The FAVOR V AMI Trial

Percutaneous Coronary Intervention Clinical Trial

Official title:

Functional and Angiography-Derived Strain Guided Multi-Vessel/Lesion Revascularization Strategy in Patients With Acute ST-Segment Elevation Myocardial Infarction (FAVOR V AMI)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05669222
• Other study ID #: FAVOR V AMI
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 30, 2023
• Est. completion date: June 2028

Study information

• Verified date: September 2023
• Source: China National Center for Cardiovascular Diseases
• Contact: Bo Xu, MBBS
• Phone: +86-10-88322562
• Email: bxu[@]citmd.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 5000
• Est. completion date: June 2028
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Infarction
• Multivessel Coronary Artery Disease
• Myocardial Infarction
• Myocardial Ischemia
• Percutaneous Coronary Intervention
• ST Elevation Myocardial Infarction
• ST-Segment Elevation Myocardial Infarction

Intervention

Diagnostic Test:
• FAST Technique
The next-generation QFR (µQFR) introduces a more intelligent algorithm and supports single-projection rapid calculation with a diagnostic accuracy of 93.0% compared with FFR; Computational RWS technique facilitates the assessment of lesion vulnerability.
• Angiography
Coronary angiography is a procedure that uses contrast under x-ray pictures to detect stenosis in the coronary arteries.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
China National Center for Cardiovascular Diseases

References & Publications (7)

Erlinge D, Maehara A, Ben-Yehuda O, Botker HE, Maeng M, Kjoller-Hansen L, Engstrom T, Matsumura M, Crowley A, Dressler O, Mintz GS, Frobert O, Persson J, Wiseth R, Larsen AI, Okkels Jensen L, Nordrehaug JE, Bleie O, Omerovic E, Held C, James SK, Ali ZA, Muller JE, Stone GW; PROSPECT II Investigators. Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study. Lancet. 2021 Mar 13;397(10278):985-995. doi: 10.1016/S0140-6736(21)00249-X. — View Citation

Hong H, Li C, Gutierrez-Chico JL, Wang Z, Huang J, Chu M, Kubo T, Chen L, Wijns W, Tu S. Radial wall strain: a novel angiographic measure of plaque composition and vulnerability. EuroIntervention. 2022 Sep 8;18(12):1001-10. doi: 10.4244/EIJ-D-22-00537. Online ahead of print. — View Citation

Mehta SR, Wood DA, Storey RF, Mehran R, Bainey KR, Nguyen H, Meeks B, Di Pasquale G, Lopez-Sendon J, Faxon DP, Mauri L, Rao SV, Feldman L, Steg PG, Avezum A, Sheth T, Pinilla-Echeverri N, Moreno R, Campo G, Wrigley B, Kedev S, Sutton A, Oliver R, Rodes-Cabau J, Stankovic G, Welsh R, Lavi S, Cantor WJ, Wang J, Nakamya J, Bangdiwala SI, Cairns JA; COMPLETE Trial Steering Committee and Investigators. Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med. 2019 Oct 10;381(15):1411-1421. doi: 10.1056/NEJMoa1907775. Epub 2019 Sep 1. — View Citation

Puymirat E, Cayla G, Simon T, Steg PG, Montalescot G, Durand-Zaleski I, le Bras A, Gallet R, Khalife K, Morelle JF, Motreff P, Lemesle G, Dillinger JG, Lhermusier T, Silvain J, Roule V, Labeque JN, Range G, Ducrocq G, Cottin Y, Blanchard D, Charles Nelson A, De Bruyne B, Chatellier G, Danchin N; FLOWER-MI Study Investigators. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021 Jul 22;385(4):297-308. doi: 10.1056/NEJMoa2104650. Epub 2021 May 16. — View Citation

Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serruys PW; PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011 Jan 20;364(3):226-35. doi: 10.1056/NEJMoa1002358. Erratum In: N Engl J Med. 2011 Nov 24;365(21):2040. — View Citation

Tu S, Ding D, Chang Y, Li C, Wijns W, Xu B. Diagnostic accuracy of quantitative flow ratio for assessment of coronary stenosis significance from a single angiographic view: A novel method based on bifurcation fractal law. Catheter Cardiovasc Interv. 2021 May 1;97 Suppl 2:1040-1047. doi: 10.1002/ccd.29592. Epub 2021 Mar 4. — View Citation

Xu B, Tu S, Song L, Jin Z, Yu B, Fu G, Zhou Y, Wang J, Chen Y, Pu J, Chen L, Qu X, Yang J, Liu X, Guo L, Shen C, Zhang Y, Zhang Q, Pan H, Fu X, Liu J, Zhao Y, Escaned J, Wang Y, Fearon WF, Dou K, Kirtane AJ, Wu Y, Serruys PW, Yang W, Wijns W, Guan C, Leon MB, Qiao S, Stone GW; FAVOR III China study group. Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet. 2021 Dec 11;398(10317):2149-2159. doi: 10.1016/S0140-6736(21)02248-0. Epub 2021 Nov 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of major adverse cardiac events (MACE)	Defined as a composite of all-cause death, myocardial infarction (MI), or ischemia-driven revascularization	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)
Secondary	Incidence of cardiovascular death and MI (Major secondary endpoint)	Defined as a composite of cardiovascular death and MI	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)
Secondary	Rate of lesion success	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)	Immediately post the PCI procedure
Secondary	Rate of procedural success	Defined as lesion success in all treated lesions without in-hospital MACE	Maximum of 7 days
Secondary	Incidence of death	Including cardiovascular, non-cardiovascular or undetermined	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Incidence of all MI	Including periprocedural MI (SCAI definition) and spontaneous MI (target vessel-related or non-target vessel-related, culprit lesion-related or non-culprit lesion-related)	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Incidence of any revascularization	Including ischemia-driven or non-ischemia driven, target vessel-related or non-target vessel-related, culprit lesion-related or non-culprit lesion-related	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Incidence of definite/probable stent thrombosis (ARC-2)	By ARC-2 definition and including acute, subacute, late and very late stent thrombosis	30 days, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Angina status evaluation	As assessed by the Seattle Angina Questionnaire (SAQ)	6 months, 1 year, 3 years, 5 years
Secondary	Health-related quality of life evaluation	As assessed by the European Quality of Life-5 Dimensions (EQ-5D)	6 months, 1 year, 3 years, 5 years
Secondary	Cost-effectiveness evaluation	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)	6 months, 1 year, 3 years, 5 years
Secondary	Cost-utility evaluation	As assessed by the Incremental cost-utility ratio (ICUR) using quality-adjusted life years (QALYs)	6 months, 1 year, 3 years, 5 years