Treatment of Functionally Non-significant Vulnerable Plaques in Patients With Multivessel ST-elevation Myocardial Infarction The VULNERABLE Trial

Coronary Artery Disease Clinical Trial

— VULNERABLE  

Official title:

Treatment of Functionally Non-significant Vulnerable Plaques in Patients With Multivessel ST-elevation Myocardial Infarction The VULNERABLE Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05599061
• Other study ID #: EPIC28-VULNERABLE
• Status: Recruiting
• Phase: N/A
• Start date: January 30, 2023
• Est. completion date: December 1, 2028

Study information

• Verified date: June 2024
• Source: Fundación EPIC
• Contact: Josep Gomez-Lara, MD, PhD
• Phone: 0034677255399
• Email: gomezjosep[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 1, 2028
• Est. primary completion date: December 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Infarction
• Ischemic Heart Disease
• Myocardial Infarction
• Myocardial Ischemia
• ST Elevation Myocardial Infarction

Intervention

Other:
• FFR>0.80+ OCT with findings indicative of vulnerable plaque
Patients received OPTIMAL MEDICAL TREATMENT (OMT)+PCI
• FFR>0.80+ OCT with findings indicative of vulnerable plaque
OPTIMAL MEDICAL TREATMENT (OMT)

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Hospital General Universitario Dr.Balmis	Alicante
Spain	Hospital Universitari Sant Joan D'Alacant	Alicante
Spain	Hospital Universitari Germans Trias I Pujol	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de Santa Creu I Sant Pau	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitari Vall Hebron	Barcelona
Spain	Hospital Universitario Puerta Del Mar	Cadiz
Spain	Hospital General Universitario de Castellón	Castellón De La Plana
Spain	Hospital General Universitario de Ciudad Real	Ciudad Real
Spain	Hospital Universitario Reina Sofia de Cordoba	Córdoba
Spain	Hospital Universitario A Coruña	Coruña
Spain	Hospital General Universitario de Elche	Elche
Spain	Hospital Universitario de Cabueñes	Gijón
Spain	Hospital Universitario de Girona Dr Trueta	Girona
Spain	Hospital Universitario San Cecilio	Granada
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Juan Ramon Jimenez	Huelva
Spain	Hospital Universitario de Leon	León
Spain	Hospital La Princesa	Madrid
Spain	Hospital Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda
Spain	Hospital de Manises	Manises
Spain	Hospital Universitario Virgen Arrixaca	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Universitari Son Espases	Palma De Mallorca
Spain	Hospital Universitario de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario de Donostia	San Sebastián
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitari Joan Xxiii	Tarragona
Spain	Hospital Universitario Nuestra Señora de La Candelaria	Tenerife
Spain	Hospital Universitario de Torrevieja	Torrevieja
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitari I Politecnic La Fe	Valencia
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitari Miquel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Fundación EPIC	Abbott

Country where clinical trial is conducted

Spain, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Target Vessel Failure (TVF)	TVF as a composite of : Cardiovascular Death Target-vessel related MI Clinically and physiologically-oriented Target vessel revascularization	4 Years
Secondary	Cardiac death	To compare Cardiac death between both groups in the randomized arm death.	4 Years
Secondary	All-cause Death	To compare all death between both groups in the randomized arm death.	4 Years
Secondary	All Myocardial Infarctions	To compare Myocardial Infarctions between both groups in the randomized arm death. death	4 Years
Secondary	Target-Vessel Myocardial Infarction	To compare target-vessel myocardial infarction between both groups in the randomized arm.	4 Years
Secondary	Revascularizations	To compare all revascularizations between both groups in the randomized arm.	4 Years
Secondary	Ischemic-driven target vessel revascularization	To compare ischemic-driven target vessel revascularization between both groups in the randomized arm.	4 Years
Secondary	Patient-oriented endpoint of major adverse cardiac events	To compare the patient-oriented endpoint of major adverse cardiac events, a composite of all-cause death, myocardial infarction, and revascularization between both groups in the randomized arm.	4 Years
Secondary	Target Vessel Failure (TVF)	To compare the TVF rate between patients included in the OMT group of the randomized arm (presenting with vulnerable plaque) vs. patients included in the OMT registry (without vulnerable plaque).	4 Years
Secondary	Fractional Flow Reserve (FFR)	To compare the FFR values between patients with vulnerable plaques (randomized arm) and patients without vulnerable plaques (OMT registry).	4 years
Secondary	Minimal lumen area by Optical Coherence Tomography (OCT)	To establish the optimal OCT-derived minimal lumen area cutoff to predict an ischemic FFR in the non-culprit artery in the acute setting.	4 years
Secondary	Accuracy of vulnerable plaque assessment by Optical Coherence Tomography (OCT)	To compare the agreement between local operators and the core-laboratory to assess vulnerable plaques by OCT.	4 years