Clinical trial NCT05599061: Treatment of Functionally Non-significant Vulnerable Plaques in Patients With Multivessel ST-elevation Myocardial Infarction The VULNERABLE Trial
Official title: Treatment of Functionally Non-significant Vulnerable Plaques in Patients With Multivessel ST-elevation Myocardial Infarction The VULNERABLE Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Coronary Disease
Ischemic Heart Disease
Keywords: Vulnerable Plaque
Optical Coherence Tomography
Fractional Flow Reserve and ST-elevation Myocardial Infarction
Lead sponsor: Fundación EPIC
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2022-10-31
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study aims to compare a preventive percutaneous coronary intervention (PCI) plus optimal medical treatment (OMT) strategy vs. OMT for treatment of non-functionally significant non-culprit lesions presenting with optical coherence tomography (OCT) findings indicative of vulnerable plaque, in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease.

Detailed description: STEMI patients with multivessel disease planned for invasive evaluation of intermediate lesions (40-69% stenosis) are initially investigated with fractional flow reserve (FFR). Patients with FFR ≤ 0.80 are considered as screening failure and treated with PCI. Patients with FFR \> 0.80 are then investigated with optical coherence tomography (OCT). Patients without OCT findings of vulnerable plaque are treated with OMT and included in the OMT registry arm. Patients presenting with OCT characteristics of vulnerable plaque are included in the randomized trial comparing PCI with stent implantation plus OMT versus OMT.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years.
* Successful revascularization of the culprit lesion in patients undergoing coronary angiography due to ST-segment elevation (\> 1mm in \> 2 contiguous leads, new left bundle branch block, or true posterior MI with ST depression of \>1mm in \>2 contiguous anterior leads) in the first 72 hours of the symptom's onset.
* Multivessel coronary disease with non-culprit lesions located in different vessels than the culprit lesion and ranging from 40 to 69% of DS (visual estimated diameter stenosis ) by visual estimate planned for FFR-guided revascularization in staged procedure (\>24 hours and \<60 days after PCI of the culprit lesion).
* Non-culprit lesions should be suitable for functional assessment with pressure wire and OCT catheter and should be suitable to be treated with a single 2.0 to 4.5 mm EES (everolimus-eluting stent ).
* Subject agrees to not participate in any other clinical trial study for a period of 4 years following the inclusion in the study.
* Informed consent signed.

Exclusion Criteria:

* Inability to provide informed consent.
* Female of childbearing potential (age \<50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy.
* Known intolerance to aspirin, heparin, everolimus, contrast material.
* Unresolved mechanical complication or cardiogenic shock at the staged procedure.
* Non-culprit study lesions located in the left main coronary artery or in coronary vessels with prior coronary revascularization (PCI or by-pass) or with distal vessel occlusion.
* Patients with long, bifurcated, severely angulated or severely calcified non-culprit study lesions non suitable to be treated with a single EES implantation.
* Asthma or known history of bronchial hyper-reactivity.
* Chronic renal dysfunction with creatinine clearance \< 45 ml/min.
* Severe comorbidities that in the opinion of the local investigators determine the patient's life expectancy \< 4 years.
* Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.

Primary outcomes:
measure: Target Vessel Failure (TVF)
timeFrame: 4 Years
Secondary outcomes:
measure: Cardiac death
timeFrame: 4 Years
measure: All-cause Death
timeFrame: 4 Years
measure: All Myocardial Infarctions
timeFrame: 4 Years
measure: Target-Vessel Myocardial Infarction
timeFrame: 4 Years
measure: Revascularizations
timeFrame: 4 Years
measure: Ischemic-driven target vessel revascularization
timeFrame: 4 Years
measure: Patient-oriented endpoint of major adverse cardiac events
timeFrame: 4 Years
measure: Target Vessel Failure (TVF)
timeFrame: 4 Years
measure: Fractional Flow Reserve (FFR)
timeFrame: 4 years
measure: Minimal lumen area by Optical Coherence Tomography (OCT)
timeFrame: 4 years
measure: Accuracy of vulnerable plaque assessment by Optical Coherence Tomography (OCT)
timeFrame: 4 years
Other outcomes:
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Albacete
country: Spain
facility: Hospital General Universitario de Albacete
city: Alicante
country: Spain
facility: Hospital General Universitario Dr.Balmis
city: Alicante
country: Spain
facility: Hospital Universitari Sant Joan D'Alacant
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital de Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta Del Mar
city: Castellón De La Plana
country: Spain
facility: Hospital General Universitario de Castellón
city: Ciudad Real
country: Spain
facility: Hospital General Universitario de Ciudad Real
city: Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia de Cordoba
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Gijón
country: Spain
facility: Hospital Universitario de Cabueñes
city: Girona
country: Spain
facility: Hospital Universitario de Girona Dr Trueta
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramon Jimenez
city: León
country: Spain
facility: Hospital Universitario de Leon
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Manises
country: Spain
facility: Hospital de Manises
city: Murcia
country: Spain
facility: Hospital Universitario Virgen Arrixaca
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Espases
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: San Sebastián
country: Spain
facility: Hospital Universitario de Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Tarragona
country: Spain
facility: Hospital Universitari Joan Xxiii
city: Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de La Candelaria
city: Torrevieja
country: Spain
facility: Hospital Universitario de Torrevieja
city: Usera
country: Spain
facility: Hospital Universitario 12 Octubre
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitari Miquel Servet
Study officials:
References:
citation: Puymirat E, Cayla G, Simon T, Steg PG, Montalescot G, Durand-Zaleski I, le Bras A, Gallet R, Khalife K, Morelle JF, Motreff P, Lemesle G, Dillinger JG, Lhermusier T, Silvain J, Roule V, Labeque JN, Range G, Ducrocq G, Cottin Y, Blanchard D, Charles Nelson A, De Bruyne B, Chatellier G, Danchin N; FLOWER-MI Study Investigators. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021 Jul 22;385(4):297-308. doi: 10.1056/NEJMoa2104650. Epub 2021 May 16.
citation: Mehta SR, Wood DA, Storey RF, Mehran R, Bainey KR, Nguyen H, Meeks B, Di Pasquale G, Lopez-Sendon J, Faxon DP, Mauri L, Rao SV, Feldman L, Steg PG, Avezum A, Sheth T, Pinilla-Echeverri N, Moreno R, Campo G, Wrigley B, Kedev S, Sutton A, Oliver R, Rodes-Cabau J, Stankovic G, Welsh R, Lavi S, Cantor WJ, Wang J, Nakamya J, Bangdiwala SI, Cairns JA; COMPLETE Trial Steering Committee and Investigators. Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med. 2019 Oct 10;381(15):1411-1421. doi: 10.1056/NEJMoa1907775. Epub 2019 Sep 1.
citation: Erlinge D, Maehara A, Ben-Yehuda O, Botker HE, Maeng M, Kjoller-Hansen L, Engstrom T, Matsumura M, Crowley A, Dressler O, Mintz GS, Frobert O, Persson J, Wiseth R, Larsen AI, Okkels Jensen L, Nordrehaug JE, Bleie O, Omerovic E, Held C, James SK, Ali ZA, Muller JE, Stone GW; PROSPECT II Investigators. Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study. Lancet. 2021 Mar 13;397(10278):985-995. doi: 10.1016/S0140-6736(21)00249-X.
citation: Stone GW, Maehara A, Ali ZA, Held C, Matsumura M, Kjoller-Hansen L, Botker HE, Maeng M, Engstrom T, Wiseth R, Persson J, Trovik T, Jensen U, James SK, Mintz GS, Dressler O, Crowley A, Ben-Yehuda O, Erlinge D; PROSPECT ABSORB Investigators. Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque. J Am Coll Cardiol. 2020 Nov 17;76(20):2289-2301. doi: 10.1016/j.jacc.2020.09.547. Epub 2020 Oct 15.
citation: Denormandie P, Simon T, Cayla G, Steg PG, Montalescot G, Durand-Zaleski I, le Bras A, le Breton H, Valy Y, Schiele F, Cuisset T, Vanzetto G, Levesque S, Goube P, Nallet O, Angoulvant D, Roubille F, Charles Nelson A, Chatellier G, Danchin N, Puymirat E. Compared Outcomes of ST-Segment-Elevation Myocardial Infarction Patients With Multivessel Disease Treated With Primary Percutaneous Coronary Intervention and Preserved Fractional Flow Reserve of Nonculprit Lesions Treated Conservatively and of Those With Low Fractional Flow Reserve Managed Invasively: Insights From the FLOWER-MI Trial. Circ Cardiovasc Interv. 2021 Nov;14(11):e011314. doi: 10.1161/CIRCINTERVENTIONS.121.011314. Epub 2021 Aug 23.