Functional Assessment of the Infart-related Artery With Bioactive and Polymer-free Coronary Stents (The FUNCOMBO Trial) (FUNCOMBO)

Six-month Endothelial and Microcirculatory Function of the Bioactive Sirolimus-eluting Combo Stent Versus the Polymer-free Biolimus-eluting Biofreedom Stent in Patients With ST-segment Elevation Myocardial Infarction

A total of 50 patients with ST-elevation myocardial infarction (STEMI) undergoing primary-percutaneous coronary intervention (PPCI) will be randomized to two different coronary stents: BIOFREEDOM vs. COMBO stent.

All patients will undergo to 6-month scheduled coronary angiography to evaluate the endothelial function response of the distal coronary segment and other functional parameters.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Endothelial Dysfunction; Coronary Microvascular Disease
• Intervention / Treatment: Procedure: Stent implantation in the infart-related artery in patients with ST elevation myocardial infarction

Detailed Description

The bioengineered COMBO stent (Orbus Neich, Fort Lauderdale, Florida, United States) has a dual-therapy strategy, which combines a sirolimus-eluting coating with an anti-CD34 antibody layer to promote vessel healing. Sirolimus release (5 μg/mm) is completed in 30 days, and the biodegradable polymer disappears within 90 days.

CD34 antibodies are immobilized on the surface of the stent and capture circulating endothelial progenitor cells (EPCs). The captured EPCs are triggered by sheer stress from the circulating blood and other cell signals to differentiate and mature into endothelial cells. COMBO Plus is the only stent with a biological coating that actively repairs the vessel morphology. However, little is known regarding the endothelial function after stent implantation.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • L'Hospitalet De Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• STEMI < 12 hours undergoing primary PCI.
• ST-segment elevation of > 1mm in > 2 contiguous leads, or (presumably new) left bundle branch block, or true posterior MI with ST depression of >1mm in >2 contiguous anterior leads.
• Presence of at least one acute infarct artery target vessel with one or more de-novo coronary artery stenosis in a native coronary artery within 2.75 - 3.75 mm reference vessel diameter and < 24 mm length (visually estimated).

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, PLLA, everolimus, contrast material
• Cardiogenic Shock
• Unprotected left main coronary artery stenosis
• Distal occlusion of target vessel
• Acute myocardial infarction secondary to stent thrombosis
• Mechanical complications of acute myocardial infarction
• Severe tortuous, calcified or angulated coronary anatomy of the study vessel that in the opinion of the investigator would result in sub-optimal imaging or excessive risk of complication in the follow-up procedure
• Active bleeding or coagulopathy or patients at chronic anticoagulation therapy
• Chronic renal dysfunction with creatinine clearance < 45 ml/minm2
• Subject is currently participating in another clinical trial that has not yet completed its primary endpoint

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BIOFREEDOM; Implantation of Drug-eluting coronary stent without polymer in patients with myocardial infarction.	Procedure: Stent implantation in the infart-related artery in patients with ST elevation myocardial infarction; The 6-month scheduled coronary angiography will perform 3 interventions: Endothelial function assessment with intracoronary acetyl-choline infusion.; Microcirculatory function assessment with a pressure wire during endovenous adenosine infusion.; Stent healing assessment using optical coherence tomography; Other Names: All patients will undergo to 6-month coronary angiography after stent implantation in order to assess the endothelial and microvascular function of the infarct related artery
Experimental: COMBO; Implantation of Bioactive coronary stent in patients with myocardial infarction.	Procedure: Stent implantation in the infart-related artery in patients with ST elevation myocardial infarction; The 6-month scheduled coronary angiography will perform 3 interventions: Endothelial function assessment with intracoronary acetyl-choline infusion.; Microcirculatory function assessment with a pressure wire during endovenous adenosine infusion.; Stent healing assessment using optical coherence tomography; Other Names: All patients will undergo to 6-month coronary angiography after stent implantation in order to assess the endothelial and microvascular function of the infarct related artery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial function of the distal coronary segment of patients with myocardial infarction treated with two types of drug-eluting stents	To compare the mean lumen diameter changes to intracoronary acetyl-choline infusion of the distal coronary segment by quantitative coronary angiography between the COMBO stent vs. the BIOFREEDOM stent in STEMI patients. Endothelial dysfunction is defined as >4% vasoconstriction to intracoronary acetylcholine compared to the 6-month baseline mean lumen diameter of the matched segment.	At 6 months of the stent implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Index of microcirculatory resistance	To compare the index of microcirculatory resistance (IMR) between the culprit arteries treated with COMBO vs. BIOFREEDOM in STEMI patients.	At 6 months of the stent implantation
Coronary flow reserve	To compare the coronary flow reserve (CFR) between the culprit arteries treated with COMBO vs. BIOFREEDOM in STEMI patients	At 6 months of the stent implantation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional flow reserve	To compare the fractional flow reserve (FFR) between the culprit arteries treated with COMBO vs. BIOFREEDOM in STEMI patients	At 6 months of the stent implantation

Collaborators and Investigators

• Sponsor: Institut d'Investigació Biomèdica de Bellvitge
• Collaborators: Spanish Society of Cardiology
• Investigators: Principal Investigator: Josep Gomez Lara, MD PhD, Hospital Universitari de Bellvitge, L´Hospitalet de Llobregat, Spain; Principal Investigator: Neus Salvatella, MD, Hospital del Mar, Barcelona, Spain; Principal Investigator: Salvatore Brugaletta, MD PhD, Hospital CLinic, Barcelona, Spain

Publications and helpful links

General Publications

• Gomez-Lara J, Oyarzabal L, Brugaletta S, Salvatella N, Romaguera R, Roura G, Fuentes L, Perez Fuentes P, Ortega-Paz L, Ferreiro JL, Teruel L, Gracida M, Vaquerizo B, Sabate M, Comin-Colet J, Gomez-Hospital JA. Coronary endothelial and microvascular function distal to polymer-free and endothelial cell-capturing drug-eluting stents. The randomized FUNCOMBO trial. Rev Esp Cardiol (Engl Ed). 2021 Dec;74(12):1013-1022. doi: 10.1016/j.rec.2021.01.007. Epub 2021 Feb 24. English, Spanish.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: October 28, 2018
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: endothelial function
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Angina Pectoris; Myocardial Infarction; Infarction; Microvascular Angina
• Other Study ID Numbers: AC009/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes