A Randomized Multicentre Trial to Evaluate the Utilization of Revascularization or Optimal Medical Therapy for the Treatment of Chronic Total Coronary Occlusions (EuroCTO)

CTOs are common among patients with angina, and are detected in around 20% of patients undergoing coronary angiography. Treatment of CTO has been found to constitute only 7% of PCI practice on average. One of the reasons for the under-presentation of CTOs in PCI target lesions is the lack of evidence-based medical data on treatment indications, and the continued low level of accepted evidence for the treatment of CTOs by PCI in PCI guidelines.

Patients with a CTO represent patients with stable coronary artery disease. The COURAGE trial comparing PCI with optimal medical therapy in stable coronary disease did not show a difference in mortality or myocardial infarction between the two treatment options. However, CTOs were not included in the COURAGE trial. But that trial did confirm the superiority of PCI over OMT in controlling symptoms of angina, with a high cross-over rate to PCI. Whether PCI for CTO is superior to OMT in reducing MACE in those patients with a large ischaemic burden has never been tested in a randomized controlled trial.

While there is compelling evidence from registry studies of a clinical and prognostic benefit following successful PCI of CTO compared with PCI failure, there has been no randomized controlled trial of contemporary PCI using drug-eluting stents versus optimal medical therapy. The COURAGE trial nuclear sub-study confirms both that prognosis is closely related to the extent of residual ischaemia and that PCI is more effective in reducing residual ischaemia than optimal medical therapy alone. This confirms earlier retrospective data suggesting that the benefit of PCI is greatest in patients with moderate (10-20%) or severe (>20%) ischaemia.

Study hypothesis: PCI with Biolimus eluting stent implantation plus OMT will be superior to OMT alone in improving health status at 12-month follow-up, and will be noninferior with respect to the composite of all cause death/ non fatal MI at 36-month follow up, in patients with a CTO in an epicardial coronary artery >2.5 mm diameter and chronic stable angina with evidence of ischemia and viability in the territory subtended by the CTO

Study Overview

• Status: Completed
• Conditions: Coronary Occlusion; Dyspnea; Chronic Stable Angina
• Intervention / Treatment: Device: Biolimus-eluting stent implantation

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33074
    • Clinique Saint-Augustin
  • Lagny, France, 77405
    • CH de Lagny
  • Massy, France, 91300
    • Institut Hospitalier Jacques Cartier - ICPS
  • Toulouse, France, 31076
    • Clinique Pasteur
  • Toulouse, France, 31076
    • Rangueil University Hospital
• Germany
  • Bad Berka, Germany, 99438
    • Zentralklinik Bad Berka
  • Bad Krozingen, Germany, 79189
    • Herz-Zentrum Bad Krozingen
  • Bad Soden, Germany, 65812
    • Main Taunus Kliniken
  • Darmstadt, Germany, 64283
    • Klinikum Darmstadt
• Italy
  • Catania, Italy, 95126
    • Cardiac Catheterization Laboratory and Cardiovascular Interventional Unit Cannizzaro Hospita
• Latvia
  • Riga, Latvia, 1002
    • Latvian Center of Cardiology Pauls Stradins Clinical University Hospital
• Spain
  • Barcelona, Spain, 08025
    • Unidad de Cardiología Intervencionista Hospital de Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic Villaroel
  • Galdakao, Spain, 48960
    • Hospital Galdakao-Usansolo
  • Madrid, Spain, 28040
    • Cardiovascular Institute - Hospital Clinico San Carlos
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital - Brighton and Sussex University Hospitals
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Leicester, United Kingdom, LE3 9QP
    • Department of Cardiovascular Sciences University of Leicester
  • London, United Kingdom, SW7 2AZ
    • National Heart and Lung Institute Imperial College

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:

• ≥ 18 years of age with written informed consent
• CTO in native coronary artery
• a) Stable angina, or b) myocardial ischaemia in a territory supplied by CTO, and c) viability in akinetic myocardium (<50% transmural late enhancement on MRI or normal resting perfusion scan)
• CTO located in segments 1-3 (RCA), 6-7 (LAD), 11-12 (LCx)
• target artery ≥2.5mm

Exclusion Criteria:

• AMI or NSTE-ACS within 1 month
• Significant untreated coronary stenosis in a territory other than CTO
• Patients with MVD and significant non-CTO stenoses where it is deemed unsafe to treat the non-CTO lesion first (e.g. Significant proximal LAD lesion with chronically occluded RCA)
• Patient unsuitable for 12 month dual anti-platelet therapy
• Any exclusion criteria for PCI or DES
• Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following index procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Biolimus-eluting stent implantation; PCI of CTO using a Biomatrix drug-eluting stent system + optimal medical therapy.	Device: Biolimus-eluting stent implantation; Recanalization of chronic coronary artery occlusion and subsequent implantation of one or ore Biosensor stents; Other Names: Biosensors Biolimus-eluting stents of all sizes and lengths
NO_INTERVENTION: Medical therapy; Optimal medical therapy. Subsequent PCI only if symptoms of angina persist despite optimal medical therapy. At least 2 anti-anginal agents or the maximum tolerated anti-anginal therapy should be used before crossover. Medical therapy should include adequate ventricular rate-limiting medication (i.e. Beta-blocker or rate-limiting calcium antagonist) where appropriate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Seattle Angina Questionnaire (SAQ)	Seattle Angina Questionnaire and EQ-5D for health outcomes measurement	Baseline and 12 months
Major cardiovascular events	Cumulative composite endpoint of cardiovascular death, non-fatal MI at 3 years	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and efficacy endpoints	All cause mortality Cardiac mortality Myocardial Infarction Any hospitalization due to cardiovascular events (angina, congestive heart failure, arrythmias) Repeat revascularization	12 and 36 months
Procedural complications	Incl. periprocedural enzyme leak (defined by CK increase >3 times ULN); pericprocedural MI (new Q-wave or STEMI); pericardial tamponade, need for urgent CABG, CIN, death within 30 days, proven periprocedural cerebrovascular events	baseline upto 36 months
Protocol adherence	Need to cross from OMT to PCI in Group 2 (after escalation up to maximum tolerated anti-anginal therapy and persistent unequivocal symptoms)	36 months
Per protocol analysis	primary endpoint comparison in patients who did have a successful revascularization compared to those patients treated medically who had no subsequent PCI	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-economic analysis	Economic assessment & cost efficacy	12 and 36 months

Collaborators and Investigators

• Sponsor: Euro CTO Club
• Collaborators: NHS Research and Development; Biosensors International; Asahi Intecc Co., Ltd.
• Investigators: Principal Investigator: Gerald S Werner, MD PhD, Klinikum Darmstadt, Darmstadt Germany

Publications and helpful links

General Publications

• Werner GS, Martin-Yuste V, Hildick-Smith D, Boudou N, Sianos G, Gelev V, Rumoroso JR, Erglis A, Christiansen EH, Escaned J, di Mario C, Hovasse T, Teruel L, Bufe A, Lauer B, Bogaerts K, Goicolea J, Spratt JC, Gershlick AH, Galassi AR, Louvard Y; EUROCTO trial investigators. A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions. Eur Heart J. 2018 Jul 7;39(26):2484-2493. doi: 10.1093/eurheartj/ehy220.
• Azzalini L, Vo M, Dens J, Agostoni P. Myths to Debunk to Improve Management, Referral, and Outcomes in Patients With Chronic Total Occlusion of an Epicardial Coronary Artery. Am J Cardiol. 2015 Dec 1;116(11):1774-80. doi: 10.1016/j.amjcard.2015.08.050. Epub 2015 Sep 11.

Helpful Links

• Sponsor European CTO Club e.V. (ECC)

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2013
• Primary Completion (ACTUAL): May 1, 2016
• Study Completion (ACTUAL): November 1, 2018

Study Registration Dates

• First Submitted: January 1, 2013
• First Submitted That Met QC Criteria: January 1, 2013
• First Posted (ESTIMATE): January 3, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 29, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Pain; Neurologic Manifestations; Signs and Symptoms, Respiratory; Coronary Disease; Chest Pain; Angina Pectoris; Angina, Stable; Coronary Occlusion; Dyspnea
• Other Study ID Numbers: 2011-005905-64