The FAVOR V AMI Trial

Not Applicable

Not yet recruiting

• Conditions: ST-Segment Elevation Myocardial Infarction; Multivessel Coronary Artery Disease; Percutaneous Coronary Intervention
• Interventions: Diagnostic Test: FAST Technique; Diagnostic Test: Angiography

• Registration Number: NCT05669222
• Lead Sponsor: China National Center for Cardiovascular Diseases

Brief Summary

The FAVOR V AMI study is a prospective, multicenter, blinded, randomized, sham-controlled trial comparing the long-term clinical outcomes of the "Functional and Angiography-derived Strain inTegration (FAST)" technique (next-generation quantitative flow ratio \[μQFR\] and radial wall strain \[RWS\]) guided percutaneous coronary intervention (PCI) strategy, with standard treatment strategy, in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD).

Detailed Description

The FAVOR V AMI study is a prospective, multicenter, blinded, randomized, sham-controlled trial comparing the long-term clinical outcome of the two PCI strategies, the FAST guided strategy (test group) versus standard treatment strategy (control group), in a high-risk population with STEMI and MVD who underwent successful primary PCI of the infarct-related artery. The primary endpoint is major adverse cardiac events (MACE), defined as a composite of all-cause death, myocardial infarction (MI), or ischemia-driven revascularization when the last patient reaches 6-month follow-up. The major secondary endpoint is cardiovascular death and MI when at least 395 total events have accrued. The study hypothesis is the FAST (μQFR+RWS) guided PCI strategy is superior to a standard treatment strategy by the primary and major secondary endpoint.

For the patients randomized to μQFR+RWS group, μQFR will be measured in all non-infarct related arteries containing any non-culprit lesion with visually-assessed percentage diameter stenosis (DS%) ≥50% and ≤90% with reference vessel diameter (RVD) ≥2.5 mm. If μQFR ≤0.80 or RWS ≥13%, PCI will be performed; if μQFR \>0.80 and RWS \<13%, the procedure will deferral; if DS% \>90%, PCI should be performed without the need of μQFR or RWS. For all patients undergoing PCI, post-PCI μQFR measurement is recommended; if μQFR \<0.90, if the reason is obvious post-dilation with a non-compliant balloon or bail-out stenting should be considered; if the reason is not obvious intravascular imaging should be considered. For the patients randomized to standard treatment group, PCI should be performed of all non-culprit lesions with visual DS% ≥70% in all non-infarct related arteries with RVD ≥2.5 mm; for a non-culprit lesion with visually DS% 50-70%, PCI can be performed if fractional flow reserve (FFR) ≤0.80 or instantaneous wave-free ratio (iFR) ≤0.89. All patients will be followed by either telephone or clinic visit at 1 month, 6 months,1 year, 2 years, 3 years, 4 years and 5 years.

The sample size will be about 5,000 using an event-driven sample calculation. An adaptive design will be implemented for sample size re-estimation when 90% of patients have been enrolled. All principal analyses will take place in the intention-to-treat (ITT) population. The primary and major secondary endpoints will be analyzed in prespecified subgroups, including age (≥65 vs. \<65), sex (men vs. women), diabetes (yes vs. no), time from symptom onset to primary PCI (≤ vs. \> median), planned number of NCLs for PCI in the control arm (0/1 vs. 2 vs. 3), infarct related artery (LM/LAD vs, others), untreated CTOs with RVD ≥2.5 mm in non-infarct related artery (yes vs. no), timing of elective PCI (same hospitalization as the emergency PCI vs. during an elective readmission), P2Y12 inhibitor therapy (Clopidogrel vs. Ticagrelor), treatment of any non-infarct lesion with DS \>90% prior to randomization (yes vs. no), LVEF (echo post primary PCI, prior to randomization) (\>40% vs. ≤40%), Killip Class (I vs. ≥II), lesion location of non-culprit lesion (LM/LAD vs. others), diseased vessels (two-vessel disease vs. LM/three-vessel disease), moderate or severe calcification in any NCL (yes vs. no), bifurcation lesion with planned main vessel and SB treatment in any NCL (yes vs. no), intravascular guidance during the randomized procedure (yes vs. no), μQFR grayzone (μQFR \< 0.75 vs. = 0.75-0.85 vs. \> 0.85 \[by core laboratory\]), μQFR-based functional SYNTAX score (FSSQFR, low tertile vs. mid tertile vs. high tertile \[by core laboratory\]), post-PCI μQFR (≥0.90 vs. \<0.90 \[by core laboratory\]), angiography-derived IMR (≥2.5 mmHgs/cm vs. \<2.5 mmHgs/cm \[by core laboratory\]), residual physiology pattern (PPG diffuse vs. local \[by core laboratory\]), μQFR-based residual functional SYNTAX score (rFSSQFR, 0 vs. ≥ 1 \[by core laboratory\]), learning experience of μQFR/RWS (first half vs. second half of enrolled cases in each center).

Study Timeline

• Study First Submitted: 2022-12-18
• Study First Submitted QC: 2022-12-27
• Study First Posted: 2022-12-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-10
• Last Update Posted: 2023-09-13
• Study Start: 2023-09-30
• Primary Completion: 2025-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 5000

Inclusion Criteria

• General inclusion

  1. Age ≥18 years
  2. STEMI ≤30d
  3. Successful primary PCI of all culprit lesion(s) responsible for the STEMI (visually-assessed residual stenosis <30% in stent-treated lesions or <50% in DCB-treated or PTCA-treated lesions, with TIMI-3 flow in all treated vessels)
  4. No MACE event between the index PCI and the staged randomized procedure
  5. Able to understand the trial design and provide written informed consent

• Angiographic inclusion:

  1. The presence of at least 1 non-culprit lesion with DS% 50%-90% in any non-infarct related artery with RVD ≥2.5 mm by visual assessment
  2. Non-culprit lesions are potentially eligible for PCI Note: All lesions in the infarct related arteries with DS ≥70% and RVD ≥2.5 mm by visual assessment must be successfully treated either during the index primary PCI or the staged procedure prior to randomization Note: There may also be 1 or more NCL with DS% >90% (including a CTO) as long as there is at least 1 NCL with DS% 50%-90% as above. Any such lesions in which PCI is intended must be treated successfully either during the index primary PCI or the staged procedure prior to randomization.

Exclusion Criteria

• General exclusion

  1. Cardiogenic shock or refractory hypotension (Killip IV)
  2. On pressors or use of or need for intra-aortic balloon pump or other mechanical circulatory support devices
  3. Intubated
  4. Prior thrombolytic therapy for this admission
  5. Cockcroft-Gault-calculated CrCl <30 ml/kg
  6. Pregnant or woman of child-bearing potential
  7. Life expectancy less than 1 year for non-cardiac causes
  8. Allergy to iodine-containing contrast agents which cannot be adequately premedicated
  9. Unable to tolerate DAPT for at least 6 months
  10. Prior CABG or planned CABG
  11. Any planned surgery within 6 months
  12. Any condition that may interfere with any follow-up procedures (e.g. dementia, drug use)

• Angiographic exclusion

  1. Poor angiographic image quality precluding vessel contour detection or with suboptimal contrast opacification, branch ostium cannot be shown clearly, severe overlap in the stenosed segment or severe tortuosity of any interrogated vessel deemed not amenable to μQFR or RWS measurement
  2. Unable to judge culprit lesion or infarct-related artery according to current evidence

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FAST Guided Strategy (μQFR+RWS)	Angiography	1. μQFR is measured in all non-infarct related arteries containing any non-culprit lesion with visually-assessed DS% ≥50% and ≤90% with RVD ≥2.5 mm. 1. μQFR ≤0.80: PCI 2. RWS ≥13%: PCI 3. μQFR \>0.80 and RWS \<13%: Deferral 4. DS% \>90%: PCI without the need of μQFR or RWS 2. For all patients undergoing PCI, post-PCI μQFR measurement is recommended; if μQFR \<0.90, if the reason is obvious post-dilation with a non-compliant balloon or bail-out stenting should be considered; if the reason is not obvious intravascular imaging should be considered.
FAST Guided Strategy (μQFR+RWS)	FAST Technique	1. μQFR is measured in all non-infarct related arteries containing any non-culprit lesion with visually-assessed DS% ≥50% and ≤90% with RVD ≥2.5 mm. 1. μQFR ≤0.80: PCI 2. RWS ≥13%: PCI 3. μQFR \>0.80 and RWS \<13%: Deferral 4. DS% \>90%: PCI without the need of μQFR or RWS 2. For all patients undergoing PCI, post-PCI μQFR measurement is recommended; if μQFR \<0.90, if the reason is obvious post-dilation with a non-compliant balloon or bail-out stenting should be considered; if the reason is not obvious intravascular imaging should be considered.
Standard Treatment Strategy	Angiography	1. PCI should be performed of all non-culprit lesions with visual DS% ≥70% in all non-infarct related arteries with RVD ≥2.5 mm; 2. For a non-culprit lesion with visually DS% 50-70%, PCI can be performed if FFR ≤0.80 or iFR ≤0.89.

Primary Outcome Measures

Name	Time	Method
Incidence of major adverse cardiac events (MACE)	From the date of first randomization until a total number of 395 events of MACE is reached (median follow-up of approximately 1.5 years)	Defined as a composite of all-cause death, myocardial infarction (MI), or ischemia-driven revascularization

Secondary Outcome Measures

Name	Time	Method
Incidence of cardiovascular death and MI (Major secondary endpoint）	From the date of first randomization until a total number of 395 events of cardiovascular death and MI is reached (median follow-up of approximately 3 years)	Defined as a composite of cardiovascular death and MI
Rate of procedural success	Maximum of 7 days	Defined as lesion success in all treated lesions without in-hospital MACE
Incidence of definite/probable stent thrombosis (ARC-2)	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years	By ARC-2 definition and including acute, subacute, late and very late stent thrombosis
Angina status evaluation	6 months, 1 year, 3 years, 5 years	As assessed by the Seattle Angina Questionnaire (SAQ)
Incidence of all MI	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years	Including periprocedural MI (SCAI definition) and spontaneous MI (target vessel-related or non-target vessel-related, culprit lesion-related or non-culprit lesion-related)
Health-related quality of life evaluation	6 months, 1 year, 3 years, 5 years	As assessed by the European Quality of Life-5 Dimensions (EQ-5D)
Cost-utility evaluation	6 months, 1 year, 3 years, 5 years	As assessed by the Incremental cost-utility ratio (ICUR) using quality-adjusted life years (QALYs)
Rate of lesion success	Immediately post the PCI procedure	Defined as: 1) angiographic success (core laboratory-assessed residual stenosis \<30% in stent-treated lesions or \<50% in DCB-treated or PTCA-treated lesions, with TIMI-3 flow in the treated vessel); and 2) physiological success (post-PCI μQFR ≥0.80 assessed by core lab)
Cost-effectiveness evaluation	6 months, 1 year, 3 years, 5 years	As assessed by the Incremental cost effectiveness ratio (ICER) using the composite endpoint (including myocardial infarction, any revascularization, stent thrombosis, cerebrovascular and major bleeding events)
Incidence of death	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years	Including cardiovascular, non-cardiovascular or undetermined
Incidence of any revascularization	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years	Including ischemia-driven or non-ischemia driven, target vessel-related or non-target vessel-related, culprit lesion-related or non-culprit lesion-related