Clinical trial NCT01399736: Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD.
Official title: Fractional Flow Reserve Guided Primary Multivessel Percutaneous Coronary Intervention to Improve Guideline Indexed Actual Standard of Care for Treatment of ST-elevation Myocardial Infarction in Patients With Multivessel Coronary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myocardial Infarction
Multivessel Coronary Artery Disease
Keywords: PCI FFR STEMI MVD
FFR guided PCI in acute STEMI patients with MVD
Lead sponsor: Maasstad Hospital
Sponsor class: OTHER
Collaborators: name: Abbott Medical Devices
First posted: 2011-07-22
Enrollment: 885
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Compare-Acute trial is a prospective randomised trial in patients with multivessel disease, who are admitted into hospital with a ST-elevation Myocardial Infarction. The purpose of the study is to compare a FFR guided multivessel PCI taking place during the primary PCI with a primary PCI of the culprit vessel only.

Patients will be enrolled after successful revascularisation of the culprit vessel. Patients that have at least one lesion with a diameter of stenosis of more than 50% on visual estimation, feasible (operators judgement) for treatment with PCI in a non-infarct related artery, will be randomised either to the FFR guided complete revascularisation arm or staged revascularisation by proven ischemia or persistence of symptoms of angina.

Approximately 885 patients will be entered in the study.

Study hypothesis: FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines.

Detailed description: Background of the study: At the moment the general opinion is divided over the way the non culprit lesions in patients presenting with STEMI should be treated. While the previous guidelines stead that these lesions should be treated in a second time ( ie not during the primary intervention) the actual guidelines do not touch this argument. The reason is that the studies where the previous guidelines were based are old. Meanwhile small sized randomised trials from EU region have proven favourable outcomes with NON infarct related artery during the primary procedure while registers (non randomised trials) from USA still recommend the staged treatment. For this reason we have decided to perform a randomised study to address this issue incorporating the state of the art diagnosis and treatment, as well as the new medical therapy and PCI techniques.

Objective of the study: FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines

Study design: Prospective, 1: 2 randomisation. FFR guided revascularisation during primary PCI (1) versus following actual guidelines (2)

Study population: All STEMI patients between 18-85 years who will be treated with primary PCI in \< 12 h (more than 12 hr if persisting pain allowed) after the onset of symptoms and have at least one stenosis of \>50% in a non-IRA judged feasible for treatment with PCI.

Intervention (if applicable): FFR-guided complete percutaneous revascularisation of all flow-limiting stenoses in the non-IRA performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to the staged revascularisation, guided by prove of ischemia or clinical judgment, as recommended from the guidelines

Primary study parameters/outcome of the study: Composite endpoint of all cause mortality non-fatal Myocardial Infarction, any Revascularisation and Stroke (MACCE) at 12 months

Eligibility criteria: Inclusion Criteria:

* All patients between 18-85 years presenting with STEMI who will be treated with primary PCI in \< 12 h after the onset of symptoms\* and have at least one stenosis of \>50% in a non-IRA on QCA or visual estimation of baseline angiography and judged feasible for treatment with PCI by the operator.

  * Patients with symptoms for more than 12 hr but ongoing angina complaints can be randomised

Exclusion Criteria:

1. Left main stem disease (stenosis \> 50%)
2. STEMI due to in-stent thrombosis
3. Chronic total occlusion of a non-IRA
4. Severe stenosis with TIMI flow ≤ II of the non-IRA artery.
5. Non-IRA stenosis not amenable for PCI treatment (operators decision)
6. Complicated IRA treatment, with one or more of the following;

   * Extravasation,
   * Permanent no re-flow after IRA treatment (TIMI flow 0-1),
   * Inability to implant a stent
7. Known severe cardiac valve dysfunction that will require surgery in the follow-up period.
8. Killip class III or IV already at presentation or at the completion of culprit lesion treatment.
9. Life expectancy of \< 2 years.
10. Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, Bivaluridin, or Everolimus and known true anaphylaxis to prior contrast media of bleeding diathesis or known coagulopathy.
11. Gastrointestinal or genitourinary bleeding within the prior 3 months,
12. Planned elective surgical procedure necessitating interruption of thienopyridines during the first 6 months post enrolment.
13. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
14. Pregnancy or planning to become pregnant any time after enrolment into this study.
15. Inability to obtain informed consent.
16. Expected lost to follow-up.

Primary outcomes:
measure: Number of Participants With the Composite Endpoint of MACCE
timeFrame: 12 months
measure: Number of Participants With Death From Any Cause
timeFrame: 12 months
measure: Number of Participants With Cardiac Death
timeFrame: 12 months
measure: Number of Participants With Spontaneous MI
timeFrame: 12 months
measure: Number of Participants With Periprocedural MI
timeFrame: 12 months
measure: Number of Participants With Revascularization - PCI
timeFrame: 12 months
measure: Number of Participants With Revascularization - CABG
timeFrame: 12 months
measure: Number of Participants With Cerebrovascular Event
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participants With Composite Endpoint of NACE (Any First Event)
timeFrame: 12 months
measure: Number of Participants With Death From Any Cause or MI
timeFrame: 12 months
measure: Number of Participants With Major Bleeding
timeFrame: 12 months
measure: Number of Participants With Any Bleeding at 12 Months
timeFrame: 12 months
measure: Number of Participants With Any Bleeding at 48 Hours
timeFrame: 48 hours
measure: Number of Participants With Hospitalization
timeFrame: 12 months
measure: Number of Participants With Revascularization
timeFrame: 12 months
measure: Number of Participants With Stent Thrombosis
timeFrame: 12 months
measure: Number of Participants With Primary Endpoint Outcome MACCE (Any First Event) at 3 Year
timeFrame: 3 year
measure: Number of Participants With All Cause Death at 3 Year
timeFrame: 3 year
measure: Number of Participants With Cardiac Death at 3 Year
timeFrame: 3 year
measure: Number of Participants With Spontaneous MI at 3 Year
timeFrame: 3 year
measure: Number of Participants With Peri-procedural MI at 3 Year
timeFrame: 3 year
measure: Number of Participants With Urgent Revascularization at 3 Year
timeFrame: 3 year
measure: Number of Participants With Elective Revascularization at 3 Year
timeFrame: 3 year
measure: Number of Participants With Cerebrovascular Event
timeFrame: 3 year
measure: Number of Participants With Composite Endpoint of NACE (Any First Event) at 3 Year
timeFrame: 3 years
measure: Number of Participants With Death From Any Cause or MI
timeFrame: 3 year
measure: Number of Participants With Major Bleeding at 3 Year
timeFrame: 3 year
measure: Number of Participants With Hospitalization
timeFrame: 3 year
measure: Number of Participants With Hospitalization at 3 Year
timeFrame: 3 year
measure: Number of Participants With Stent Thrombosis at 3 Year
timeFrame: 3 year
measure: Number of Participants With Any Bleeding at 3 Year
timeFrame: 3 year
Other outcomes:
measure: A Comparison of the Number of Patients in Both Groups With Treated Lesions With FFR ≤ 0.80 Versus Patients With Untreated Lesions With FFR ≤ 0.80;
timeFrame: 3 year
measure: Comparison of Acute Versus Staged PCI for Lesions With FFR ≤ 0.80
timeFrame: 3 year
measure: Comparison of PCI vs Medical Therapy in FFR Negative Lesions
timeFrame: 3 year
Locations:
city: Brno
country: Czechia
facility: University Hospital BRNO
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Králové
city: Liberec
country: Czechia
facility: Liberec Regional Hospital
city: Bad Krozingen
country: Germany
facility: Herz-Zentrum Bad Krozingen
city: Bad Segeberg
country: Germany
facility: Herzzentrum Bad Segeberger Klinik
city: Bremen
country: Germany
facility: Klinikum Links der Weser
city: Ingolstadt
country: Germany
facility: Medizinische Klinik IV
city: Rostock
country: Germany
facility: Medical University Rostock
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet
city: Nyíregyháza
country: Hungary
facility: Szabolcs - Szatmár - Bereg County Hospitals and University Teaching Hospital
city: Szeged
country: Hungary
facility: Szent-Györgyi Albert Klinika
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Korhaz
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Heerlen
country: Netherlands
facility: Atrium MC Parkstad
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medical center
city: Rotterdam
country: Netherlands
facility: Maasstadhospital
city: The Hague
country: Netherlands
facility: Medisch Centrum Haaglanden
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Lubin
country: Poland
facility: Miedziowe Centrum Zdrowia Lubin
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
city: Warsaw
country: Poland
facility: Kliniki Kardiologii Allenort
city: Wroclaw
country: Poland
facility: 4 Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Singapore
country: Singapore
facility: Khoo Teck Puat Hospital
city: Goteborg
country: Sweden
facility: Sahlgrenska Götheborg University Hospital
Study officials:
affiliation: Maastadhospital / MCR
name: Peter Smits, MD. PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sahlgrenska Hospital Götheborg
name: Elmir Omerovic, MD PhD
role: STUDY_CHAIR
affiliation: Herzzentrum Segeberger Kliniken
name: Gert Richardt, MD PhD
role: STUDY_CHAIR
affiliation: Herz-Zentrum Bad Krozingen
name: Franz-Josef Neumann, MD PhD
role: STUDY_CHAIR
References:
citation: Piroth Z, Fulop G, Boxma-de Klerk BM, Abdelghani M, Omerovic E, Andreka P, Fontos G, Neumann FJ, Richardt G, Smits PC. Correlation and Relative Prognostic Value of Fractional Flow Reserve and Pd/Pa of Nonculprit Lesions in ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Interv. 2022 Feb;15(2):e010796. doi: 10.1161/CIRCINTERVENTIONS.121.010796. Epub 2022 Jan 20.
citation: Wang LJ, Han S, Zhang XH, Jin YZ. Fractional flow reserve-guided complete revascularization versus culprit-only revascularization in acute ST-segment elevation myocardial infarction and multi-vessel disease patients: a meta-analysis and systematic review. BMC Cardiovasc Disord. 2019 Mar 1;19(1):49. doi: 10.1186/s12872-019-1022-6.
citation: Smits PC, Abdel-Wahab M, Neumann FJ, Boxma-de Klerk BM, Lunde K, Schotborgh CE, Piroth Z, Horak D, Wlodarczak A, Ong PJ, Hambrecht R, Angeras O, Richardt G, Omerovic E; Compare-Acute Investigators. Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction. N Engl J Med. 2017 Mar 30;376(13):1234-1244. doi: 10.1056/NEJMoa1701067. Epub 2017 Mar 18.