Trial Evaluating New Strategy in the Functional Assessment of 3-vessel Disease Using SYNTAXII Score in Patients With PCI

• Sponsor: ECRI bv (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02015832
• Collaborator: Boston Scientific Corporation (Industry), Volcano Corporation (Industry)
• Enrollment: 454
• Locations: 22
• Actual Duration (Months): 83.9
• Patients Per Site: 20.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Clinical study that aims to evaluate a new strategy using the SYNTAX II Score calculator in the functional assessment of patients with new coronary 3-vessel-disease who undergo percutaneous coronary intervention (PCI)

Condition or Disease	Intervention/Treatment	Phase
Heart Diseases; Cardiovascular Diseases; 3 Vessel Coronary Artery Disease	Device: Coronary stent; Radiation: Multi Slice Computed Tomography; Device: instantaneous wave-free ratio; Device: Fractional flow reserve; Device: Intravascular Ultrasound

Detailed Description

The purpose of the SYNTAX II Trial is to investigate the management of de-novo 3-vessel-disease in order to prospectively assess which patients would have at least comparable short and long term clinical outcomes between coronary artery bypass graft and percutaneous coronary intervention (PCI), using contemporary PCI practice. In SYNTAX II the effectiveness of a contemporary stent (designed with thinner struts, biocompatible and biodegradable polymer, and a limus based drug), the use of pressure wire assessment of lesions to allow for ischemia-driven revascularisation, intravascular ultrasound (IVUS) guidance to optimise drug eluting stent deployment, and the treatment of (chronic) total occlusion lesions with contemporary techniques, will be compared against PCI practice in the original SYNTAX trial. The proposed study would involve the SYNTAX Score II to prospectively recruit subjects on the grounds of patient safety

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 454 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Single-arm Trial Evaluating the Effectiveness of PCI of de Novo 3-vessel Disease Applying the SYNTAX Score II With Pressure Wire Functional Assessment and IVUS Guidance, Using an Everolimus-eluting Stent With Biodegradable Abluminal Coating
• Actual Study Start Date: Feb 6, 2014
• Actual Primary Completion Date: Mar 28, 2017
• Actual Study Completion Date: Feb 4, 2021

Arms and Interventions

Arm

Intervention/Treatment

Percutaneous Coronary Intervention All patients (single arm study) will be receiving the SYNERGY™ Everolimus eluting stent (EES)

Device: Coronary stent; Other Names: SYNERGY™ EES ; Radiation: Multi Slice Computed Tomography; A coronary non-invasive Multi Slice Computed Tomography will be performed in patients; Other Names: MSCT ; Device: instantaneous wave-free ratio; Pressure-derived, adenosine-free index on physiological assessment of stenosis severity; Other Names: iFR ; Device: Fractional flow reserve; Pressure-derived index on physiological assessment of stenosis severity; Other Names: FFR ; Device: Intravascular Ultrasound; Allows the application of ultrasound technology to see from inside blood vessels out through the surrounding blood column, visualizing the inner wall of blood vessels; Other Names: IVUS

Outcome Measures

Primary Outcome Measures

1. Umber of Participants With Major Adverse Cardiac and Cerebrovascular Events (MACCE) [1 year]

   MACCE is defined as: all-cause death; cerebrovascular event (stroke); documented myocardial infarction or all-cause revascularization

Secondary Outcome Measures

1. Number of Participants With All-cause Death, Stroke, or Myocardial Infarction [1 Year]

   Safety endpoint

2. Number of Participants With All-cause Death [1 Year]

   All-cause death

3. Number of Participants With Stroke [1 Year]

   Stroke

4. Number of Participants With Myocardial Infarction [1 year]

   Any myocardial infarction

5. Number of Participants With Revascularization [1 Years]

   Any coronary revascularization

6. Number of Participants With Definite Stent Thrombosis [1 Year]

   Stent Thrombosis - according to ARC definitions. Definite ST can be confirmed with 1) angiography (the presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent and presence of at least 1 of the following criteria within a 48-hour time window: Acute onset of ischemic symptoms at rest; New ischemic ECG changes that suggest acute ischemia; Typical rise and fall in cardiac biomarkers (refer to definition of spontaneous MI); Non-occlusive thrombus or Occlusive thrombus; or 2) Pathological confirmation (evidence of recent thrombus within the stent determined at autopsy or via examination of tissue retrieved following thrombectomy).

7. Number of Participants With Probable Stent Thrombosis [1 year]

   Stent Thrombosis - according to ARC definitions. Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases: 1) Any unexplained death within the first 30 days; 2) Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 1 stenosis, angiographic, visually determined de novo lesions with more than 50 percent diameter stenosis in all 3 major epicardial territories. These are left descending coronary artery (LAD) and or side branch, proximal circumflex coronary artery (LCX) and or side branch, right descending coronary artery (RCA) and or side branch which are supplying viable myocardium without left main involvement. Patients with ostial LAD or ostial CX Medina 0,0,1 or Medina 0,1,0 may be enrolled

• Patients with hypoplastic RCA with absence of descending posterior and presence of a lesion in the LAD and CX territories may be included in the trial as a 3 vessel disease equivalent

• Vessel size should be at least 1.5 mm in diameter as visually assessed in diagnostic angiogram

• Patients with

1. stable (Canadian Cardiovascular Society Class 1, 2, 3 or 4) angina pectoris

2. or unstable (Braunwald class) angina pectoris and ischemia

3. or patients with atypical chest pain or those who are asymptomatic provided they have myocardial ischemia, for example treadmill exercise test, radionuclide scintigraphy, stress echocardiography

• All anatomical SYNTAX Scores are eligible for initial screening with the SYNTAX Score II

• Patient has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Ethical Committee of the respective clinical site

• Signed Heart Team Decision Form between local cardiologist and surgeon that the selected case meets all of the inclusion and exclusion criteria

Exclusion Criteria:

• Under the age of 21 years

• Known pregnancy at time of enrolment. Female of childbearing potential, and last menstruation within the last 12 months, who are not taking adequate contraceptives. Female who is breastfeeding at time of enrolment

• Prior PCI or CABG

• Ongoing acute myocardial infarction and enzymes (CKMB) more than 2x upper limit of normal

• Concomitant cardiac valve disease requiring surgical therapy, reconstruction or replacement

• Single or two-vessel disease at time of Heart Team consensus

• Participation or planned participation in another cardiovascular clinical study before one year follow up is completed

• Mental condition, psychiatric or organ cerebral disease, rendering the subject unable to understand the nature, scope, and possible consequences of the study or mental retardation or language barrier such that the patient is unable to give informed consent and potential for non-compliance towards the requirement in the study protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Center NL007	Amsterdam	Noord Holland	Netherlands
2	Research Center NL001	Rotterdam	Zuid-Holland	Netherlands
3	Research Center PL008	Bielsko-Biała		Poland
4	Research Center PL012	Katowice		Poland
5	Research Center PL010	Krakow		Poland
6	Research Center PL004	Poznan		Poland
7	Research Center ES009	Santander	Cantabria	Spain
8	Research Center ES001	Barcelona	Cataluna	Spain
9	Research Center ES007	Madrid	Comunidad Autonoma De Madrid	Spain
10	Research Center ES012	Madrid	Comunidad Autonoma De Madrid	Spain
11	Research Center ES015	Madrid	Comunidad Autonoma De Madrid	Spain
12	Research Center ES004	Vigo	Galicia	Spain
13	Research Center ES016	Salamanca		Spain
14	Research Center GB014	Belfast	County Antrim	United Kingdom
15	Research Center GB019	Oxford	Oxfordshire	United Kingdom
16	Research Center GB005	Brighton		United Kingdom
17	Research Center GB020	Cambridge		United Kingdom
18	Research Center GB015	Edinburgh		United Kingdom
19	Research Center GB001	Liverpool		United Kingdom
20	Research Center GB017	London		United Kingdom
21	Research Center GB006	Manchester		United Kingdom
22	Research Center GB013	Newcastle upon Tyne		United Kingdom

Sponsors and Collaborators

• ECRI bv
• Boston Scientific Corporation
• Volcano Corporation

Investigators

• Study Director: Ernest Spitzer, MD, European Cardiovascular Research Institute
• Principal Investigator: Javier Escaned, MD, Hospital San Carlos Madrid, Spain
• Principal Investigator: Adrian Banning, MD, John Radcliffe Hospital, Oxford, United Kingdom

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 27, 2013

More Information

Additional Information:

• 5-year final results of the SYNTAX II trial

Publications

None provided.

• Responsible Party: ECRI bv
• ClinicalTrials.gov Identifier: NCT02015832
• Other Study ID Numbers: ECRI-002
• First Posted: Dec 19, 2013
• Last Update Posted: Jul 21, 2022
• Last Verified: Jul 1, 2022

• Keywords provided by ECRI bv: SYNTAX II Score; Pressure wires; instantaneous wave-free ratio; fractional flow reserve; intravascular ultrasound; Drug eluting stents; Stents; Angioplasty; multi slice computed tomography
• Additional relevant MeSH terms: Cardiovascular Diseases; Coronary Artery Disease; Heart Diseases

Study Results

Participant Flow

Arm/Group Title	Percutaneous Coronary Intervention
Arm/Group Description	All-Comers, angiographic, de-novo 3-vessel disease without left main involvement (visual % diameter stenosis #50%).
Period Title: Overall Study
STARTED	454
COMPLETED	443
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Percutaneous Coronary Intervention
Arm/Group Description	All-Comers, angiographic, de-novo 3-vessel disease without left main involvement (visual % diameter stenosis #50%).
Overall Participants	454
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.7 (9.7)
Sex: Female, Male (Count of Participants)
Female	31 6.8%
Male	423 93.2%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Netherlands	36 7.9%
Poland	38 8.4%
United Kingdom	230 50.7%
Spain	150 33%

Outcome Measures

1. Primary Outcome

Title	Umber of Participants With Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Description	MACCE is defined as: all-cause death; cerebrovascular event (stroke); documented myocardial infarction or all-cause revascularization
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All patients enrolled in the SYNTAX II single-arm study were compared with a historical cohort selected from the SYNTAX I PCI arm (NCT00114972). Patients had three-vessel disease at presentation and qualified to enter the study based on equipoise to undergo either PCI or CABG according to the SYNTAX score II calculator (www.syntaxscore.org).

Arm/Group Title	SYNTAX II PCI Strategy Arm	Pre-defined SYNTAX I PCI Cohort
Arm/Group Description	Use of the SYNTAX II PCI strategy in patients with de novo three vessel disease. SYNTAX II PCI strategy included use of new generation DES, coronary physiology, and coronary imaging for stent implantation.	The historical comparator consisted on subjects enrolled in the SYNTAX I trial, treated with PCI, who would fulfill the SYNTAX II score criteria used in SYNTAX II (i.e. similar risk of undergoing PCI or CABG based on predicted mortality at 4 years).
Measure Participants	454	315
Count of Participants [Participants]	47 10.4%	54 NaN

2. Secondary Outcome

Title	Number of Participants With All-cause Death, Stroke, or Myocardial Infarction
Description	Safety endpoint
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

SYNTAX II PCI cohort vs. SYNTAX I PCI selected cohort.

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patient with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patient with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	17 3.7%	20 NaN

3. Secondary Outcome

Title	Number of Participants With All-cause Death
Description	All-cause death
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patients with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patients with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	9 2%	9 NaN

4. Secondary Outcome

Title	Number of Participants With Stroke
Description	Stroke
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patients with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patients with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	2 0.4%	2 NaN

5. Secondary Outcome

Title	Number of Participants With Myocardial Infarction
Description	Any myocardial infarction
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patients with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patients with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	6 1.3%	15 NaN

6. Secondary Outcome

Title	Number of Participants With Revascularization
Description	Any coronary revascularization
Time Frame	1 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patients with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patients with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	36 7.9%	42 NaN

7. Secondary Outcome

Title	Number of Participants With Definite Stent Thrombosis
Description	Stent Thrombosis - according to ARC definitions. Definite ST can be confirmed with 1) angiography (the presence of a thrombus that originates in the stent or in the segment 5 mm proximal or distal to the stent and presence of at least 1 of the following criteria within a 48-hour time window: Acute onset of ischemic symptoms at rest; New ischemic ECG changes that suggest acute ischemia; Typical rise and fall in cardiac biomarkers (refer to definition of spontaneous MI); Non-occlusive thrombus or Occlusive thrombus; or 2) Pathological confirmation (evidence of recent thrombus within the stent determined at autopsy or via examination of tissue retrieved following thrombectomy).
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patients with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patients with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	3 0.7%	8 NaN

8. Secondary Outcome

Title	Number of Participants With Probable Stent Thrombosis
Description	Stent Thrombosis - according to ARC definitions. Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases: 1) Any unexplained death within the first 30 days; 2) Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SYNTAX II PCI Cohort	SYNTAX I PCI Cohort
Arm/Group Description	Patients with de-novo three vessel disease undergoing PCI according to the SYNTAX II strategy, including coronary physiology, imaging, and new generation drug-eluting stents.	Patients with de-novo three vessel disease undergoing PCI according in the SYNTAX I trial, who would qualify as comparators for SYNTAX II based on equipoise between CABG and PCI using the SYNTAX score II calculator (www.syntaxscore.org).
Measure Participants	454	315
Count of Participants [Participants]	1 0.2%	0 NaN

Adverse Events

Time Frame	5 years
Arm/Group Title	Percutaneous Coronary Intervention
Arm/Group Description	All-Comers, angiographic, de-novo 3-vessel disease without left main involvement (visual % diameter stenosis #50%).
All Cause Mortality
	Percutaneous Coronary Intervention
	Affected / at Risk (%)	# Events
Total	36/454 (7.9%)
Serious Adverse Events
	Percutaneous Coronary Intervention
	Affected / at Risk (%)	# Events
Total	125/454 (27.5%)
Cardiac disorders
Myocardial Infarction	12/454 (2.6%)	125
All-cause Revascularization	60/454 (13.2%)	125
Stroke	10/454 (2.2%)	125
Stent Thrombosis	7/454 (1.5%)	125
General disorders
Death	36/454 (7.9%)	125
Other (Not Including Serious) Adverse Events
	Percutaneous Coronary Intervention
	Affected / at Risk (%)	# Events
Total	0/454 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.