FFR-Guided PCI vs CABG for Coronary Artery Disease

(FAME 3 Trial)

Not currently recruiting at 48 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Pregnancy, Recent STEMI, Low ejection fraction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatments for coronary artery disease (CAD), a condition where heart arteries narrow. It compares a special heart procedure using a pressure wire, called FFR-guided PCI (a minimally invasive procedure), to the traditional heart surgery known as CABG (Coronary Artery Bypass Grafting). The researchers aim to determine if these treatments yield similar outcomes for patients with multiple blocked heart vessels. Individuals experiencing chest pain and confirmed significant blockages in three heart arteries might qualify for this trial. As an unphased trial, it offers patients the chance to contribute to valuable research that could enhance treatment options for CAD.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that FFR-guided PCI, a technique using a special wire to measure blood pressure in heart arteries, is generally safe for patients with multiple blocked arteries. Studies have found that this treatment has similar rates of death and stroke compared to coronary artery bypass graft surgery (CABG), a more traditional method. However, one study noted that while FFR-guided PCI is safe, it may not be as effective as CABG in preventing future heart issues like heart attacks or the need for additional procedures.

Another study confirmed the long-term safety of FFR-guided PCI, especially for patients with severely narrowed arteries. These findings suggest that while FFR-guided PCI is safe, it might not fully replace CABG in all cases due to differences in long-term results.

CABG has been a standard procedure for many years and is well understood in terms of safety. Both treatments have their pros and cons, but FFR-guided PCI is generally well-tolerated by patients in terms of immediate safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for coronary artery disease because they offer new approaches to managing blocked arteries. Unlike standard care, which typically involves either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with stenting, this trial compares the effectiveness of a special technique called FFR-guided PCI to traditional CABG. FFR-guided PCI uses a pressure wire to measure the severity of blood flow blockages, allowing for more targeted stent placement only when necessary, potentially reducing unnecessary procedures. CABG, on the other hand, remains a reliable option, offering complete arterial revascularization, which can provide long-term benefits. By examining these two methods side by side, researchers hope to determine which approach provides better outcomes for patients, tailoring treatments more precisely to individual needs.

What evidence suggests that this trial's treatments could be effective for coronary artery disease?

This trial will compare Fractional Flow Reserve (FFR)-guided Percutaneous Coronary Intervention (PCI) with Coronary Artery Bypass Grafting (CABG) for patients with multiple blocked heart arteries. Studies have shown that both FFR-guided PCI and CABG result in similar rates of death and stroke. After five years, researchers found no significant difference in the risk of death, stroke, or heart attack between the two treatments. Additionally, using FFR to guide PCI can lead to better long-term results and may be more cost-effective than using medication alone. This suggests that FFR-guided PCI is an effective treatment option for people with multiple blocked heart arteries. ^{1 3 6 7 8}

Who Is on the Research Team?

Nico HJ Pijls, MD, PhD

Principal Investigator

Catharina Hospital Eindhoven, The Netherlands

Bernard De Bruyne, MD, PhD

Principal Investigator

VZW Cardiovascular Research Center Aalst

William F Fearon, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults over 21 with multivessel coronary artery disease, which means they have significant blockages in all three major heart arteries but not the main left one. They must be experiencing chest pain or signs of poor blood flow to the heart and can undergo either stent placement or bypass surgery. Excluded are those with recent severe heart attacks, very weak hearts, short life expectancy, kidney failure requiring dialysis, planned organ transplants, pregnancy, or inability to take blood-thinning drugs for six months.

Inclusion Criteria

I have blockages in three major heart arteries but not the main one, treatable by surgery or stenting.

I am 21 or older with chest pain or signs of heart muscle issues.

Willing and able to provide informed, written consent

Exclusion Criteria

I need dialysis for my kidneys.

My stent in a blood vessel has narrowed again.

I cannot take dual antiplatelet therapy for six months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either FFR-guided PCI or CABG based on randomization

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 1 and 6 months, and 1, 3, and 5 years

What Are the Treatments Tested in This Trial?

Interventions

• CABG
• FFR guided PCI
• Resolute Integrity Stent
• Resolute Onyx Stent

Trial Overview The study compares two ways to improve blood flow in patients with blocked arteries: FFR-guided PCI (a procedure where a wire measures blood pressure differences across a blockage to guide stent placement) versus traditional bypass surgery (CABG). It aims to see if using FFR measurements before placing stents results in similar health outcomes as bypass surgery.

How Is the Trial Designed?

Group I: FFR guided PCI Active Control 3 Interventions

Patients undergoing PCI will have FFR measured with a St. Jude Medical coronary pressure wire across all lesions. If the FFR is ≤0.80, then PCI will be performed with the Medtronic Resolute Integrity (or Onyx) drug-eluting stent (DES) as per usual routine. If the FFR is \>0.80 then PCI will be deferred. Only those sites with prior experience measuring FFR will be included in the FAME 3 trial. These patients in whom FFR of a particular lesion was not possible will be included in all analyses based on the intention to treat principle.

Group II: CABG Active Control 1 Intervention

CABG will be performed as per clinical routine at each participating center. Both off-pump and on-pump surgery are acceptable, as long as the surgeon and the site are experienced in the particular technique. An internal mammary graft to the LAD should be attempted in all cases, if feasible. Complete arterial revascularization is strongly recommended, however, each center should use a conduit strategy with which they are most comfortable. All vessels ≥ 1,5 mm in diameter and with ≥ 50% stenosis should be bypassed, if technically feasible.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Golden Jubilee National Hospital

Collaborator

Trials

48

Recruited

14,200+

Genae

Industry Sponsor

Trials

9

Recruited

2,300+

Catharina Ziekenhuis Eindhoven

Collaborator

Trials

154

Recruited

130,000+

University of California, Irvine

Collaborator

Trials

580

Recruited

4,943,000+

Houston Methodist DeBakey Heart and Vascular Center, Houston

Collaborator

Trials

1

Recruited

1,500+

King's College Hospital NHS Trust

Collaborator

Trials

267

Recruited

505,000+

Houston Methodist DeBakey Heart & Vascular Center

Collaborator

Trials

1

Recruited

1,500+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

VZW Cardiovascular Research Center Aalst

Collaborator

Trials

11

Recruited

9,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41024968/

Fractional flow reserve guided percutaneous coronary ... FFR-guided PCI and CABG have similar rates of all-cause mortality and stroke in patients with multivessel CAD. However, CABG results in ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2112299

Fractional Flow Reserve–Guided PCI as Compared with ... Large, randomized trials have shown improved outcomes in patients with three-vessel coronary artery disease when coronary revascularization is ...

3. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00505-7/abstract

Outcomes after fractional flow reserve-guided ... Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625005057

Articles Outcomes after fractional flow reserve-guided ... At the 5-year follow-up, there was no significant difference in a composite outcome of death, stroke, or myocardial infarction after FFR-guided PCI versus CABG.

5. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.031907

Clinical Outcomes and Cost-Effectiveness of Fractional ... PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6503473/

Long-term outcomes after fractional flow reserve-guided ... To explore the safety and efficacy of FFR-guided percutaneous coronary intervention (PCI) in vessels with severe diameter stenosis.

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01132495

Study Details | NCT01132495 | FAME II The overall purpose of the FAME II trial is to compare the clinical outcomes, safety and cost-effectiveness of FFR-guided PCI plus optimal medical treatment ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1443950621000743

Safety and Long-Term Clinical Outcomes of Fractional ... This observational study highlights the safety and long-term effectiveness of FFR-guided coronary revascularisation in patients with predominantly stable ...