Randomized Trial Comparing Two Sirolimus-Eluting Stents in Diabetes Mellitus (INC-DM)

Randomized Trial Investigating Clinical Outcomes of Two Sirolimus-Eluting Stents in Diabetes Mellitus

Randomized, controlled, blind, single-center and non-inferiority clinical trial to compare the target lesion failure (TLF) at 12 months in patients with diabetes mellitus who underwent percutaneous coronary intervention with an Orsiro stent vs. Abluminus stent.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Diabetes Mellitus; Acute Coronary Syndrome
• Intervention / Treatment: Device: Abluminus Sirolimus Eluting Stent System (ASES); Device: Orsiro Sirolimus Eluting Coronary Stent System (OSES)

Detailed Description

Worldwide, and especially in Mexico, there is a high incidence of diabetes mellitus (DM), which in turn, confers a higher cardiovascular risk in this population. Diabetic patients undergoing PCI have worse outcomes than non-diabetics regardless of the degree of complexity of their coronary anatomy. Although the 30-day in-hospital outcomes have been similar between diabetic and non-diabetic patients, DM has been invariably associated with greater stent failure with target vessel revascularization (TVR), major adverse cardiovascular event (MACE), and mortality in the long-term follow-up, even with the use of drug-eluting stents. In relation to the above, two of the sirolimus-eluting stents (SES): the Abluminus and the Orsiro, have been considered as promising options in patients with DM. The Abluminus stent has been designed for diabetic patients in order to reduce cardiovascular events. Said stent consists of a cobalt-chromium platform covered with a layer of biodegradable polymer and mounted on a balloon, both sirolimus-releasing. The Rate of target lesion failure (TLF) reported to date in diabetic patients is 3.8%. On the other hand, the Orsiro stent, a cobalt-chromium platform with ultrathin struts, has had favorable results in different clinical settings and patients with different characteristics]; specifically in a subgroup analysis in DM, a TLF rate of 3.5% was reported

• Study Type: Interventional
• Enrollment (Estimated): 860
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alejandra D Portillo Romero, MD; Phone Number: 21217 +52 55 5573 2911; Email: aleportilloromero@gmail.com
• Study Contact Backup: Name: Guering Eid Lidt, MD; Phone Number: 21217 55 5573 2911; Email: guering@yahoo.com

Study Locations

• Mexico
  • Tlalpan
    • Mexico City, Tlalpan, Mexico, 14080
      • Recruiting
      • Instituto Nacional de Cardiología Ignacio Chavez
      • Contact: Alejandra D Portillo Romero, MD; Phone Number: 21217 +52 55 5573 2911; Email: aleportilloromero@gmail.com
      • Contact: Guering Edit Lid, MD; Phone Number: 21217 +52 55 5573 2911; Email: guering@yahoo.com
      • Principal Investigator: Guering Eid Lidt, MD
      • Principal Investigator: Julio I Farjat Pasos, MD MSc
      • Principal Investigator: Walter O Magaña Ornelas, MD
      • Principal Investigator: Alejandra D Portillo Romero, MD
      • Principal Investigator: José A Ayón Martinez, MD
      • Sub-Investigator: Maria E Soto López, MD PhD
      • Sub-Investigator: Iran Diaz Santillán, MD
      • Sub-Investigator: Gustavo Salinas Arteaga, MD
      • Sub-Investigator: Oscar Preciado, MD
      • Sub-Investigator: Jorge Gaspar, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women over 18 years of age.
• Provide informed consent and agree to follow up as stipulated in the protocol.

• Diabetes mellitus. Whether it is DM 1 or 2 previously diagnosed or newly diagnosed by:

  • Fasting glucose> 126 mg / dl (for study terms, fasting will be defined as the absence of caloric intake for> 8 hours)
  • Tolerance curve to glucose (75 grams of glucose orally) with a glycemia at 2 hours> 200 mg / dl or,
  • HbA1C> 6.5%.
• Coronary artery disease including chronic coronary syndrome, silent ischemia, or non-ST-segment elevation acute coronary ischemic syndrome.
• Presence of 1 or more de novo coronary lesions in native coronary arteries with a site of maximum stenosis> 50% that may be amenable to stenting; without limitation in the number of lesions or vessels affected.

Exclusion Criteria:

• Cardiogenic shock.
• Allergy to acetylsalicylic acid, clopidogrel, ticagrelor, prasugrel, heparin, sirolimus or contrast medium, which cannot be adequately premedicated.
• Acute ST-segment elevation myocardial infarction candidate for primary or urgent coronary angioplasty.
• Left main coronary artery disease.
• In-stent restenosis.
• Lesions in venous or arterial grafts.
• Surgery (cardiac or non-cardiac) planned within 6 months of PCI, unless dual antiplatelet therapy can be continued in the periprocedural period.
• Inability to provide informed consent.
• Life expectancy <1 year

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: Abluminus Sirolimus Eluting Stent System (ASES); The Abluminus sirolimus eluting stent manufactured by Envision and distributed by Concept Medical.	Device: Abluminus Sirolimus Eluting Stent System (ASES); The procedure will be conducted in accordance with the CE mark instructions for use for the ASES. The need or not for postdilation in any segment of the stent will be at the discretion of the operator, seeking its adequate expansion and apposition. To consider PCI to be successful, residual stenosis must be less than or equal to 30% by angiography at the end of the procedure, including the absence of coronary dissection that compromises distal flow or a hemodynamically significant pressure gradient across the lesion.
Experimental: Orsiro Sirolimus Eluting Coronary Stent System (OSES); The Orsiro sirolimus eluting stent manufactured by Biotronik.	Device: Orsiro Sirolimus Eluting Coronary Stent System (OSES); The procedure will be conducted in accordance with the CE mark instructions for use for the OSES. The need or not for postdilation in any segment of the stent will be at the discretion of the operator, seeking its adequate expansion and apposition. To consider PCI to be successful, residual stenosis must be less than or equal to 30% by angiography at the end of the procedure, including the absence of coronary dissection that compromises distal flow or a hemodynamically significant pressure gradient across the lesion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Target Lesion Failure (TLF)	To compare the rate of target lesion failure (composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target lesion revascularization)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Death	Cardiovascular death is defined as death resulting from cardiovascular causes. The following categories may be collected: Death caused by acute MI; Death caused by sudden cardiac, including unwitnessed, death; Death resulting from heart failure; Death caused by stroke; Death caused by cardiovascular procedures; Death resulting from cardiovascular hemorrhage; Death resulting from other cardiovascular causeAny MI not clearly attributable to a non-target vessel will be considered as target-vessel MI.Percutaneous coronary intervention (PCI) related MI is termed type 4a MI.Coronary artery bypass grafting (CABG) related MI is termed type 5 MI. Revascularization is clinically driven if the target lesion diameter stenosis is > 50% by quantitative coronary angiography (QCA) and the subject has clinical or functional ischemia which cannot be explained by another native coronary or bypass graft lesion.	12 months
Myocardial Infarction (MI)	Compare the myocardial infarction related to the treated vessel between both groups. (according to the 4th international definition of myocardial infarction) detection of an increase or decrease in cardiac troponin values with at least 1 of the values above the upper reference limit of the 99th percentile and at least 1 of the following conditions : Symptoms of acute myocardial ischemia.; New ischemic changes in the electrocardiogram.; Appearance of pathological Q waves.; Imaging evidence of loss of viable myocardium or new regional abnormalities in myocardial wall mobility following a pattern compatible with ischemic etiology.; Identification of a coronary thrombus by angiography with intracoronary imaging or by autopsyAny MI that cannot be clearly attributed to a vessel other than the revascularized one will be considered as MI related to the treated vessel.	12 months
Target Lesion Revascularization (TLR)	Revascularization is clinically driven if the target lesion diameter stenosis is > 50% by quantitative coronary angiography (QCA) and the subject has clinical or functional ischemia which cannot be explained by another native coronary or bypass graft lesion.	12 months
Target vessel revascularization (TVR)	TVR is a repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion.	12 months
Target vessel failure (TVF)	To compare the rate of target vessel failure (composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target vessel revascularization)	12 months
Death caused by other cardiovascular causes.	Compare death from any cause between the two groups. The following categories will be collected: Malignancy.; Pulmonary causes.; Infection.; Gastrointestinal causes.; Accident / trauma.; Caused by failure of another non-cardiovascular organ.; Other non-cardiovascular causes.Death that cannot be attributed to any of the aforementioned categories due to lack of information will be considered cardiovascular in terms of study outcomes.	12 months
Rate of in-stent restenosis (ISR)	Compare the rate of stent edge restenosis between both groups. Stenosis> 50% of the diameter and one or more of the following: symptoms suggestive of ischemia, electrocardiographic changes suggestive of ischemia, significant pressure gradient across the lesion; or a> 70% reduction in luminal area, even in the absence of data suggestive of ischemia. The categories will be collected according to the Waksman In-Stent Restenosis Classification: Type I: mechanicalIA UnderexpansionIIA Stent fracture; Type II: BiologicIIA Intimal hyperplasiaIIB Neoatherosclerosis, noncalcifiedIIC Neoatherosclerosis, calcified; Type III: Mixed pattern: Combined mechanical and biologic etiology; Type IV: Chronic total occlusion; Type V: >2 layers of stent	12 months
Rate of stent thrombosis (ST)	Compare the rate of stent thrombosis between both groups, According to the definition of the Academic Research Consortium (ARC) -2: Definitive thrombosis.; Probable thrombosis.; Silent occlusion.; Temporality: acute (0-24 hours), subacute (> 24 hours to 30 days), late (> 30 days to 1 year) and very late (> 1 year).	12 months
Major bleeding	Compare the incidence of bleeding complications according to The Bleeding Academic Research Consortium 2 (BARC-2) scale: 3 or greater.	12 months
Rate of Cerebrovascular Event	Compare the rate of cerebrovascular event between both groups according to Neuro-ARC stroke/ Transient ischemic attack (TIA) criteria.	12 months
Contrast Nephropathy	Creatinine increase >0.5 mg / dl or >25% over baseline at 48 hours after the procedure.	48 hours
Technical Success	Technical success is defined as the ability to cross the occluded segment with both a wire and a balloon, and successfully open the artery; the restoration of antegrade Thrombolysis In Myocardial Infarction (TIMI) flow 2 or 3 and a <30% residual stenosis.	12 months

Collaborators and Investigators

• Sponsor: Instituto Nacional de Cardiologia Ignacio Chavez
• Investigators: Study Director: Guering Eid Lidt, MD, Instituto Nacional de Cardiología Ignacio Chavez; Principal Investigator: Julio I Farjat Pasos, MD MSc, Instituto Nacional de Cardiología Ignacio Chavez; Principal Investigator: Walter O Magaña Ornelas, MD, Instituto Nacional de Cardiología Ignacio Chavez; Principal Investigator: Alejandra D Portillo Romero, MD, Instituto Nacional de Cardiología Ignacio Chavez; Principal Investigator: José A Ayón Martínez, MD, Instituto Nacional de Cardiología Ignacio Chavez

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 17, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Percutaneous coronary intervention; Orsiro; Albuminus
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Coronary Disease; Coronary Artery Disease; Diabetes Mellitus; Acute Coronary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus; Temsirolimus; MTOR Inhibitors
• Other Study ID Numbers: INCAR-DG-DI-342-2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No