsten DE, Klovgaard L, Holmvang L, Jorgensen E, Pedersen F, Saunamaki K, Clemmensen P, De Backer O, Ravkilde J, Tilsted HH, Villadsen AB, Aaroe J, Jensen SE, Raungaard B, Kober L; DANAMI-3-PRIMULTI Investigators. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3-PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015 Aug 15;386(9994):665-71. doi: 10.1016/s0140-6736(15)60648-1.
• Kornowski R, Mehran R, Dangas G, Nikolsky E, Assali A, Claessen BE, Gersh BJ, Wong SC, Witzenbichler B, Guagliumi G, Dudek D, Fahy M, Lansky AJ, Stone GW; HORIZONS-AMI Trial Investigators. Prognostic impact of staged versus "one-time" multivessel percutaneous intervention in acute myocardial infarction: analysis from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll Cardiol. 2011 Aug 9;58(7):704-11. doi: 10.1016/j.jacc.2011.02.071.
• Cavender MA, Milford-Beland S, Roe MT, Peterson ED, Weintraub WS, Rao SV. Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry). Am J Cardiol. 2009 Aug 15;104(4):507-13. doi: 10.1016/j.amjcard.2009.04.016. Epub 2009 Jun 18.
• Widimsky P, Holmes DR Jr. How to treat patients with ST-elevation acute myocardial infarction and multi-vessel disease? Eur Heart J. 2011 Feb;32(4):396-403. doi: 10.1093/eurheartj/ehq410. Epub 2010 Nov 30.
• Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC); Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619. doi: 10.1093/eurheartj/ehs215. Epub 2012 Aug 24. No abstract available.
• Authors/Task Force members; Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. No abstract available.
• Sabate M, Raber L, Heg D, Brugaletta S, Kelbaek H, Cequier A, Ostojic M, Iniguez A, Tuller D, Serra A, Baumbach A, von Birgelen C, Hernandez-Antolin R, Roffi M, Mainar V, Valgimigli M, Serruys PW, Juni P, Windecker S. Comparison of newer-generation drug-eluting with bare-metal stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trials. JACC Cardiovasc Interv. 2014 Jan;7(1):55-63. doi: 10.1016/j.jcin.2013.07.012. Epub 2013 Dec 11.
• Stahli BE, Varbella F, Linke A, Schwarz B, Felix SB, Seiffert M, Kesterke R, Nordbeck P, Witzenbichler B, Lang IM, Kessler M, Valina C, Dibra A, Rohla M, Moccetti M, Vercellino M, Gaede L, Bott-Flugel L, Jakob P, Stehli J, Candreva A, Templin C, Schindler M, Wischnewsky M, Zanda G, Quadri G, Mangner N, Toma A, Magnani G, Clemmensen P, Luscher TF, Munzel T, Schulze PC, Laugwitz KL, Rottbauer W, Huber K, Neumann FJ, Schneider S, Weidinger F, Achenbach S, Richardt G, Kastrati A, Ford I, Maier W, Ruschitzka F; MULTISTARS AMI Investigators. Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med. 2023 Oct 12;389(15):1368-1379. doi: 10.1056/NEJMoa2307823. Epub 2023 Aug 27.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: April 2, 2020): 840
• Original Estimated Enrollment (submitted: April 25, 2017): 1200
• Actual Study Completion Date: May 2023
• Actual Primary Completion Date: May 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥ 18 years
• Spontaneous acute STEMI (patients presenting within 24 hours of symptom onset)
• Suitability for PCI from femoral or radial access
• Coronary anatomy suitable for complete coronary revascularization with Synergy® stent implantation
• Identifiable culprit lesion/artery
• At least one non-culprit coronary stenosis ≥ 70% in at least two projections, in a vessel with a lumen diameter ≥2.25 - ≤5.75 mm, other than the culprit artery
• TIMI Flow 3 or TIMI flow 2 after revascularization of the culprit artery
• Stable hemodynamics at the end of the culprit vessel revascularization

Exclusion Criteria:

• Inability to give informed consent
• Cardiogenic shock
• Prolonged resuscitation >10 min
• General unsuitability for PCI
• Need for emergency CABG
• Previous CABG
• Planned hybrid revascularization
• Coronary artery dissection
• STEMI due to ST
• Previous documented allergic reaction to everolimus or to any stent material
• Severe mechanical complication of acute myocardial infarction
• Pre-existing severe renal failure (eGFR <30 mL/min) or renal replacement therapy
• Chronic total occlusion of a major coronary artery
• Left main stem stenosis ≥50% or left main stem equivalent (ostial left anterior descending and ostial circumflex stenosis ≥70%)
• In-stent restenosis
• Panned coronary, cerebrovascular, or peripheral arterial revascularization
• Planned cardiac or major surgery
• Any contraindications for dual antiplatelet therapy with aspirin and a P2Y12 Inhibitor for at least 90 days, except for patients on oral anticoagulation
• Known pregnancy at the time of inclusion
• Participation in another clinical study with an investigational product
• Life expectancy <1 year

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT03135275
• Other Study ID Numbers: MULTISTARS_USZ
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Zurich
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Zurich
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Barbara E. Stähli, MD, eMBA; University of Zurich

• PRS Account: University of Zurich
• Verification Date: January 2024