Clinical trial NCT04259853: Quantitative Fractional Ratio-guided Revascularization in STEMI Patients With Multi-vessel Disease
Official title: Quantitative Fractional Ratio-guided Non-culprit-vessel Revascularization in STEMI Patients With Multi-vessel Disease: a Prospective Multi-center Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: ST Elevation Myocardial Infarction
Multi-Vessel Coronary Artery Stenosis
Keywords: ST Elevation Myocardial Infarction
Multi-Vessel Coronary Artery Stenosis
Coronary physiological function
Quantitative fractional ratio
Percutaneous coronary intervention
Lead sponsor: Fujian Medical University
Sponsor class: OTHER
Collaborators: name: Pulse Medical Imaging Technology (Shanghai) Co., Ltd
First posted: 2020-02-07
Enrollment: 1016
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: About half of patients with ST-segment elevation myocardial infarction (STEMI) have multi-vessel lesions (\> 50% diameter stenosis). But how to deal with the non-culprit vessels is still controversial. Previous studies have shown that flow fractional reserve (FFR)-guided revascularization on non-culprit vessels can further improve prognosis of such patients. However, FFR requires the use of pressure guidewire and special drugs such as adenosine to maximize induction of hyperemia forcoronary artery, which will increase the cost of operation and may cause additional risks. Quantitative flow ratio (QFR) is a novel angiography-based method for deriving FFR without pressure wire or induction of hyperemia. In present, there still are poor data about QFR-guided revascularization on non-culprit vessels in patients with STEMI. The purpose of this study is to compare the clinical effects of QFR-guided with angiography-guided revascularization on non-culprit vessel in STEMI patients with multi-vessel lesions.

Detailed description: 41% -67% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenosis in non-culprit vessels (\> 50% diameter stenosis). Compared with patients with single-vessel lesion, these patients with multi-vessel disease have a worse survival rate after percutaneous coronary intervention (PCI). Previous studies have shown that they not only receive more revascularization than the latter but also have a higher incidence of heart failure and more frequent electrical instability after myocardial infarction.

Early guidelines from European Society of Cardiology and the American College of Cardiology/American Heart Association discourage treating the non-culprit vessels in the acute phase. However, these recommendations are given mainly based on some small-sample retrospective studies.

With the use of second-generation drug-eluting stents and novel antithrombotic drugs, the clinical benefits from primary PCI and elective PCI have been greatly improved. Results from some small-sample prospective randomized studies have demonstrated that complete revascularization on STEMI patients with multi-vessel diseases is superior to a strategy of culprit-only revascularization. Especially, more recent two trials (PRAMI and CVLPRIT) further confirmed that complete revascularization in the acute phase can produce beneficial clinical results compared to culprit-only revascularization. However, stenting for these lesions in the two studies was decided based on angiographic findings regardless of whether the lesion caused myocardial ischemia or symptoms. Moreover, coronary angiography may underestimate and overestimate the functional severity of the lesion. Stent implantation preventively will lead to overtreatment, increasing additional cost and risk. Finally, not all such studies demonstrated positive findings. For example, the PRAGUE-13 study comparing angiography-guided complete revascularization with culprit-only treatment did not find that complete revascularization has more advantages. Therefore, the angiography-guided strategy for complete revascularization in STEMI patients with multi-vessel lesions remains questionable.

The clinical value of flow fractional reserve (FFR) as a gold standard for the assessment of coronary function in ischemia has been well confirmed in coronary intervention. Recently, three studies based on coronary functioning have shown that FFR-guided complete revascularization is superior to the strategy of only treating culprit lesion. However, clinical benefit of FFR is mainly from reducing the incidence of subsequent revascularization but not hard endpoints such as death. On the other hand, the time of treatment for non-culprit vessel was not completely consistent and not all patients in the FFR group received FFR measurements in these studies. Heterogeneities from these studies may weaken the clinical benefit of FFR in guiding complete revascularization in STEMI patients. Although the current guidelines recommend that non-culprit lesions be allowed for treatment when emergency PCI is performed on specific patients (Class IIa, Level A), it is still necessary to conduct studies targeted on these issues to further clarify the value of coronary functional approach in revascularization on non-culprit vessel of patients with STEMI. FFR also has certain limitations: first, FFR is an invasive test, which requires a pressure guide wire, in turn inevitably increases the cost of operation and may cause additional procedure-associated risks; secondly, drugs such as adenosine are required to maximize hyperemia of coronary artery, and these adverse drug reactions may increase the incidence of adverse clinical events, especially in the acute state of myocardial infarction.

Quantitative flow ratio (QFR) is a novel angiography-based method accurate assessing coronary physiological functions for deriving FFR without the use of pressure wire and induction of hyperemia. The three-dimensional reconstruction of the coronary arteries is performed through two angiographic images with an acquisition angle difference of \> 25 °. The QFR value is finally calculated based on the flow velocity obtained by a method of frame rate counting. In the past five years, a vast number of studies confirmed QFR is highly consistent with FFR in the diagnosis of myocardial ischemia, and the diagnostic accuracy of QFR is significantly higher than that of quantitative coronary angiography. Recent studies have also shown that, compared with conventional angiography-guided PCI, QFR-guided PCI for patients with stable angina pectoris has significantly reduced adverse cardiovascular events such as death and revascularization. Especially, QFR and FFR can accurately assess the coronary physiological function status of non-culprit lesions in emergency PCI patients, and its effectiveness is consistent with FFR applied to patients with stable coronary heart disease. Although previous studies provided the theoretical support, there are still poor data on QFR-guided non-culprit revascularization on STEMI patients with multi-vessel disease. Thus, we hypothesized that strategies for QFR to assess all blood flow limiting lesions and guide revascularization during emergency PCI would lead to better short-term and long-term clinical outcomes for STEMI patients with multiple vessel lesions, including improved left ventricular function, less secondary revascularization, less frequency of hospitalization, lower medical costs.

Eligibility criteria: Inclusion Criteria:

* Suitable for emergency PCI within 12 hours;
* At least one lesion with a stenosis of 50% - 90% in the non culprit vessel and PCI required by the operator.
* Voluntary acceptance of all follow-up assessments required by the protocol.
* The subject (or legal guardian) who understands the protocol requirements and treatment procedures, and signs a written informed consent before performing the examination or operation specified in the scheme.

Exclusion Criteria:

* Left main lesion (a stenosis of ≥ 50%).
* STEMI caused by stent thrombosis.
* Non culprit vessels are chronic occlusive disease (CTO).
* The anatomy of non culprit vessels not suitable for PCI.
* The TIMI flow of non culprit vessels less than grade 2.
* Patients with one of the following conditions in the treatment of infarct related vessel:

  1. Coronary artery perforation.
  2. After the treatment, there is permanent no reflow (TIMI 0-1).
  3. The stent could not be implanted.
* Patients with Killip grade III-IV who can still not tolerate PCI again after treated for one week.
* Known severe cardiac valve dysfunction requiring surgery during follow-up.
* Subjects could not tolerate dual-antiplatelet therapy.
* Woman with pregnancy or planning to pregnancy.
* Patients with known allergy to the study stent system (sirolimus, everolimus, zotarolimus) or to protocol-required concomitant medications
* Patients participating any other clinical trials.
* Expected the patients who can not be followed up regularly according to the protocol or lost during the follow-up.

Primary outcomes:
measure: NACE (Net Adverse Clinical Events)
timeFrame: 12 months
Secondary outcomes:
measure: 2-year NACE
timeFrame: 24 months
measure: 3-year NACE
timeFrame: 36 months
measure: MACE (Major Adverse Cardiovascular Events)
timeFrame: up to 36 months
Other outcomes:
measure: Stent thrombosis
timeFrame: up to 36 months
measure: Major bleeding
timeFrame: up to 36 months
measure: Stroke
timeFrame: up to 36 months
measure: Cost-effective assessment
timeFrame: up to 12 months
Locations:
city: Fuqing
country: China
facility: Fuqing Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian provincial hospital
state: Fujian
city: Fuzhou
country: China
facility: The First Hospital of Fuzhou City
state: Fujian
city: Longyan
country: China
facility: The First Hospital of Longyan City
state: Fujian
city: Ningde
country: China
facility: Ningde Hospital Affiliated to Ningde Normal University
state: Fujian
city: Putian
country: China
facility: Putian Colloge affiliated Hospital
state: Fujian
city: Putian
country: China
facility: The First Hospital of Putian City
state: Fujian
city: Quanzhou
country: China
facility: The Second Affiliated Hospital of Fujian Medical University
state: Fujian
city: Quanzhou
country: China
facility: QUANZHOU First Hospital
state: Fujian
city: Sanming
country: China
facility: Sanming First Hospital
state: Fujian
city: Shaowu
country: China
facility: Hospital of Shaowu city
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Affiliated to Xiamen University
state: Fujian
city: Zhangzhou
country: China
facility: Zhangzhou city's Hospital
state: Fujian
Study officials:
affiliation: Fujian Medical University
name: Lianglong Chen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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