Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05658952 |
| Other study ID # |
828/2022/DispAOUFe |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2022 |
| Est. completion date |
June 20, 2024 |
Study information
| Verified date |
June 2023 |
| Source |
University Hospital of Ferrara |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Angiography-derived Fractional Flow Reserve (FFR) Virtual Percutaneous Coronary Intervention
(PCI) plan is superior to conventional angiography-guided PCI in obtaining a good final
physiology result, which is, in turn, associated with better prognosis. This has been
demonstrated in a population with a relatively low lesion complexity.
Therefore, whether angiography-based FFR virtual PCI could guarantee the same results in some
complex anatomical settings (tortuous or calcific vessels, tandem or bifurcation lesions) is
not known, also given the inherent limitations of the 3Dimensional (3D)-reconstruction.
The ability of invasive FFR to achieve the same result if compared to angiography-guided PCI
has been questioned by recent studies. Recent technological developments, namely the design
of pressure wire microcatheters may allow an easier handling of the procedural planning and
guidance.
The rationale of the AQVA II study is to test whether a longitudinal FFR-based virtual PCI
either angio- or microcatheter- derived is able to improve the post-PCI physiology value if
compared to angio-guided PCI in complex and high-risk indicated procedures (CHIP).
Description:
Despite the accumulating evidence regarding functional indices utility in setting the
indication to and planning percutaneous coronary interventions (PCI), the use of functional
assessment in clinical practice is still limited. This is especially true in the post-PCI
setting, probably due to lack of evidence and/or specific guidelines/recommendations on how
to "react" to a suboptimal post-PCI functional result.
New indices and tools have been developed in an effort to overcome the barriers to a
widespread adoption of functional assessment.
All these technological advances brought physiology to a new level transitioning from a
binary interpretation of the functional evaluation - positive or negative - to a longitudinal
analysis of the whole vessel. The reconstruction of a "physiological map" enables to quantify
the physiological impact of each coronary segment/lesion and to identify the mechanisms
underlying the suboptimal physiology result at the vessel level. This ability can be
translated in simple manoeuvres able to improve the final physiology results and then the
patient's prognosis.
The inherent limit of post-PCI physiology is to add measurement and consequent actions after
the end of the procedure and not upfront. In addition, it is associated with the increase in
procedural time and costs. Thus, a broad application of post-PCI physiology, although
clinically meaningful, is difficult.
On the contrary, the systematic application of angiography-derived FFR before stenting to
simulate PCI results according to different treatment strategies (virtual PCI) would be an
interesting alternative to achieve a fully physiology-guided and optimized procedure. The
powerful technological development lays in the possibility to simulate the treatment of one
or more lesion, in order to estimate the residual functional value post-PCI: the so-called
virtual PCI. These tools are particularly effective in multi-vessel disease patients and in
tandem serial stenosis, allowing to individualize the treatment of those lesions related to
poor clinical outcomes and avoiding superfluous coronary interventions.
The advantages of a virtual PCI strategy based on angiography-derived FFR application are:
- simple tool, based on what the operator already performs before PCI (namely one or two
perpendicular angiographic projections) and not requiring wire or adenosine;
- enables to obtain a longitudinal physiologic map of the vessel with a point-by-point
detailed information of the individual impact of any given stenosis;
- simulate the treatment of one or more lesions (virtual PCI) in order to estimate the
final functional value post-PCI.
The "Angio-based Quantitative flow ratio (QFR) Virtual PCI versus Conventional Angio-guided
PCI in the achievement of an optimal post-PCI QFR" (AQVA)-I trial was the first step toward
this direction. The AQVA was a multicenter, investigator-driven, randomized, controlled,
parallel group clinical trial. Patients with evidence of angiographically critical coronary
lesions and indication to PCI were randomized 1:1 to either angiography-derived FFR virtual
PCI or conventional angiography-based PCI. The study aimed to demonstrate the superiority of
the angiography-derived FFR virtual PCI over the angiography-based PCI at obtaining an
optimal post-PCI result (as defined as a post-PCI QFR value ≥0.90).
From February to December 2021, 300 patients met all inclusion and exclusion criteria and
were randomized, for a total of 356 study vessels.
Overall, 38 (10.7%) vessels missed the prespecified post-PCI angiography-derived FFR target
(≥0.90). The primary outcome occurred significantly more frequently in the angio-based PCI
group (n=26, 15.1%) when compared with the virtual PCI group (n=12, 6.6%; absolute difference
8.5%, relative difference 57%, confidence interval 2.2% - 15.0%, p=0.009). The Δ between pre-
and post-PCI physiology value was higher in the virtual PCI groups if compared to the
angiography-based group with borderline statistical significance (0.29 [0.23-0.37] versus
0.27 [0.20-0.36], p=0.05).
There were no significant differences among procedural secondary endpoints, such as
procedural duration, contrast dye and x-ray utilization. Stent length/lesion and stent
number/patient were numerically lower in the virtual PCI group (1 [1-2]; 1.4±0.6 vs 1 [1-2]
1.6±0.7, p=0.06 and 40 [25-55]; 42.7±20.1 vs 44 [28-60]; 46.1±23.1, p=0.08, respectively)
whereas procedure length was numerically higher in the virtual PCI group (66 [51-82]; 69±23.1
vs 67 [57-88]; 73.9±23.9, p=0.06). Therefore, virtual PCI based on angiography-derived FFR
represents the actual standard of care to guarantee an optimal result in terms of physiology.
The present AQVA-II trial represents the next step of the same approach towards more complex
lesions settings.
Patients with severe coronary artery disease at high procedural risk because of
comorbidities, complexity of coronary anatomy, and/or poor hemodynamic represent an
understudied and underserved patient population.
One of the main limitations of the AQVA-I trial is the absence of a strict inclusion criteria
regarding complex and high risk indicated procedures (CHIP)-like lesions (5). The only
suggestion was to include long lesions (> 20 mm). Even though, 64 (18%) of included lesions
were < 20 mm partially diluting the advantage of the tested strategy. This is confirmed by
the high median post-PCI QFR value in both groups (0.97 [0.94-1]). In the study group, namely
patients undergoing virtual PCI, the degree of lesions complexity was overall low. The
relative simplicity of the lesions included in the AQVA-I trial raises doubts about the
validity of the results in contexts of greater complexity, where optimal PCI planning and
tools might be different.
Different rapid exchange microcatheters have been developed for FFR assessment.
Microcatheters have an ultra-thin profile and they have been designed to allow a rapid
exchange system on work-horse wire and easy handling of complex lesions.
As compared to wire-based FFR systems, the potential main advantages of microcatheter-based
FFR are:
- Advancement over any traditional 0.014" coronary guidewire;
- The position of the work-horse wire can be maintained during all the procedure, even
during pullbacks and post-PCI assessment;
- Tortuous vessels, ostial and/or challenging lesions can be crossed with the work-horse
wire and investigated without the need of additional wiring;
- No need for disconnection and reconnection of cable during procedures;
- Less occurrence of clinically significant drift (due to the incorporation of an optical
pressure sensor).
To sum up, FFR microcatheter enables to carry out functional evaluations in complex anatomies
scenarios (tortuous or calcific vessels, tandem or bifurcation lesions).
At the moment, while microcatheter FFR can be a game changer in vessels with tortuosity, in
long challenging diseases, in ostial lesions, and in patients with several comorbidities,
there is no clear evidence in this regard. In the same way, no evidence supports the
reliability of microcatheter FFR in the post-PCI assessment. Another current current gap in
knowledge is to demonstrate that the technical superiority, as compared to wire-based
systems, permits to apply a full physiology guided PCI in all anatomical and clinical
subsets.
Furthermore, a potential disadvantage is that the microcatheter may increase the degree of
coronary artery stenosis and affects the measured FFR value. The influence of the
microcatheter on coronary hemodynamic may also be lesion dependent and the small amount of
available data might not be translated across a spectrum of vessel and lesion types. A large,
dedicated, randomized trial is needed to overcome these issues.
Solid data coming from large randomized controlled trials about microcatheter technology are
missing in literature. To date, three studies have been published comparing FFR measured with
pressure microcatheter to FFR measured with a pressure wire.
The AQVA-II trial is a program of two nested, randomized, multicenter, open-label trials in
Italy. AQVA-II strategy compares longitudinal FFR- versus conventional angiography guided
PCI. AQVA-II physiology compares microcatheter- versus angiography-derived FFR guidance.
The primary outcome for AQVA-II strategy is post-PCI FFR >0.86 (superiority). The primary
outcome for the AQVA-II physiology is the post-PCI FFR value (non-inferiority).
The Sponsor of the study is U.O. Cardiologia, Azienda Ospedaliero Universitaria di Ferrara.
Coordinating center will be the Ferrara University Hospital.
Institutional review board will be obtained in all participating centers. The AQVA trial will
be performed in Ferrara University Hospital, Ferrara, Italy. Any additional site
participating in the trial will be reported on the website in the dedicated area. The
Executive Committee of the Study is composed by Simone Biscaglia (Principal Investigator),
Gianluca Campo (Study Chair), Carlo Penzo, Carlo Tumscitz, Andrea Erriquez. The statistical
analysis will be performed by the Centre for Epidemiology and Statistics of the University of
Ferrara (Elisa Maietti, Stefano Volpato).
