• Demonstrate that PCI guided by iFR Co-registration is associated with superior clinical outcomes compared to PCI guided by angiography alone• To evaluate the cost-effectiveness of physiology guidance with SyncVision compared to a standard of care…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: Major Adverse Cardiac Events (MACE; composite of cardiac
death, MI, or ischemia-driven revascularization) or hospitalization for
progressive or unstable angina at 2 years
Not applicable for ChIL substudy - explanation as provided in the response
letter to RTPO:
There is no endpoint. The objective of the amendment is to only collect the
angiograms and invasive physiology measures that are part of a typical
diagnostic assessment for equivocal coronary artery lesions that are not
causing myocardial ischemia and hence do not get revascularized.
These data enable the development and validation of noninvasive tools that can
estimate the hemodynamic significance associated with a range of coronary
lesions.
The DEFINE GPS study is focused on comparing patient outcomes in those patients
that demonstrate the need for myocardial revascularization. The angiograms and
invasive physiology measures are being collected in these patients; however,
the prevalence of coronary artery disease that is indicated for
revascularization is only 30-35%; the need exists to collect data representing
the other 65-70% of the population that do not qualify for study inclusion.
Secondary outcome
Secondary endpoints (at 30 days, 1 year and 2 years if not noted otherwise):
• The primary endpoint at 30 days and 1 year
• All-cause, cardiac and non-cardiac mortality
• All MI, target vessel MI, non-target vessel MI, procedural MI, non-procedural
MI
• Ischemia-driven revascularization, including all revascularization, TVR, TLR,
non-TLR TVR, and non-TVR
• Hospitalization for progressive or unstable angina
• Stent thrombosis (definite, probable and definite/probable)
• Angina-related Quality of Life
• Healthcare resource utilization
• Cost effectiveness
Not applicable for ChIL substudy.
Background summary
Philips has developed a method to map the pressure profile of the locations and
severity of blockages in diseased blood vessels. This map is created on top of
a picture created by the x-ray. Patients will either get the normal *Angiogram
Alone* taken to guide their treatment, or they will get the *Angiogram with
Pressure Map.*
This study is being performed to determine if the treatment that uses the
Angiogram with Pressure Map results in greater relief of chest pain symptoms
and reduced heart complications for two years after treatment.
Background of the ChIL substudy:
DEFINE GPS enrolls patients that qualify to have at least one vessel
revascularized per criteria that are aligned with international guideline
recommendations for revascularization - including those intermediate lesions
demonstrating evidence of myocardial ischemia. A number of patients that are
consented for study participation are excluded from enrollment due to having
only angiographically present coronary stenoses in which the disease is not
hemodynamically significant. This sub-study is focused on collecting
additional imaging data on these intermediate vessels in patients that do not
have any hemodynamically significant lesion that qualifies them for
participation in DEFINE GPS.
Study objective
• Demonstrate that PCI guided by iFR Co-registration is associated with
superior clinical outcomes compared to PCI guided by angiography alone
• To evaluate the cost-effectiveness of physiology guidance with SyncVision
compared to a standard of care PCI strategy
• To establish the relationship between physiological guidance and improvement
in associated angina and quality of life scores
• To examine the outcomes in patients in whom an optimized post-PCI iFR can
versus cannot be achieved
Objective of the ChIL substudy:
• To collect baseline patient medical and demographic data along with
angiographic and functional data from vessels with intermediate disease
deferred from revascularization among those patients that are screen failures
for including in DEFINE GPS
• To establish a body of imaging data that can be used to validate new
image-based physiology applications
Study design
Multi-center, prospective, randomized controlled study employing an adaptive
design study for interim sample size re-estimation
Study design of the ChIL substudy:
Multi-center, prospective, registry study among patients that consent to be
randomized into the DEFINE GPS study but ultimately are not enrolled into the
study.
Intervention
The researchdoes not involve a new coronary intervention technique.
Not applicable for ChIL substudy.
Study burden and risks
Patients randomized to the physiology-guided arm will undergo multiple pressure
wire measurements that the patients in the angiograph-guided arm will not. Use
of any interventional device in the coronary arteries has an incidental risk
associated with it. The additional use of pressure wires in the
physiology-guided arm may place these patients at an incrementally higher risk
associated with the extra pressure wire procedures.
The Philips IGTD pressure guide wires used in this study are cleared for
commercial use by the FDA, CE marked for commercial distribution in Europe, or
otherwise appropriately registered for local use. Pressure guide wires are
intended for measuring pressure in the coronary vessels as described in this
protocol. Nothing about their use in this protocol is considered outside of
their intended use. Information related to contraindications, adverse effects,
warnings, and precautions are included in the device Instructions for Use.
For ChIL substudy:
The amount of radiation exposure patients will experience will be less than
those patients that qualify for the original study and require
revascularization. Patients may undergo radiation exposure that is equal to or
only minimally more than their baseline diagnostic coronary angiogram. The
risks associated with the additional exposure is within the same level of
stochastic risk as if they do not undergo any additional radiation. The
high-flow pressure measurement (*FFR*) is a Class IA recommendation for
assessing the significance of equivocal lesions to determine if a patient
should undergo myocardial revascularization. The overall risks are minimal and
the benefits are that the patient may undergo a more thorough diagnostic
assessment than they normally would. Finally, the data collected through this
effort may lead to tools that will minimize the need for a patient to undergo
the placement of invasive pressure wires in the future.
High Tech Campus 37
Eindhoven 5656AE
NL
High Tech Campus 37
Eindhoven 5656AE
NL
Listed location countries
Age
Inclusion criteria
1. Adult men and women (local age of consent) who present with stable or
unstable angina, or NSTEMI.
2. Undergoing cardiac catheterization with planned or possible ad hoc PCI
3. Following angiography, PCI is indicated in at least one coronary artery* on
the basis of one or more of the following:
a. Presenting with NSTE-ACS (unstable angina with ECG changes or cardiac
enzyme-positive NSTEMI) with an identified culprit lesion with DS >=50%;
b. One or more angiographic stenoses present with >=80% stenosis severity by
visual estimation;
c. One or more angiographic stenoses present with >=50% to <80% stenosis
severity by visual estimation and an abnormal non-invasive stress test in the
distribution of the lesion(s) within the past 60 days;
d. One or more angiographic stenoses are present with >=50% to <80% stenosis
severity by visual estimation and a spot iFR measure <=0.89.
Note: Multiple target vessels may be present. However, all must be qualified by
all inclusion and exclusion criteria prior to randomization, and all qualified
vessels must be treated per the randomization assignment (e.g. all with
standard angiographic guidance or all with physiologic guidance). Non-culprit
vessels in patients with NSTE-ACS must qualify by one of the criteria listed in
b-d above.
Staged procedures are permitted as detailed below.
4. Subject is willing to comply with all scheduled visits and tests and are
able and have provided informed written consent
*May or may not be known prior to consent. If patient is consented and
following angiography all inclusion criteria are not present or any exclusion
criteria are present, the patient will not be randomized
For the substudy ChIL:
1. Adult men and women (local age of consent) who present with stable angina
2. Undergoing cardiac catheterization with planned or possible ad hoc PCI
3. Following angiography, at least one epicardial vessel has one or more
angiographic stenoses with >=50% to <80% stenosis severity by visual estimation
and a spot iFR measure > 0.89 or FFR > 0.80.
4. Subject is willing to comply with all procedure steps and has provided
informed written consent
Exclusion criteria
1. STEMI within 30 days
2. PCI within the prior 12 months, or any PCI planned after the study procedure
(other than planned staged procedures of randomized vessels which are allowed)
3. Prior CABG anytime
4. Silent ischemia only (i.e. no cardiac symptoms related to coronary artery
disease) within the prior 4 weeks
5. Documented prior iFR pullback performed in any coronary artery including
during the qualifying diagnostic angiogram
6. Any vessel with in-stent restenosis (ISR) requiring treatment
7. Cardiogenic shock defined as systolic blood pressure <90 mmHg for >20
minutes not responding to fluid resuscitation, or need for inotropic, pressor,
or device-based hemodynamic support
8. Presence of unstable ventricular arrhythmias
9. Heart rate > 110, including uncontrolled atrial fibrillation (AF)
10. Decompensated congestive heart failure (NYHA Class IV or Killip Class III
or IV)
11. Chronic total occlusion (CTO) of a target vessel (exception: a CTO may be
present in a non-target vessel if it is supplying non-viable myocardium and
there is no intent to open the CTO during the index or later procedure)
12. Coronary anatomy not amenable to pressure wire manipulation due to extreme
tortuosity or complexity such that it is unlikely that a pressure wire could be
passed to the distal third of the three major epicardial coronary arteries
13. Any angiographic giant thrombus (i.e., thrombus length > 3x RVD at lesion)
14. Any target vessel with < TIMI III flow
15. Any target lesion with a reference vessel diameter (RVD) less than 2.25mm
except for within the side branch of a bifurcation lesion
16. Any non-target lesion with a reference vessel diameter (RVD) greater than
2.00mm that contains an >=80% stenosis and is not intended for treatment with PCI
17. Known severe aortic or mitral valve stenosis/insufficiency
18. Known non-cardiovascular comorbidity resulting in lifespan <24 months
19. Known left ventricular ejection fraction <=30%
20. Estimated creatinine clearance (MDRD formula) <30 mL/min/1.73m2 or on
dialysis
21. Any cardiac or non-cardiac surgical procedure planned within 12 months
after enrollment, or any procedure planned within 6 months after enrollment
that would necessitate discontinuation of dual antiplatelet therapy
22. Known pregnancy or planning to become pregnant (women of child-bearing
potential must have a negative pregnancy test within 1 week of enrollment)
23. Participating in another investigational drug or device study that has not
reached its primary endpoint
24. Any condition such as dementia or substance abuse that may impair the
patient*s ability to comply with all study procedures, including medication
compliance and follow-up visits
25. Patient is a member of a vulnerable population who, in the judgment of the
investigator, is unable to give Informed Consent for reasons of incapacity,
immaturity, adverse personal circumstances or lack of autonomy. This may
include individuals with mental disability, persons in nursing homes, children,
impoverished persons, persons in emergency situations, homeless persons,
nomads, refugees, and those permanently incapable of giving informed consent.
Vulnerable populations also include university students, subordinate hospital
and laboratory personnel, employees of the Sponsor, members of the armed
forces, and persons kept in detention.
For the ChIL Substudy:
Exclusion criteria from DEFINE GPS that are relevant for the ChIL sub-study
will apply and these are listed below. In addition, the ChIL sub-study has
additional specific target vessel angiographic exclusions which are listed
separately below.
From DEFINE GPS:
1. STEMI within 30 days
2. Prior CABG anytime
3. Cardiogenic shock defined as systolic blood pressure <90 mmHg for >20
minutes not responding to fluid resuscitation, or need for inotropic, pressor,
or device-based hemodynamic support
4. Presence of unstable ventricular arrhythmias
5. Heart rate > 110, including uncontrolled atrial fibrillation (AF)
6. Chronic total occlusion (CTO) of a target vessel (exception: a CTO may be
present in a non-target vessel if it is supplying non-viable myocardium and
there is no intent to open the CTO during the index or later procedure)
7. Coronary anatomy not amenable to pressure wire manipulation due to extreme
tortuosity or complexity such that it is unlikely that a pressure wire could be
passed to the distal third of the three major epicardial coronary arteries
8. Any angiographic giant thrombus (i.e., thrombus length > 3x RVD at lesion)
9. Any target vessel with < TIMI III flow
10. Any target lesion with a reference vessel diameter (RVD) less than 2.25mm
except for within the side branch of a bifurcation lesion
11. Known severe aortic or mitral valve stenosis/insufficiency
12. Known left ventricular ejection fraction <=30%
13. Estimated creatinine clearance (MDRD formula) <30 mL/min/1.73m2 or on
dialysis
14. Known pregnancy or planning to become pregnant (women of child-bearing
potential must have a negative pregnancy test within 1 week of enrollment)
15. Participating in another investigational drug or device study that has not
reached its primary endpoint
16. Any condition such as dementia or substance abuse that may impair the
patient*s ability to fully cooperate.
17. Patient is a member of a vulnerable population who, in the judgment of the
investigator, is unable to give Informed Consent for reasons of incapacity,
immaturity, adverse personal circumstances or lack of autonomy. This may
include individuals with mental disability, persons in nursing homes, children,
impoverished persons, persons in emergency situations, homeless persons,
nomads, refugees, and those permanently incapable of giving informed consent.
Vulnerable populations also include university students, subordinate hospital
and laboratory personnel, employees of the Sponsor, members of the armed
forces, and persons kept in detention.
ChIL Sub-study Target Vessel Exclusions:
1. Target vessel angiographic imaging having radiopaque interference associated
with prior cardiac implant (e.g., prior stent. artificial heart valve,
pacemaker)
2. Target vessel supplied by a left main coronary artery demonstrating any
disease present (isolated or non-isolated)
3. Target vessel supplied by right coronary artery demonstrating any ostial
disease (located immediately at the origin of the coronary vessels from the
aorta)
4. Target vessel with severe tortuosity (>=1 bends of 90° or more, or >=3 bends
of 45°- 90° proximal to the diseased segment)
5. Target vessel with heavy calcification (multiple persisting opacifications
of the coronary wall visible in more than one projection surrounding the
complete lumen of the coronary artery at the site of the lesion.)
6. Target vessel with severe diffuse disease (more than 75% of the length of
the segment having a vessel diameter of 2mm, irrespective of the presence or
absence of a lesion)
7. Target vessel supplied by major collaterals
8. Target vessel has vascular abnormality precluding optimal contrast
opacification (e,g, thrombus, ulceration)
9. Target vessel has an apparent muscle bridge
10. Target lesion is at a true bifurcation; i.e., Medina classification 1,0,0
or 0,1,0 or 0,0,1
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04451044 |
| CCMO | NL76491.099.21 |