Coronary Artery DiseaseVERIFY2NCT02377310
Pd/Pa vs iFR™ in an Unselected Population Referred for Invasive Angiography
An observational study of Coronary Artery Disease and Plaque, run by Golden Jubilee National Hospital at 1 site in United Kingdom.
Trial summary
Instantaneous wave-free ratio (iFR™) is a novel non-hyperaemic index of the functional significance of a coronary stenosis. Previous studies have shown variable levels of correlation with the established hyperaemic index FFR. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Plaque, Atherosclerosis
- How many people
- 197 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2013to Apr 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All consecutive patients undergoing FFR assessment for standard clinical indications.
Who may be able to join
- All patients ≥18 years of age, already undergoing pressure wire assessment and able to consent
Who cannot join
- Inability to receive adenosine
- Extremely tortuous vessels
- Highly calcified lesions unsuitable for pressure wire assessment
- coronary artery occlusion
- acute MI within 3 days
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Golden Jubilee National Hospital
Glasgow, Dunbartonshire, G81 4DY
About this study
Official title: A Comparative Study of Resting Coronary Pressure Gradient, Instantaneous Wave-free Ratio and Fractional Flow Reserve in an Unselected Population Referred for Invasive Angiography: The VERIFY 2 Study
Instantaneous wave-free ratio (iFR™) is a novel non-hyperaemic index of the functional significance of a coronary stenosis. Previous studies have shown variable levels of correlation with the established hyperaemic index FFR. In addition it has been proposed that iFR™ has superior diagnostic accuracy when compared to mean whole cardiac cycle Pd/Pa which can also be used to predict FFR.
We plan to undertake a prospective clinical study in consecutive patients already undergoing FFR assessment in the cardiac catheterisation laboratory to compare the ability of iFR™ and Pd/Pa (both measured using the proprietary Volcano system) to predict FFR. We will explore the level of misclassification of flow limiting disease that results from use of iFR™ and resting Pd/Pa employed using either binary cut-off algorithms or in a hybrid decision making protocol. We plan to analyse 260 vessels over a 18 month period. Hyperaemia will be induced by intravenous adenosine (140 ug/kg/min) administered wherever possible via an antecubital vein. Intra-coronary nitrates will also be given in line with the standard care procedure for FFR measurement. Final clinical decisions following coronary physiology will be based on steady state FFR.
Read the detailed description
Title:
A comparative study of resting Pd/Pa, instantaneous wave-free ratio and fractional flow reserve in an unselected population referred for invasive angiography.
Instantaneous wave-free ratio (iFR™) is a novel non-hyperaemic index for assessing the functional significance of a coronary stenosis without coronary vasodilatation. In previous studies it has been compared to the hyperaemic index FFR with variable results. As a guide to determining the need for revascularisation it has been employed using a dichotomous cut-off without FFR or within a hybrid strategy in which lesions with intermediate iFR™ values are further interrogated using FFR.
The comparative diagnostic utility of iFR™ vs resting pressure (Pd/Pa) in reference to FFR is uncertain. We plan to undertake a prospective clinical study in consecutive patients undergoing clinically-indicated FFR assessment in the cardiac catheterisation laboratory with 30-80% diameter stenosis on quantitative coronary angiography (QCA). We will will use a proprietary (Volcano) pressure wire system and iFR ™ algorithm in order to calculate iFR™ and Pd/Pa in both resting and hyperemic conditions as well as FFR.
The sample size is 260 vessels and the enrolment period is 18 months. Hyperaemia will be induced by intravenous adenosine (140 ug/kg/min) administered wherever possible via an antecubital vein. Intra-coronary nitrates will also be given in line with the standard care procedure for FFR measurement.
Design:
In this prospective single centre cohort study all consecutive patients undergoing FFR are eligible for inclusion.
Active Hypothesis: (1) In comparison to an FFR for all strategy, revascularisation decisions made using binary cut-off values of iFR™ or resting Pd/Pa will result in similar levels of disagreement.
Active Hypothesis: (2) In comparison to an FFR for all strategy, revascularisation decisions using hybrid strategies incorporating iFR™ or resting Pd/Pa and FFR will result in similar levels of disagreement.
Active Hypothesis (3): Compared to iFR™ measured under resting conditions, hyperaemic iFR™ has a stronger correlation with FFR. Should this be the case, then the diagnostic efficiency of iFR™ can be interpreted as being improved with pharmacological vasodilatation. The null hypothesis is that there is no difference in diagnostic efficiency between iFR™ and hyperaemic iFR compared to FFR.
The clinical decisions in the catheter laboratory will align with routine care and be informed by all available clinical data and the FFR results.
This study is being conducted independently in the National Health Service without industry support or involvement.
Sample size: 260 vessels.
Statistical Analysis: Independent analysis of the completed dataset will be performed by Dr John McClure a biostatistician and lecturer in the Institute of Cardiovascular and Medical Sciences in Glasgow.
Methods: We will measure resting indices Pd/Pa and iFR™. Following this we will then measure hyperaemic readings including FFR and hyperaemic iFR™ (HiFR) sequentially using peripherally administered adenosine. Upon completion of enrollment we will produce summary statistics describing demographics and procedural data for the study cases. We will then calculate the discriminatory power of iFR™ using both the pre-specified binary cut-off values of 0.90 for iFR™ and 0.92 for resting Pd/Pa and the adenosine zones for iFR of 0.86-0.93 and resting Pd/Pa of 0.87-0.94. We will also analyse the correlation of HiFR with FFR
- Medical subject headings
- Coronary Artery Disease, Plaque, Amyloid, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| All patients | All patients will undergo coronary physiological study with measurement of resting Pd/Pa, iFR™, hyperaemic iFR and FFR. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the diagnostic accuracy of instantaneous wave-free ratio (binary cut-off value 0.90) versus resting Pd/Pa (binary cut-off value 0.92) in reference to FFR.
Resting Pd/Pa will be compared to iFR™ in reference to FFR.
Measured: 30 days
Secondary outcomes (5)
To determine the diagnostic accuracy of hybrid iFR™/FFR versus hybrid resting Pd/Pa/FFR in reference to FFR
Adenosine zone for iFR is 0.86-0.93, Adenosine zone for resting Pd/Pa is 0.87-0.94.
Measured: 30 days
To compare steady state FFR to minimum FFR
FFR recorded by the operator as the minimum value will be compared with the steady state value and the impact on vessel classification will be assessed
Measured: 30 days
To investigate the influence of hyperemia on iFR™.
iFR™ will be reassessed after administration of adenosine to evaluate whether this increases agreement with FFR.
Measured: 30 days
To assess the rate of revascularization per (1) artery and (2) per patient, associated with iFR™-guided management vs. FFR-guided management.
An analysis of the total number of vessels and patients that would potentially undergo revascularisation will be used to compare iFR™ versus FFR guided managment.
Measured: 30 days
To assess serious adverse events in patients receiving intravenous adenosine
Patients will be monitored during coronary physiology studies to assess the safety of intravenous adenosine infusion with assessment of side effects leading to early termination of the infusion.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study startSep 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- Golden Jubilee National Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Keith G Oldroyd, M.D., Study director, Golden Jubilee National Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02377310
- Sponsor's protocol ID
- 1.0
- Acronym
- VERIFY2
- Status last verified
- Aug 2015
- First submitted
- 26 Feb 2015
- Last updated
- 13 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC; Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Clin Radiol. 2003 Aug;58(8):575-80. doi: 10.1016/s0009-9260(03)00258-7.
PubMed 12887949Van't Veer M, Pijls NHJ, Hennigan B, Watkins S, Ali ZA, De Bruyne B, Zimmermann FM, van Nunen LX, Barbato E, Berry C, Oldroyd KG. Comparison of Different Diastolic Resting Indexes to iFR: Are They All Equal? J Am Coll Cardiol. 2017 Dec 26;70(25):3088-3096. doi: 10.1016/j.jacc.2017.10.066.
PubMed 29268922Hennigan B, Oldroyd KG, Berry C, Johnson N, McClure J, McCartney P, McEntegart MB, Eteiba H, Petrie MC, Rocchiccioli P, Good R, Lindsay MM, Hood S, Watkins S. Discordance Between Resting and Hyperemic Indices of Coronary Stenosis Severity: The VERIFY 2 Study (A Comparative Study of Resting Coronary Pressure Gradient, Instantaneous Wave-Free Ratio and Fractional Flow Reserve in an Unselected Population Referred for Invasive Angiography). Circ Cardiovasc Interv. 2016 Nov;9(11):e004016. doi: 10.1161/CIRCINTERVENTIONS.116.004016.
PubMed 27834663
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparative Study of Resting Coronary Pressure Gradient, Instantaneous Wave-free Ratio and Fractional Flow Reserve in an Unselected Population Referred for Invasive Angiography: The VERIFY 2 Study
- ClinicalTrials.gov ID
- NCT02377310
- Acronym / sponsor ID
- VERIFY2 / 1.0
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- Golden Jubilee National HospitalOther government
- Study start
- Sep 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Instantaneous wave-free ratio (iFR™) is a novel non-hyperaemic index of the functional significance of a coronary stenosis. Previous studies have shown variable levels of correlation with the established hyperaemic index FFR. In addition it has been proposed that iFR™ has superior diagnostic accuracy when compared to mean whole cardiac cycle Pd/Pa which can also be used to predict FFR.
We plan to undertake a prospective clinical study in consecutive patients already undergoing FFR assessment in the cardiac catheterisation laboratory to compare the ability of iFR™ and Pd/Pa (both measured using the proprietary Volcano system) to predict FFR. We will explore the level of misclassification of flow limiting disease that results from use of iFR™ and resting Pd/Pa employed using either binary cut-off algorithms or in a hybrid decision making protocol. We plan to analyse 260 vessels over a 18 month period. Hyperaemia will be induced by intravenous adenosine (140 ug/kg/min) administered wherever possible via an antecubital vein. Intra-coronary nitrates will also be given in line with the standard care procedure for FFR measurement. Final clinical decisions following coronary physiology will be based on steady state FFR.
Detailed description
Title:
A comparative study of resting Pd/Pa, instantaneous wave-free ratio and fractional flow reserve in an unselected population referred for invasive angiography.
Instantaneous wave-free ratio (iFR™) is a novel non-hyperaemic index for assessing the functional significance of a coronary stenosis without coronary vasodilatation. In previous studies it has been compared to the hyperaemic index FFR with variable results. As a guide to determining the need for revascularisation it has been employed using a dichotomous cut-off without FFR or within a hybrid strategy in which lesions with intermediate iFR™ values are further interrogated using FFR.
The comparative diagnostic utility of iFR™ vs resting pressure (Pd/Pa) in reference to FFR is uncertain. We plan to undertake a prospective clinical study in consecutive patients undergoing clinically-indicated FFR assessment in the cardiac catheterisation laboratory with 30-80% diameter stenosis on quantitative coronary angiography (QCA). We will will use a proprietary (Volcano) pressure wire system and iFR ™ algorithm in order to calculate iFR™ and Pd/Pa in both resting and hyperemic conditions as well as FFR.
The sample size is 260 vessels and the enrolment period is 18 months. Hyperaemia will be induced by intravenous adenosine (140 ug/kg/min) administered wherever possible via an antecubital vein. Intra-coronary nitrates will also be given in line with the standard care procedure for FFR measurement.
Design:
In this prospective single centre cohort study all consecutive patients undergoing FFR are eligible for inclusion.
Active Hypothesis: (1) In comparison to an FFR for all strategy, revascularisation decisions made using binary cut-off values of iFR™ or resting Pd/Pa will result in similar levels of disagreement.
Active Hypothesis: (2) In comparison to an FFR for all strategy, revascularisation decisions using hybrid strategies incorporating iFR™ or resting Pd/Pa and FFR will result in similar levels of disagreement.
Active Hypothesis (3): Compared to iFR™ measured under resting conditions, hyperaemic iFR™ has a stronger correlation with FFR. Should this be the case, then the diagnostic efficiency of iFR™ can be interpreted as being improved with pharmacological vasodilatation. The null hypothesis is that there is no difference in diagnostic efficiency between iFR™ and hyperaemic iFR compared to FFR.
The clinical decisions in the catheter laboratory will align with routine care and be informed by all available clinical data and the FFR results.
This study is being conducted independently in the National Health Service without industry support or involvement.
Sample size: 260 vessels.
Statistical Analysis: Independent analysis of the completed dataset will be performed by Dr John McClure a biostatistician and lecturer in the Institute of Cardiovascular and Medical Sciences in Glasgow.
Methods: We will measure resting indices Pd/Pa and iFR™. Following this we will then measure hyperaemic readings including FFR and hyperaemic iFR™ (HiFR) sequentially using peripherally administered adenosine. Upon completion of enrollment we will produce summary statistics describing demographics and procedural data for the study cases. We will then calculate the discriminatory power of iFR™ using both the pre-specified binary cut-off values of 0.90 for iFR™ and 0.92 for resting Pd/Pa and the adenosine zones for iFR of 0.86-0.93 and resting Pd/Pa of 0.87-0.94. We will also analyse the correlation of HiFR with FFR
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | – | –All patients will undergo coronary physiological study with measurement of resting Pd/Pa, iFR™, hyperaemic iFR and FFR. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All consecutive patients undergoing FFR assessment for standard clinical indications.
Key inclusion criteria (1 listed)
- All patients ≥18 years of age, already undergoing pressure wire assessment and able to consent
Key exclusion criteria (5 listed)
- Inability to receive adenosine
- Extremely tortuous vessels
- Highly calcified lesions unsuitable for pressure wire assessment
- coronary artery occlusion
- acute MI within 3 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To determine the diagnostic accuracy of instantaneous wave-free ratio (binary cut-off value 0.90) versus resting Pd/Pa (binary cut-off value 0.92) in reference to FFR.
Time frame: 30 days
Resting Pd/Pa will be compared to iFR™ in reference to FFR.
5 secondary outcomes
To determine the diagnostic accuracy of hybrid iFR™/FFR versus hybrid resting Pd/Pa/FFR in reference to FFR
Time frame: 30 days
To compare steady state FFR to minimum FFR
Time frame: 30 days
To investigate the influence of hyperemia on iFR™.
Time frame: 30 days
To assess the rate of revascularization per (1) artery and (2) per patient, associated with iFR™-guided management vs. FFR-guided management.
Time frame: 30 days
To assess serious adverse events in patients receiving intravenous adenosine
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
- Background: PubMed 12887949Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC; Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Clin Radiol. 2003 Aug;58(8):575-80. doi: 10.1016/s0009-9260(03)00258-7.
- Derived from this study: PubMed 29268922Van't Veer M, Pijls NHJ, Hennigan B, Watkins S, Ali ZA, De Bruyne B, Zimmermann FM, van Nunen LX, Barbato E, Berry C, Oldroyd KG. Comparison of Different Diastolic Resting Indexes to iFR: Are They All Equal? J Am Coll Cardiol. 2017 Dec 26;70(25):3088-3096. doi: 10.1016/j.jacc.2017.10.066.
- Derived from this study: PubMed 27834663Hennigan B, Oldroyd KG, Berry C, Johnson N, McClure J, McCartney P, McEntegart MB, Eteiba H, Petrie MC, Rocchiccioli P, Good R, Lindsay MM, Hood S, Watkins S. Discordance Between Resting and Hyperemic Indices of Coronary Stenosis Severity: The VERIFY 2 Study (A Comparative Study of Resting Coronary Pressure Gradient, Instantaneous Wave-Free Ratio and Fractional Flow Reserve in an Unselected Population Referred for Invasive Angiography). Circ Cardiovasc Interv. 2016 Nov;9(11):e004016. doi: 10.1161/CIRCINTERVENTIONS.116.004016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith G Oldroyd, M.D. study director
Golden Jubilee National Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Artery Disease and Plaque, run by Golden Jubilee National Hospital at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the diagnostic accuracy of instantaneous wave-free ratio (binary cut-off value 0.90) versus resting Pd/Pa (binary cut-off value 0.92) in reference to FFR. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02377310, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2015.